RPOHuman Subjects ResearchIRB Policies and Procedures

 

Introduction

RPO staff have combined the IRB Operating Procedures and the Researcher Manual into one set of Operating Policies and Procedures. Please note that there are areas within the new document that reference the new Common Rule, which has been delayed until July 19, 2018. These areas are clearly identified and should not be referenced at this time. For updates to the Common Rule compliance date, please go to the Regulatory Changes web page.

 

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Table of Contents

 

Section I Committee Information

 

1. Committee Mission

The University of Vermont and UVM Medical Center are responsible for safeguarding the rights and welfare of human subjects involved in any research activity. According to institutional policy, all such research, funded or unfunded, conducted by University and/or UVM Medical Center personnel, including students, or done under the auspices or sponsorship of either institution must be reviewed by one of the Institutional Review Boards (IRBs): the Committee on Human Research in the Medical Sciences (CHRMS) or the Committee on Human Research in the Behavioral and Social Sciences (CHRBSS). Approval must be obtained BEFORE the research activity starts and the project must be reviewed at least annually for as long as it is active.

 

1.1 Introduction to the Boards (The Committees)

The Institutional Review Boards (IRBs) at the University of Vermont (UVM) serve UVM and the University of Vermont Medical Center (UVMMC). UVM and UVMMC each have their own Federalwide Assurances of Compliance with DHHS Regulations for the Protection of Human Subjects (FWA).

  • The “Committee on Human Research in the Medical Sciences" (CHRMS) is authorized to review all proposals to use human subjects in biomedical research. CHRMS also functions as the Privacy Board for UVMMC for the Health Insurance Portability and Accountability Act (HIPAA) by reviewing all authorizations or requests to waive authorization for research undertaken at both institutions.
  • The “Committee on Human Research in the Medical Sciences (CHRMS II), is a subset of the full committee (CHRMS) for situations where it is not practicable to convene the full CHRMS. This board is primarily used for compassionate use protocols.
  • The “Committee on Human Research in the Behavioral and Social Sciences" (CHRBSS) is authorized to review all proposals to use human subjects in the social sciences, education, psychology and other non-medical fields.
  • The Safety Subcommittee, which is a subset of the full Committees, reviews adverse events, protocol deviations, unanticipated problems involving risks to subjects or others, data and safety monitoring reports, and addendums to the protocol’s investigational drug/device brochure that may require further action.
  • Ad-hoc Noncompliance Subcommittees, including a subset of the members and other institutional personnel as applicable, are convened as necessary to review noncompliance cases.
  • The IRB Policy and Procedure Committee, which includes Committee leadership and IRB staff, convenes monthly to review changes in policy and procedures.
  • Additional subcommittees may be added as needed.

Purpose

The Committees have been established to review all research projects and activities involving human subjects in accordance with the Federalwide Assurances that both UVM and UVMMC have in place to ensure that the rights and welfare of those involved are adequately protected, that the methods used to obtain informed consent are adequate and appropriate, and that any risks to individuals are out-weighed by the potential benefit to them or by the general importance of the knowledge to be gained.

Governing Principles

The Committees are governed by the basic principles regarding experimentation on humans which have their origins in the Nuremberg Code, the Belmont Report, and the Declaration of Helsinki and are consistent with the regulations governing research with human subjects, i.e., 45 CFR 46 of the Code of Federal Regulations (and __CFR__, the Federal Policy for the Protection of Human Subjects) and for FDA regulated clinical trials, the applicable sections of the CFR (usually 21 CFR 50 and 21 CFR 56).

Federalwide Assurance

UVM and UVMMC each have established Federalwide Assurances with the Department of Health and Human Services (DHHS) that commits the institutions to comply with the requirements in the HHS Protection of Human Subjects regulations at 45 CFR part 46.

The FWAs for UVM and UVMMC are limited in applicability to federally sponsored or conducted research. In general, however, UVM and UVMMC extend the principles of the regulations governing research with human subjects to research not federally sponsored or conducted. The IRB reserves the right to review any other research involving human subjects not otherwise covered by the FWA that is conducted at UVM or UVMMC facilities.

Prompt reporting for all research conducted or supported by any federal department or agency will take place in accordance with the regulations governing research with human subjects, i.e., 45 CFR 46 of the Code of Federal Regulations and for FDA regulated clinical trials, the applicable sections of the CFR 21 CFR 50 and 21 CFR 56.

The University is not required in Sec.__.103(b)(2) to designate one or more IRBs on its FWA.

Committee Authority

The President of the University (UVM) has delegated the authority to the Vice President for Research as the lead Institutional Official (IO) responsible for the assurance of compliance in the area of human subject protections. The Committees are established by authority of the Vice President for Research. The Committees are delegated the specific authority to:

  • (UVM)Define the basic policies, procedures and standards by which human
    research protocols will be reviewed;
  • Sec. __109(a)Review and have authority to approve, require modifications in, or disapprove all research activities, including exempt research activities under Sec. __.104 for which limited IRB review is a condition of exemption
  • Sec. __109 (b)Require that information given to subjects (or legally authorized representatives, when appropriate) as part of informed consent is in accordance with Sec. __.116. The IRB may require that information, in addition to that specifically mentioned in the regulations, be given to the subject when, in the IRB's judgement, the information would meaningfully add to the protection of the rights and welfare of subjects.
  • Sec. __109 (c)Require documentation of informed consent or waive documentation in accordance with the regulations.
  • Sec. __109 (d) An IRB shall notify investigators and the institution in writing of its decision to approve or disapprove the proposed research activity, or of modifications required to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, it shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.
  • (UVM)Require that waivers or alterations of consent comply with the requirements outlined in the federal regulations.
  • Sec. __109 (e)Conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and research.

Post 2018 Common Rule Change – Disregard this bullet point

  • Sec. __109 (f)(1) Unless an IRB determines otherwise, continuing review of

research is not required in the following circumstances:

(i) Research eligible for expedited review in accordance with Sec.

__.110;

(ii) Research reviewed by the IRB in accordance with the limited

IRB review described in Sec. __.104(d)(2)(iii), (d)(3)(i)(C), or (d)(7) or (8);

(iii) Research that has progressed to the point that it involves

only one or both of the following, which are part of the IRB-approved study:

(A) Data analysis, including analysis of identifiable private

information or identifiable biospecimens, or

(B) Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

  • Sec. __109 (g)shall have authority to observe or have a third party observe the consent process and research.
  • Sec. __108 (4i)Investigate and report to the appropriate institutional officials, Office of Human Research, DHHS (OHRP), and, when applicable US Food and Drug Administration (FDA) and/or funding agency, any serious or continuing noncompliance with the federal regulations and requirements and determinations of the IRB.
  • Sec. __113 Suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall be reported promptly to the investigator, appropriate institutional officials, OHRP, and/or FDA when applicable.
  • (UVM)Provide training for all individuals involved in the conduct of research involving human subjects, regardless of funding source.
  • (UVM)Review all adverse events and unanticipated problems to subjects and others meeting local IRB criteria.
  • (UVM and UVMMC) Function as the Privacy Board by reviewing all HIPAA authorization language or requests to waive authorization for research undertaken at both UVM and UVM Medical Center.
  • Sec. __111 Monitor active projects to ensure compliance with the IRB-approved protocol and with applicable human subject protection guidelines and regulations.

The authority of the Committees to disapprove, restrict, suspend or terminate a human research study may not be overridden. However, the Vice President for Research will have the final authority to disapprove, restrict, suspend or terminate a study, which has received Committee approval.

Resources

(Sec. __108(a)(1)The institution will provide IRBs with resources, office space, professional staff, and support staff sufficient to carry out their responsibilities efficiently and effectively and to serve as day-to-day liaison with appropriate University administrative offices, project investigators, other institutional safety and ethics boards, and various regulatory and funding agencies.

Institutional Relationships

UVM is the institution associated with the IRB registrations for the Committees with the Office for Human Research Protections (OHRP) and has a written agreement with UVMMC for their reliance on UVM’s IRBs. The Research Protections Office (RPO) is responsible for completing the IRB registration in accordance with 21 CFR 56.106 and 45 CFR 46 subpart E. The Vice President for Research is the designated Institutional Official for research involving human subjects for UVM. The President and CEO of the University of Vermont Health Network at UVMMC is the Institutional Official for UVMMC. The Committees report to regulatory authorities (i.e., FDA, OHRP) through the institutional official(s) or his/her designee at UVM and/or UVMMC, as appropriate.

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1.2 Committee Membership (Sec. __.107)

The membership of the Committees meets all criteria required by the applicable regulations and guidelines governing research with human subjects. The Committees are constituted of members with varying backgrounds sufficiently qualified for review through appropriate experience and expertise. When membership decisions are made, consideration is given to gender, race, cultural backgrounds, and sensitivity to community attitudes.

Executive Chair

An Executive Chair for the Committees on Human Research in the Medical Sciences may be appointed by the Vice President for Research and may fulfill any or all of the responsibilities listed below.

The Executive Chair will have responsibilities to oversee policy development and implementation, regulatory issues, noncompliance cases, and consistency between the operations of the Medical Science IRBs. It is not intended for the Executive Chair to have the responsibility for routinely conducting IRB meetings.

Chair

  • Committee Chairs are appointed by the Vice President for Research.
  • A Committee Chair must be a University faculty member and must have prior service as a Committee member.
  • It is the responsibility of the Committee Chairs to conduct Committee meetings in accordance with established federal regulations and University operating policies and procedures. These responsibilities, which include but are not limited to the following, are to:
    • sign official Committee action documents and human subjects assurance forms;
    • keep abreast of relevant state and federal regulations;
    • meet as needed with the Executive Director of Research or the Vice President for Research to discuss Committee activities;
    • meet as needed with each other to coordinate the efforts of the Committees;
    • keep abreast of procedures for maintenance of official protocol files and other administrative operations of their respective Committees;
    • recommend, in consultation with the Executive Director of Research or the Director of the Research Protections Office, new members to the Vice President for Research;
    • ensure that new members are properly oriented to and educated about their duties and responsibilities;
    • initiate activities designed to assist investigators and keep the campus and community apprised of their rights and responsibilities with regard to human research; and
    • assist appropriate University administrators in the preparation of federal reports and assurances and meet with federal IRB auditors as necessary.
  • No method for removal is delineated, as all members are appointed and serve at the discretion of the Vice President for Research.
  • Appointment to the Chair will be for renewable two-year terms.

Associate Chair

  • The Associate Chair must be appointed from the regular voting membership to assist the Chairs, particularly in the conduct of expedited protocol review, and serve as acting Chair in his or her absence.
  • The Associate Chair of CHRMS will be one of the licensed physicians on the Committee if the Chair is not a licensed physician.

Regular Members

Members will be of varying professional and personal backgrounds and must demonstrate a genuine interest in and commitment to the purpose of the Committees. Specific membership criteria will comply with all relevant federal and state regulations. The Committee Members’ duties are delineated in subsequent sections.

  • The Executive Director of Research appoints all Committee Members, after receiving recommendations from the Committee Chairs.
  • When vacancies occur, nomination will be sought, after which formal recommendation(s) for new member(s) will be made by the Committee Chair to the Executive Director of Research. Every effort will be made to fulfill principles which embrace cultural diversity.
  • The Executive Director of Research will in no case make a final appointment without prior consultation with the Committee Chair or the Director of the Research Protections Office.
  • Committee appointments will usually be for renewable two-year terms, serving at the discretion of the Vice President for Research.
  • Consideration is given to achieve a balance between new and experienced members when determining which appointments will be renewed.
  • No specific attendance requirements are delineated, however it is required that committee members demonstrate a genuine interest and commitment to the purpose of the Committees.
  • No method for removal is delineated, as all members are appointed and serve at the discretion of the Vice President for Research.
  • (Sec.__107)(b) Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.
  • Sec.__107(c) Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.
  • Sec. __107(d) No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.
  • Sec. __107(e) An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB.

Ex Officio Members

An ex officio member is defined as a member who serves by virtue of an office or position held. An ex officio member may be appointed by the Institutional Official as a voting member, a non-voting member, or an alternate member.

Alternate Members

An alternate member is defined as a member who substitutes for a specific member or members with similar qualifications, experience or membership category.

  • Alternate members will be designated specific regular member(s) for whom they can substitute in the absence of the regular member(s). Must meet the requirements for the member being replaced (e.g., an alternate for the non-affiliated member must also meet the requirements to serve as a non-affiliated member).
  • Must receive all proposal materials in advance of the meeting for review if they will be voting during the meeting.
  • Alternate members are advised to "vote their conscience" as opposed to representing the position of the regular member for whom they serve.
  • If both the regular voting and alternate member both attend a meeting, only the regular voting member may vote. An alternate member may only be required to vote when necessary to achieve or maintain quorum.
  • The Director, Assistant Directors, IRB Analysts are alternate members. This enables them to be designated by the chair to review and approve minor changes to research and continuing reviews of minimal risk research.

Regular Voting Membership of the Committee on Human Research in the Medical Sciences (CHRMS)

It is recommended that CHRMS be composed minimally of 12 regular members. This may include ex officio members who have regular appointments with full voting privileges.

  • Of the total, it is recommended that 8 regular members be representatives of appropriate scientific, academic and clinical research disciplines, and which may include but are not limited to the following:
    • a pharmacist or pharmacologist
    • a psychiatrist
    • a representative of the Clinical Research Center
    • a nurse, allied health professional, or nutritionist
    • a researcher holding a Ph.D. degree in a basic biomedical science
    • a pathologist or a pathology researcher associated with the UVM/UVMMC pathology services
    • two licensed physicians from other appropriate clinical disciplines (such as pediatrics, surgery, oncology, orthopedics, neurology, obstetrics and gynecology)
    • Of the total, it is recommended that 4 regular members be non-scientific representatives. Non-scientists may include but are not limited to the following:
  • a representative of the UVMMC chaplaincy office or other appropriate member of the clergy
  • other individuals whose backgrounds and perspectives will help ensure a well- rounded and objective review board, e.g., community attorney, ethicist
  • Of the total, the membership must include at least one individual with no formal affiliation with UVM or UVMMC.

CHRMS II Membership

This Committee consists of five members, with all other CHRMS members designated as alternates.

Regular Voting Membership of the Committee on Human Research in the Behavioral Sciences (CHRBSS)

It is recommended that CHRBSS be composed minimally of 8 voting members, 2 to be nonscientific representatives, and the remainder to be representatives of appropriate scientific, academic or clinical disciplines. This may include ex officio members who have regular appointments with full voting privileges.

  • The scientific/academic/clinical representatives should include persons involved in research in the appropriate disciplines, which may include but is not limited to:
  • psychology
  • sociology/anthropology
  • education/social services
  • appropriate biomedical fields
  • other social sciences
  • Of the total, the membership must include at least one individual with no formal affiliation with UVM or UVMMC.

Consultation

The Committees may, at their discretion, obtain consultation from individuals with expertise in specialized areas to assist in the review of complex issues which require expertise beyond or in addition to that available on the IRB.

General liability insurance coverage

Actions by members carried out as a function of their Committee appointments are included under the University's general liability insurance coverage.

Monetary compensation

Appointment to the Committees is without monetary compensation.

Confidentiality

The Committees handle a large volume of material, much of which relates to yet unfunded grant proposals and contracts which are under negotiation. All materials relative to the Committees are regarded as confidential at all times, except as otherwise required by law. These materials include protocols, consent forms, minutes, agenda, and correspondence.

IRB Member Training

Before a new Committee member can be added to the roster and vote at a convened meeting, they must complete the following two items:

  • An initial orientation meeting is held with the Chair and/or Director or Assistant Director and/or Research Analysts. The initial orientation meeting includes review of human subject protection documentation including the IRB Operating Procedures, Research Manual, Reviewer Materials, the electronic submissions and reviewer software, and the RPO Website. New Committee members are educated on the IRB code of conduct, expectations for written protocol reviews, and maintaining quorum. Federal and local regulations along with institutional policy governing human subject research is also reviewed. Examples of pre-review materials and current journal articles on research may be given as additional educational material as well.
  • Completion of the Human Subjects in Research Training Module through CITI.

Before a new member can be assigned to review a protocol, they must complete their mentorship as described below. Prior experience on an IRB may substitute for some or all of the mentorship program requirements, as determined by the IRB Chair.

Member Mentorship Program

First Meeting: New member observes the meeting and may vote.

Second Meeting: New member is assigned a “Shadow” review and receives the same materials as the assigned reviewer. The new member does not need to present anything to the committee but can compare their review with the experienced reviewer’s as part of the learning process and may vote.

Third Meeting: New member is assigned a review and is paired with an experienced reviewer to do a “shadow” review. The new member should consult with the experienced reviewer, the staff or the Chair if there are any questions or concerns during the review. The experienced reviewer should be prepared to “jump in” and provide assistance if there are any concerns during the review presentation at the meeting and may vote.

Fourth Meeting: New Member does his/her own review and presentation to the Full Committee.

Documentation of Training Completion

Records of completion dates are maintained in an RPO accessible shared folder.

Continuing Education

Continuing education is accomplished by retaking the Human Subjects in Research tutorial at least once every three years, attendance at webinars, regional or national meetings and conferences. In addition, as necessary, additional education is provided in writing via Committee News and specific topics discussed during the monthly Committee meetings.

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1.3 Operations of the IRB (Sec. __.108)

Convened Meetings

The Committees meet monthly if there are agenda items.

CHRMS II is only convened when it is impracticable to convene a full meeting. This decision will be made by the IRB Research Analysts in consultation with the Committee Chair. CHRMS II will not be used to conduct regular routine business and will follow all policies, procedures and guidelines of the full committee.

Meeting Notices

Meetings are noticed on the IRB website in conformance with the Vermont Open Meetings Law (1 V.S.A. Section 310) while affording researchers with the protections of the Vermont Public Records Act Law (1 V.S.A. Section 316). The agenda, including the time and location of the meeting, are distributed in advance to all members. All pre-meeting materials for protocols are located within the electronic system.

Conducting Initial and Continuing Review

Initial and continuing convened IRB reviews and approvals will occur in compliance with 45 CFR 46, 21 CFR 50 AND 56 when applicable, and provisions of this Assurance for each project not properly found to be exempt (Section 101[b]) by the Research Protections Office. Continuing reviews, as applicable, will be preceded by IRB receipt of appropriate progress reports from the investigator, which incorporate relevant study-wide findings.

The Committees determine that all of the requirements outlined in 45 CFR 46.111 are satisfied for each protocol, including all of the requirements for obtaining informed consent and documentation of written informed consent as applicable. Reviewer forms and checklists are utilized as a guide by reviewers and other Committee members to ensure that these criteria have been met.

Continuing reviews may be approved pending requests for minor protocol edits or clarifications but are not released to the researcher until receipt of an acceptable response to the clarifications. In some instances, this process results in a continued approval date that is prior to the response date. All reviews are conducted electronically through the electronic submission and review system.

The IRB shall apply additional protections as necessary to protect potentially vulnerable research subjects. Not every human being is capable of self-determination. The capacity for self-determination matures during an individual's life, and some individuals lose this capacity wholly or in part because of illness, impaired decision-making capabilities, or circumstances that severely restrict liberty. The extent of additional protection afforded depends upon the risk of harm and the likelihood of benefit. In addition, when an IRB regularly reviews research involving a specific vulnerable population, consideration will be given to inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects. All specific IRB findings as required by 45 CFR 46 for special protections will be documented.

Written Review Procedures

The institution and the designated IRBs have established written procedures for the following, in accordance with the terms stated in the FWA. (Sec. __.108)(3)

  • verifying whether proposed activities qualify for exemption from, or waiver of, IRB review;
  • conducting IRB initial and continuing review, approving research, and reporting IRB findings to the investigator and the institution in writing as required;
  • determining which projects require review more often than annually, and which projects need verification from sources other than the investigator that no material changes have occurred;
  • ensuring that changes in approved research are reported promptly and are not initiated without IRB approval, except when necessary to eliminate apparent immediate hazards to the subject;
  • ensuring prompt reporting to the IRB, institutional officials, the relevant Department or Agency Head, any applicable regulatory body, and OHRP of any
    • (i) unanticipated problems involving risks to subjects or others in any covered research;
    • (ii) serious or continuing noncompliance with Federal, institutional, or IRB requirements; and
    • (iii) suspension or termination of IRB approval for Federally-supported research;
  • official action on protocols involving use of drugs or medical devices is taken in accordance with applicable FDA regulations governing human research review; and
  • the IRB has a process for monitoring on-going research to assess congruence with the IRB-approved protocols and compliance with applicable human subject protection guidelines and regulations, which includes monitoring a sample of studies, prioritizing the review of protocols that do not have other formal monitoring processes in place.
  • Except when certain exempt or expedited review procedure is used (as described in Sec. __.110), an IRB must review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. In order for the research to be approved, it shall

receive the approval of a majority of those members present at the meeting.

Calculation of Approval and Expiration Dates

Determination of Initial Approval Date

The IRB calculates the date of initial IRB approval in the following manner:

Protocols reviewed at a Full convened meeting:

  • When a research study is approved outright at a convened meeting, the date of the convened meeting is the date of IRB approval.
  • When the research study is approved subject to modifications at a convened meeting, the date of IRB approval is the date that the requested changes are verified by the Chair or his/her designee. For example, if the committee approves a research study subject to modifications on 10/17/17 and the response is verified by the Chair or his/her designee on 12/20/17, then the date of IRB approval is 12/20/17.

Protocols reviewed through the expedited review process:

  • When a research study is reviewed by the Chair or his/her designee and approves the project without requiring any conditions, the effective approval date is the date that the initial review was conducted.
  • When a research study is reviewed by the Chair or his/her designee and requires that the investigator make minor changes to the protocol as a condition of approval, the effective approval date will be the date that the changes are reviewed and approved by the Chair or his/her designee. For example, if the Chair or his/her designee approves a research study subject to modifications on 10/17/17 and the response is verified by the Chair or his/her designee on 12/20/17, then the date of IRB approval is 12/20/17.

Calculation of Expiration Date

The IRB calculates the date of expiration in the following manner:

Protocols reviewed at a Full convened meeting:

  • When a research study is approved outright at a convened meeting, the date of expiration is one year minus one day from the date of the convened meeting. For example, if the committee meeting date is 10/17/17, then the date of IRB expiration is 10/16/18.
  • When a research study is approved subject to modifications (which do not require further review at a subsequent convened meeting), the expiration date is one year minus one day after the date that the requested changes are approved by the Chair or his/her designee. For example, if the committee approves a research study subject to modifications on 10/17/17 and the response is verified by the Chair or his/her designee on 12/20/17, then the date of IRB approval is 12/20/17 and the expiration is 12/19/18. For logistical reasons, the IRB may set the expiration to match the date of the convened meeting just prior to the expiration date to ensure appropriate review by the full committee prior to expiration.
  • When a research study is reviewed at a convened meeting and the committee has significant concerns and requires the protocol modifications to come back to a convened meeting (i.e. tabled), the expiration date is one year minus one day of the subsequent convened meeting at which the protocol is approved, OR, if the committee approves a research study subject to modifications, the expiration date will be the date minus one day of the date that the response is verified by the Chair or his/her as indicated above for studies approved subject to modifications.

Protocols reviewed using Expedited review process:

  • When a research study is reviewed by the Chair or his/her designee and approves the project without requiring any conditions, the expiration date is one year minus one day from the date that the initial review was conducted. For example, if the initial review was conducted on 10/17/17, then the date of IRB expiration is 10/16/18.
  • When a research study is approved subject to modifications, the expiration date is one year minus one day after the date that the requested changes are approved by the Chair or his/her designee. For example, if the reviewer approves a research study subject to modifications on 10/17/17 and the response is verified by the Chair or his/her designee on 12/20/17, then the date of IRB approval is 12/20/17 and the expiration is 12/19/18.Determining date for second and all subsequent continuing reviews

Continuing reviews reviewed at a Full convened meeting

  • For all subsequent continuing reviews of a research study requiring ongoing approval, the date of the convened meeting at which the IRB conducts continuing review and approves the study (with or without conditions) is the next approval date. The expiration date will be one year minus one day after the approval date. As above, for logistical reasons, the IRB may set the expiration date less than 12 months.

Continuing reviews reviewed through expedited review process:

  • For all subsequent continuing reviews of a research study requiring ongoing approval, the date that the Chair or his/her designee conducts continuing review and approves the study (with or without conditions) is the next approval date. The expiration date will be one year minus one day after the approval date.

Voting Requirements

  1. A majority of the total number of regular voting members will constitute a quorum. The number in attendance must be one more than half the total number of regular voting members. If less than a majority of the total number of regular voting members is present, one or more alternate members may be included to constitute a quorum if they have been specifically designated to alternate for a specific absent member and meet all other membership criteria.
  2. At least one nonscientific member must be present to constitute a quorum.
  3. For review of FDA regulated articles, at least one physician must be present to constitute a quorum.
  4. Official Committee action on protocols involving human subjects will be by formal vote of a simple majority at convened meetings of a quorum of Committee members.
  5. All meetings will be conducted using Robert’s Rules of Order as guidance, with deviations made as deemed appropriate by the Chair.
  6. Official action on a protocol involving use of drugs or medical devices will be in accordance with FDA regulations governing human research review.

Withdrawal from Consideration

RPO staff will have the authority to withdraw from further Committee consideration, a study which has obtained initial approval, when the PI fails to respond to ongoing clarifications, training or continuing review submissions.

Report Findings

The Committees on Human Research, through the administrative staff, are responsible for reporting findings, actions as well as requesting clarifications to the investigators in writing, and to the appropriate offices within the institutions’ administration through reports and meeting minutes to institutional officials through their representatives on the Committee, and to sponsors of research, if so required.

Process for Appeal

There is no process delineated for appeal of Committee decisions. However, there is no prohibition for resubmission of specific requests or protocols for additional review by the Committee.

Protocols Requiring More Frequent Review

Determination of which studies require review more often than annually is done at the time of protocol review, on a case by case basis, depending upon protocol specific factors, including, but not limited to, the level of risk.

Protocols Requiring Verification from Other Sources

Determination of which studies need verification from sources other than the investigators that no material changes have occurred since previous IRB review is done on a case by case basis either by the primary reviewer at initial review, continuing review, or through information received (e.g., adverse event or unanticipated problems to subjects or others reports or complaints) and would depend upon protocol specific factors. Information is also collected through the Committee’s monitoring program and through reports from both internal sources (i.e., Protocol Review and Monitoring Committee at the Vermont Cancer Center or the Clinical Research Center’s Scientific Advisory Committee or the Research Subject Advocate) and external entities (i.e., DSMBs or sponsor monitoring visit reports).

Amendment to Protocol

The Committees on Human Research require changes in approved research to be reviewed and approved prior to initiation except where it is necessary to eliminate immediate hazard. Changes implemented to the protocol prior to Committee approval is considered noncompliance.

Unanticipated Problems/Serious or Continuing Noncompliance

The Committees on Human Research promptly report all unanticipated problems involving risks to subjects or others, serious or continuing noncompliance with applicable regulations or requirements of the IRB, and suspension or termination of IRB approval to appropriate institutional officials (the UVM Vice President for Research and the UVM Medical Center CMO when applicable) and federal agencies (i.e., OHRP, FDA and/or other agencies as appropriate). All such matters are appropriately reviewed and any necessary actions are taken to ensure continued protection of human subjects.

Determination of Significant vs Non-significant Risk Devices

For research involving investigational devices, it is the responsibility of the convened Committee on Human Research in the Medical Sciences to determine which device studies pose significant or non-significant risk when the studies do not have an Investigational Device Exemption (IDE). Studies which are determined to be significant risk must obtain an IDE from the FDA. Studies which have already obtained an IDE are assumed to be significant risk studies and this determination is not necessarily discussed or documented.

IRB Record Requirements (Sec. __.115)

The IRB keeps all records in accordance with all pertinent regulations.This record keeping includes the following.

  • Membership rosters Sec. __.108(a)(2)The institution is required to maintain a current list of IRB members identified by name; earned degrees; representative capacity; indications of experience such as board certifications or licenses sufficient to describe each member's chief anticipated contributions to IRB deliberations; and any employment or other relationship between each member and the institution, for example, full-time employee, part-time employee, member of governing panel or board, stockholder, paid or unpaid consultant. UVM rosters indicate regular voting versus alternate members, specific OHRP designation, if applicable, as well as alternate replacement assignments. Rosters are updated each time there is a change in the Committee membership. Copies of curriculum vitae are obtained and kept on file for all primary and alternate members.
  • Written procedures and guidelines including, but not limited to, the Research Manual, the FWA, and all website content.
  • Minutes of meetings indicate members and guests present, a summary of discussion on issues, a record of voting, a record of members arriving and leaving the meeting once the meeting is called to order, a record of who is alternating for whom, a record (name and number) of abstentions and “no” votes, and a report of business conducted by the expedited review process. Approved minutes will be signed by the Chair or designee, scanned, and maintained as a PDF in a shared electronic file. CHRMS II and safety meeting minutes will be uploaded along with the Agenda for the next full committee meeting for members to review online. Subsequent protocol reviews are folded back into the CHRMS system of operations.
  • Protocol files as of 2017 are electronic. Any protocol materials received prior to that are in paper format. Both the paper and the electronic files include protocols, continuing reviews, amendments, safety reports, adverse events, and consent documents. Once closed, any paper files are stored off-site and can be retrieved within 24-48 hours. Protocol files, whether paper or electronic will be destroyed after the protocol has been completed for at least six years.
  • Statements of significant new findings provided to subjects are kept in the protocol file.
  • Communications to and from the IRB are maintained in the protocol file.
  • Emergency use reports are kept in an electronic file.
  • Budget and accounting records when relevant.
  • Continuing Review (Sec. _115(a)(3) IRB will document decisions to require continuing review or full board review even in circumstances when such review is not required
  • Single IRB (Sec._115(a)(9) IRB will maintain adequate documentation of the responsibilities that each entity will undertake to ensure compliance with the cooperative research policy.

Authority to Sign IRB Documents

Implementation shall be the responsibility of the RPO Director. All Member/RPO staff signatures are electronic and in compliance with FDA 21 CFR Part 11.

a. Results of Reviews, Actions and Decisions whether Full or Expedited

Depending upon the nature of the required conditions, the IRB designates any of the following individuals or groups of individuals to determine that the conditions of approval have been satisfied:

  • The IRB chair;
  • Another member;
  • An IRB Analyst/Member or;
  • Other qualified IRB administrative staff person, who need not be an IRB member.

Individuals designated by the IRB must have appropriate expertise or qualifications. For some conditions, the review of response materials from investigators will require medical, scientific, or other technical expertise. In such cases, the IRB Chair will review the responsive materials or designate another individual who has the appropriate expertise.

Follows are some examples of conditions in which IRB Analysts/Members have been designated to review and approve response materials.

  • Correction of minor grammatical and typographical errors in the protocol or informed consent document;
  • Requiring the investigator to re-arrange sections within the consent document;
  • Requiring the investigator to change inclusion/exclusion criteria as dictated by Committee;
  • Requiring the investigator to modify proposed consent procedures dictated by Committee review;
  • Requirement to revise the protocol in a specific manner as dictated by the Committee;
  • Requiring investigator to use institutional template consent language.

b. IRB Analyst/Member Review and Approval

  • Continuing review of projects that are in data analysis, projects where work has not yet begun or Record Review Project continuing reviews;

c. Administrative Review and Approval

Protocol corrections that are only administrative in nature would not need additional IRB review because OHRP does not consider such corrections to be changes to the research. Administrative items are reviewed and approved by IRB Analysts/Members or appropriate IRB staff. IRB Analysts/Members may consult with the Committee chair prior to approval. Below are examples of administrative items.

  • Change to recruitment material
  • Correction of typographical and spelling errors in consent
  • Correction of omission of sponsor
  • IDB Updates, DSMB reports, Annual IDE Reports
  • Changes to Key Personnel
  • Not human subjects determinations
  • Not regulated activity determinations
  • Exempt determinations

d. Routine Internal Correspondence

Any action, letter, memo or e-mail between the Committee or IRB staff and the faculty or staff of the University that provides information concerning the review of research protocols by the Committee or IRB staff and which do not imply or appear to imply approval of this activity may be signed by the staff member.

e. Decisions Made by the Chair

Any letters, memos or email sent representing the decision or opinions of the Executive Chair of the IRB, other Chairs of the IRBs or their respective designees, as long as such correspondence does not imply review and approval, may be signed by IRB staff if so designated by the IRB.

Electronic Reviews

All reviews, initial, continuing and amendments are completed electronically by the IRB members as assigned. Members receive an email notice that a review is pending. Members are required to authenticate into the electronic system using their UVM NetID and password prior to completing their review. The system validates the member’s authentication credentials based upon the member’s role in the system and determines available actions for each person. The electronic review is stamped within the system with the name of the individual carrying out the review activity (electronic signature), and the time and date that the electronic signature was applied to the review.

Members only access records that they have been assigned to review.

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1.3.1 Safety Subcommittee Review of Unanticipated Problems and Compliance Issues

The IRB is required under 45 CFR part 46 to submit to the Office for Human Research Protections (OHRP) any unanticipated problems involving risk to subjects or others (UAPs). [21 CFR 56.108 (b)(1) & 45 CFR 46.103(b)(5)(i)].

Subcommittee

The Safety Subcommittee (SSC) is charged with reviewing unanticipated problems and noncompliance that involve risk to subjects or others, as well as interim additional reporting as a condition of initial approval (high risk and additional reporting categories) to determine whether any action is required and whether additional reporting to OHRP, FDA and/or local institutional officials is necessary.

The SSC is composed of a subset of Medical and Behavioral Science IRB Members, including the Executive Chair, the IRB Director, IRB Assistant Directors, research analysts, research nurses, investigational pharmacist, IRB members and Chairs from the Behavioral Sciences Committee, as necessary.

Examples of types of submissions the SSC may review are inclusive of but not limited to local adverse events, medication errors, breach of confidentiality, HIPAA deviations, protocol and consent deviations, research subject incarceration and research subject complaints.

Note Regarding Non-Local Safety Reports: For research studies subject to oversight by a Data Safety and Monitoring Board (DSMB)/Data Monitoring Committee (DMC), the IRB will rely on current reports from the DSMB/DMC in lieu of reviewing non-local safety reports. The DSMB/DMC reports should include i) what information was reviewed by the DSMB/DMC, ii) the date of review, and iii) a summary of findings and/or recommendations. It is a requirement that DSMB/DMC reports be submitted to the Committee at least annually at time of continuing review.

Definition of Unanticipated Problems (UAPs)

OHRP considers UAPs, in general, to include any incident, experience, or outcome that meets all the following criteria:

  1. unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
  2. related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized

Process for Review of Unanticipated Problems by the Safety Subcommittee

UAPs are submitted electronically by the PI to the assigned research analyst. The reviewing analyst makes an initial decision as to whether the incident being reported is an unanticipated problem using the above criteria. The analyst may make an inquiry to the researcher for additional information or they may consult with another SSC Member in the case of an adverse event for which medical expertise is necessary to make the determination. If the incident does not meet the three criteria, the report will be acknowledged and a memorandum will be sent to the PI explaining the outcome of the review and whether any further actions are necessary.

This will be documented in the Safety Subcommittee minutes and distributed to the Full Committees as applicable each month.

If the report is initially determined to meet all three criteria by either the analyst or the SSC Member, it is placed on the next available SSC agenda as New Business. If there is any doubt about the determination it will be placed on the agenda. All SSC Members will review the electronic agenda which will have embedded links to corresponding material such as; a copy of the safety submission, the last signed consent form, consent process documentation, a copy of the hospital SAFE report, physician notes or proposed corrective actions as presented by the PI.

The SSC will determine if the incident meets all three criteria as an unanticipated problem and decide what if any further actions are required to protect subjects. If further actions are required, a memorandum with the SSC’s request is forwarded to the PI. This will be documented in the subcommittee minutes. Once the requested actions are complete, the final outcome is also reported back in subsequent SSC minutes. The SSC minutes are distributed to the Full CHRMS or CHRBSS the following month.

The SSC may also make a recommendation to the full committee if it is felt that an unanticipated problem or noncompliance requires further reporting to regulators or institutional officials. Only those reports that meet the definition of unanticipated problems or serious or continuing noncompliance, which represent risks beyond that approved by the IRB, as determined by the full committee, will be reported.

This will be documented in the Safety Subcommittee minutes and distributed to the Full Committees as applicable each month. Events that are referred to the Full Committee are included in the full meeting minutes.

Range of IRB Actions for Unanticipated Problems

  1. Accept the report with no further actions;
  2. Request modifications to the protocol or the informed consent documents;
  3. Request that subjects be re-consented or notified (including past subjects) of the changes;
  4. Request further information from the Investigator or Data and Safety Monitoring Board;
  5. Refer incident to the full committee for review and recommended actions;
  6. Refer incident to other organizational entities (e.g. legal counsel, risk management, institutional officials);
  7. Request consultation from a person with specific expertise;
  8. Increase the frequency of continuing review;
  9. Impose monitoring by the IRB or an independent monitor;
  10. Report findings to regulators or others as determined by the Full Committee
  11. Suspend study enrollment and/or other study activities; or
  12. Terminate the study.

Definition of Noncompliance, Serious Noncompliance and Continuing Noncompliance

The IRBs are charged to investigate and review possible noncompliance; develop and ensure implementation of appropriate corrective actions; and ensure required reporting of any serious and/or continuing noncompliance. In all cases of noncompliance, the IRBs must assess the level of risk of harm, determine whether the research may safely continue, and specify those conditions necessary for the continued protection of human subjects.

Noncompliance is defined as the conduct of research in a manner that deviates from the approved protocol or disregards or violates federal regulations or institutional policies and procedures applicable to human subjects research. Noncompliance may result from actions or omissions by study personnel, and can range from relatively minor or technical deviations to serious deviations that threaten subjects’ rights or welfare.

Serious Noncompliance is defined as noncompliance that, in the judgement of the IRB, substantially compromises the rights and welfare of subjects; substantially impacts the integrity and validity of data; and/or compromises the integrity and effectiveness of the UVM Research Program.

Continuing Noncompliance is defined as a pattern of noncompliance (recurring or ongoing) that, in the judgement of the IRB, may indicate an underlying deficiency in knowledge of the regulations or IRB requirements or an unwillingness or inability to comply with these regulations/requirements. If unaddressed, could compromise the rights and welfare of subjects, impact the integrity and validity of the study data, and/or compromise the integrity and effectiveness of the UVM Research Program.

Process for Review of Noncompliant Issues by the Safety Subcommittee

Issues of noncompliance are submitted electronically by the PI to the assigned research analyst. The reviewing analyst makes an initial determination as to whether the issue being reported is serious or continuing using the above criteria. The analyst may make an inquiry to the researcher for additional information or they may consult with another SSC Member to assist with the determination. If the issue does not meet the criteria as serious or continuing, the report will be acknowledged and a memorandum will be sent to the PI explaining the outcome of the review and whether any further actions are necessary.

This will be documented in the Safety Subcommittee minutes and distributed to the Full Committees as applicable each month.

If the analyst has determined that the issue is serious or continuing or is uncertain, the report is forwarded to the next SSC agenda. All SSC Members will review the electronic agenda which will have embedded links to corresponding material such as; a copy of the noncompliance report, the protocol, the consent form, consent process documentation, a copy of the hospital SAFE report as applicable, and proposed corrective actions as presented by the PI. If the SSC finds that the issue does not meet the criteria as serious or continuing, the report will be acknowledged and a memorandum will be sent to the PI explaining the outcome of the review and whether any further actions are necessary.

If the SSC finds that the issue does meet the criteria as serious or continuing, the issue will either remain with the SSC for investigation and resolution or they may recommend that an

ad-hoc subcommittee be convened to conduct a formal investigation. In either case, the committees follow the Noncompliance Policy and Procedures during its review.

This will be documented in the Safety Subcommittee minutes and distributed to the Full Committees as applicable each month. Noncompliance issues that are referred to the Full Committee are included in the full meeting minutes.

IRB Actions for Noncompliance

Possible actions required by the IRB for noncompliance can be found in the Noncompliance Policy and Procedure section.

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1.3.2 Guidelines for Continuing Review of Research

Federal regulations require an IRB to conduct substantive and meaningful continuing review of human subjects research that is within the jurisdiction of the IRB. A continuing review of research begins as soon as a study is initiated. The usual real time mechanism would be a request for amendment approval, serious adverse event reports, Investigational Drug Brochure updates, etc. However, at least annually, a continuing review reminder containing a link to the IRB forms page and instructions to fill out a Request for Continuing Review form is sent to the investigator, who in turn needs to complete and electronically submit back to the IRB for review. The IRB staff will initially review the content of the report to assure that it is complete and check that the key personnel listed have completed the required training.

The criteria for continuing review are the same as those for initial review. Therefore, the IRB (or the Chair or his/her designee for protocols reviewed using expedited review procedures) must determine that all of the following requirements are satisfied:

  • Risks to subjects continue to be minimized and reasonable in relation to anticipated benefits;
  • Selection of subjects continues to be equitable;
  • Informed consent is sought or waived in accordance with 45 CFR 46.116 as well as 21 CFR 50.25 for FDA-regulated research.
  • Informed consent will be documented or documentation waived in accordance with 45 CFR 46.117 and 21 CFR 50.27 for FDA-regulated research.
  • The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects, when appropriate;
    • There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data, when appropriate; and
    • Appropriate safeguards for vulnerable subjects are provided.

Level of IRB Review

A study that requires continuing review may be reviewed at one of two levels:

Full Committee Review: Human research which does not meet the criteria for expedited review or exemption from IRB review must be reviewed by the Full Committee at a convened meeting. Continuing review of a protocol which initially required Full Committee review will continue to be reviewed by the convened Board unless:

  1. where (i) the research is permanently closed to the enrollment of new

subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or,

  1. where no subjects have been enrolled and no additional risks have been identified; or
  2. where the remaining research activities are limited to data analysis; or
  3. the protocol is a Humanitarian Use Device protocol (see FDA Guidance document issued July 8, 2010)

Expedited Review: Research which meets the criteria for expedited review is reviewed by the Chair or his/her designee. A protocol which initially was reviewed using expedited review procedures may be reviewed for continuing review using expedited review procedures. However, research protocols that previously met the criteria for expedited review will require Full Committee review if changes to the protocol are proposed which: (1) present more than minimal risk to human subjects or (2) involve procedures which do not meet the criteria for expedited review.

Assigning and completing reviews

IRB staff will electronically assign the continuing review to the reviewer based on the level of review that is required. Expedited continuing reviews are assigned and completed by one member reviewer. Continuing reviews requiring Full review will be sent to a Primary reviewer prior to the Full meeting that the continuing review is assigned to. Continuing reviews will appear on the agenda, which is sent to the IRB Committee by IRB staff prior to the meeting so that they have time to view materials. The Committee members have available to them the same information as the Primary reviewer as well as to any comments made by the Primary reviewer once their review is complete. Ballots will be provided to Committee members present at the Full meeting and votes will be cast on the ballot which is then collected by the IRB staff.

The IRB reviewer will then receive:

  1. Request for Continuing Review form completed by the PI;
  2. Last signed consent form (if applicable) and all other applicable documentation submitted by the PI
  3. Continuing Review Pre-Review Checklist as completed by the pre-reviewer (if applicable);
  4. a clean copy of the consent form (if applicable);
  5. a reviewer sheet checklist for completion

The reviewer will have available to them the full protocol and all submissions and correspondences pertaining to the protocol electronically.

Important issues for primary reviewers are:

1. That the risks to subjects are still minimized.

    1. by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
    2. whenever appropriate by using procedures already being performed on the subjects for diagnostic or treatment purposes.
  1. That the risks to subjects are still reasonable in relation to anticipated benefits.
  2. That the number of subjects initially requested and approved has not been exceeded.
  3. Any protocol revisions that have been approved by the IRB since the last continuing review.
  4. Any request for protocol revision at the time of continuing review have been submitted.
  5. Determine if the study appears to be progressing as planned.
  6. If unexpected events, toxicity, or complications have occurred that may indicate a need for a change in the protocol or consent.
  7. If the subjects registered any complaints about the study.
  8. Whether the consent document that is currently in use contains all previous revisions.
  9. Review a current data safety and monitoring report to determine that the data and study events are being evaluated on a regular basis. It is appropriate for the IRB to require a protocol revision to improve the plans for data and safety monitoring if the IRB thinks this will improve the protection of research subjects.

Reviewer Responsibilities

  • Review as above.
  • Talk directly with PI to attempt to clarify/resolve major concerns prior to approval.
  • Identify any remaining issues, which may need to be discussed further with the full Committee.
  • Reviews are assigned electronically and should be completed electronically using the Electronic Continuing Review Instructions located on the Committee Login page.

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1.3.3 Guidelines for Review of Amendments

The IRB is responsible for review of any changes to previously approved research prior to implementation. These changes are often referred to as “amendments” or “protocol revisions.”

Major amendments that potentially affect the risk/benefit ratio must be reviewed through the full committee review process, minor modifications not affecting the risk to subjects may be reviewed through the expedited review process.

When amendments impact the safety of subjects previously enrolled who continue to receive study interventions, it may be necessary to convey this information (e.g., to obtain the consent of the subjects) by means of an addendum to the existing consent form, use of a new form, or providing the subjects with an informational sheet regarding the update. The IRB may determine, for example, that such subjects must be notified of new findings or toxicities not noted at the time they were originally consented. Such notification is consistent with the view of informed consent as a continuous process, and affords subjects the opportunity to determine whether or not they wish to continue their participation in the research. The IRB shall determine on a case-by-case basis when such notification, and its documentation, is required.

The criteria for reviewing an amendment are the same as those listed for initial review. However, in most cases the review of the amendment can be more focused. Our form, the “Request for Modification/Amendment to Approved Protocol” was designed to assist in this review.

1. What part of the research study is being revised? This identifies specifically what we are being asked to review, e.g., inclusion/exclusion criteria, scientific changes, consent.

2. Does the revision affect the risk to subjects? If so, the following issues should be addressed: are the risks still reasonable in relation to the anticipated benefits and the importance of knowledge that may reasonably be expected to result? Does the protocol still meet the criteria that are used to evaluate new studies?

3. Does the currently approved consent form require revisions to convey the potential risks? The amendment should be accurately reflected in the consent form, if appropriate. Should currently enrolled subjects be informed or re-consented?

When an amendment requires full review:

Member Reviewer should:

  • Review the amendment to determine that the above requirements under #2 and #3 are satisfied.
  • Talk directly with PI to attempt to clarify/resolve major concerns prior to the meeting.
  • Identify any remaining issues which need to be discussed.
  • Ensure that the Lay Summary/Consent Form accurately and appropriately reflects the protocol and would be understandable to an average person.
  • Outline any problems or issues that deal with the protocol or Consent Form. Editorial recommendations and indications of jargon can be corrected on your copy, submitted to staff and noted in the presentation that "editorial changes are suggested on my copy."

When amendment requires expedited review:

Chair or designee should:

  • Review as above.

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1.4 Public Records and Open Meetings (Vermont Law)

Federal Freedom of Information Act (FOIA)

The Freedom of Information Act (FOIA) is a federal law that generally provides that any person has a right, enforceable in court, to obtain access to federal agency records. All federal agencies, including EPA, are required to make requested records available unless the records are protected from disclosure by one of nine FOIA exemptions contained in the statute.

The FOIA applies only to federal agencies. It does not apply to records held by Congress, the courts, or by state or local government agencies. Each state has its own public access laws that should be consulted for access to state and local records.

Vermont Public Records Act

State open records laws are state statutes that govern access to records in the possession of state and local governments and other state public bodies, such as public universities.

The University of Vermont is a public body subject to the Vermont Public Records Act (1 V.S.A. §316)(a). Under this statute, any person may inspect or copy any public record of a public agency. The definitions of public agency; public records and documents are included in 1 V.S.A. §317.

Vermont State Exemptions to FOIA

Vermont statute exempts research data and protocols under §317(c)(23). Because these records are exempt from public disclosure, the FOIA cannot be employed to inspect or copy records. Researchers should forward any request for inspection or copies of research records to the Vice President for Executive Operations according to the UVM Records and Document Request policy.

Vermont Open Meetings Law

The University of Vermont is a public body subject to the Vermont Open Meetings law §312. All meetings of a public body are declared to be open to the public at all times, except as provided in §313 Executive Sessions.

Executive Session Exemption under the Vermont Open Meeting Law

“A public body may not hold an executive session except to consider one or more of the following:”

“(a)(6) records exempt from the access to public records provision of §316 of this title; provided, however, that discussion of the exempt record shall not itself permit an extension of the executive session to the general subject to which the record pertains;”

The Committees’ convened meetings are open and move into executive session only after an affirmative vote of two-thirds of its present members. Such vote is taken in the course of an open meeting and the result of the vote recorded in the minutes. A motion to go into executive session must indicate the nature of the business of the executive session, and no other matter may be considered in the executive session. No formal or binding action will be taken in executive session.

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Section II Research Guidance

 

2. Coordination with Other Compliance Committees/Divisions

The Committees on Human Research Office is not the only entity responsible for oversight of human subject research.  The Office for Clinical Trials Research (OCTR), the The University of Vermont Cancer Center (UVMCC) and the Clinical Research Center (CRC) are entities across UVM and UVM Medical Center that play a role in protecting human subjects in research including information collected about subjects.   Unique requirements may be in place if your research activity is performed with the support of one of these units.  If so, you should contact the administrative staff for the appropriate unit to determine what, if any, additional responsibilities may be active during the conduct of your research.  In addition, these entities share the protocol status, correspondence related to the protocol, adverse events, and monitoring information.  This sharing avoids duplication of efforts and also affords a higher level of protection for the subjects.

The University of Vermont Cancer Center Protocol Review and Management Committee (PRMC)

Any initial review or change to protocols regarding the study of cancer, require prior review by the PRC. Review by the PRC is independent of the review by the Institutional Review Board (IRB). PRC and IRB, however do share their Committee review correspondence and outcomes with each other. While submissions may be made to both Committees at the same time, the PRC must approve the protocol or approve with clarifications (that do not require a subsesquent full committee review) prior to the IRB review. This is to make certain the PRC clarifications and responses can be taken into consideration during the IRB review. This is required for all initial submissions and amendments.

Scientific Advisory Committee (SAC)

Any protocols wishing to utilize resources of the Clinical Research Center require review by the SAC. Review by the SAC is independent of the review by the Institutional Review Board (IRB). However, the findings from the IRB review are communicated to the SAC. Submissions may be made to both Committees at the same time, however SAC will not approve until the IRB has approved the project.

Office of Biotechnology Activities/Recombinant DNA Advisory Committee

Novel Human Gene Therapy experiments are required to undergo extensive review and final approval through the Office of Biotechnology Activities/Recombinant DNA Advisory Committee (OBA/RAC) which is a government entity. The IRB requires documentation of the OBA/RAC approval prior to IRB protocol review.

Institutional Biosafety Committee (IBC)

Any protocols that involve the use of gene therapy require review by the IBC. Approval to begin activities will not be released until IBC approval is obtained. Submissions may be made to both Committees simultaneously but human subject activities must not begin until both Committees have approved the protocol.

Radiation Safety Office (RSO)

The RSO at UVM oversees the use of ionizing radiation sources on campus and ensures compliance with state and federal regulations, to protect UVM employees, students, the public, and the environment. The RSO also provides safety related services for UVM. Any protocols involving the application of radioactive materials, radioisotopes, and/or radiation treatment to humans for nonclinical purposes must undergo review by the UVM Radiation Safety Office if the research procedures are taking place at UVM. If the research procedures are taking place in UVM Medical Center, you should contact the UVM Medical Center Radiation Safety Committee.

Sponsored Project Administration (SPA)

SPA requires documentation of protocol approvals prior to release of funds for sponsored projects.  IRB staff share protocol statuses with SPA for this purpose.

Office for Clinical Trials Research (OCTR)

OCTR assists with the majority of the industry- funded protocols by developing contracts, invoicing and collecting IRB fees for the investigators. Protocol information is shared for these purposes.

UVM Medical Center Compliance Office

The 2010 Affiliation Agreement between the University of Vermont (UVM) and UVM Medical Center requires approval of a billing plan by UVM Medical Center Compliance for all protocols utilizing UVM Medical Center resources regardless of whether they are UVM or UVM Medical Center studies. The IRB assists UVM Medical Center Compliance in identifying protocols that require a billing plan and will release final protocol approvals to UVM Medical Center Compliance if the billing plan is the only outstanding item.

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3.0 IRB Review Categories (Sec._46.109(a))

An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities, including exempt research activities. These review categories are employed for new protocols, continuing reviews, and amendments to existing protocols.

3.1 Full Committee Review

The IRBs employ the convened meeting review process for review and approval of studies that are more than minimal risk.

Notification to Research Community

Committee meetings are noticed on the Committee website. Deadline for submission of new protocols is 4 weeks in advance. This time allows for the appropriate pre-review procedures as described below.

Notification to the Committee

Distribution of the Agenda to all members occurs approximately 2 weeks in advance of the convened meeting. Approximately 5 days prior a convened meeting a second distribution of any additional continuing full protocols received after the deadline is sent to all members. All new protocols, amendments, continuing reviews and other business requiring full committee action are placed on the Agenda for discussion.

Access to the Protocol Materials

Committee members have access to all of the protocol materials through the electronic submission and review system.

Pre-review Procedures

Similar to granting agency review, IRBs must receive sufficient information from investigators to provide adequate review of proposed research and to make the determinations required by regulations for IRB approval.

Inclusion on a Committee agenda is not guaranteed, until your department-assigned IRB analyst completes a pre-review of the submission. A specific checklist is followed to determine if the submission is ready for full committee review. If the submission is incomplete or lacks information necessary to conduct a full committee review, it will be withdrawn from the current agenda. The PI will be notified along with a list of requirements for resubmission. It will be placed on an agenda when the submission is found to be satisfactory.

Reviewer Assignments

A Primary and Secondary Reviewer is assigned to review the complete protocol, consent form, Investigational Drug/Device Brochure and any other protocol materials. This includes any pre-review checklists completed by the IRB analyst. Efforts are made to match the primary reviewer’s expertise to the protocol subject matter. Reviewers are encouraged to contact the PI to resolve/clarify major concerns prior to the meeting. The reviewers summarize the protocol or amendment for the full Committee at a convened meeting and answer questions during the discussion. The member reviewer(s) will determine that the following requirements are satisfied prior to approval:

Requirements for Approval

  1. Risks to subjects are minimized:
    1. by using procedures which are consistent with sound research design;
    2. do not unnecessarily expose subjects to risk, and
    3. whenever appropriate by using procedures already being performed on the subjects for diagnostic or treatment purposes.
  2. Risks to subjects are reasonable in relation to anticipated benefits to subjects, and the importance of knowledge that may reasonably be expected to result. In evaluating risks and benefits only those risks and benefits that may result from the research should be considered (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).
  3. Selection of subjects is equitable. The purposes of the research, the setting in which the research will be conducted, and the population from which subjects will be recruited should be taken into account.
  4. Absent the IRB granting a waiver of consent or waiver of documentation of consent, informed consent will be sought from each prospective subject or the subject’s legally authorized representative and will be documented in accordance with applicable regulations. (45 CFR 46.116&46.117) Consent document will be reviewed to ensure it accurately reflects the protocol and would be understandable to a reasonable person.
  5. Where appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of subjects.
  6. Where appropriate, the research plan makes adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
  7. Where some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, persons who lack capacity to consent, or economically or educationally disadvantaged persons, appropriate safeguards are included in the study to protect the rights and welfare of these subjects. (Subparts B, C, D)

Documentation

The IRB minutes will include documentation of the discussion of the studies that were reviewed at the convened meeting as well as the votes and any abstentions and determinations of applicability of any subparts. The continuing review votes are accomplished by paper ballot in the meeting and entered into the electronic system post meeting.

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3.2 Expedited Review (Sec._46.110)

The IRBs employ the expedited review process for approval of studies that are determined to be minimal risk and only involves activities on the Secretary’s list (OHRP, FDA or other Federal Agency, as indicated in Code of Federal Regulations, ( 45 CFR 46.110 and 21 CFR 56.110).

To see a list of expedited categories, OHRP Expedited Review Categories (1998).

The expedited review process is also employed for approval of

  • study modifications involving no more than minimal risk,
  • when conducting limited IRB review as required by the exemptions at Sec. _.104(d)(2)(iii), Sec. _.104(d)(3)(i)(C), Sec. _.104(d)(7), and Sec. _.104(d)(8)., (pre-2018 Common Rule- disregard)
  • and also when the IRB reviews and approves research with conditions at a convened meeting without requiring further review at a subsequent convened meeting.

Note: The IRB is required to document rationale when they override the presumption that studies on the Secretary’s expedited review list involve greater than minimal risk (Sec. _.115(a)(8)). (pre-2018 Common Rule- disregard)

Pre-review Procedures

IRBs must receive sufficient information from investigators to provide adequate review of proposed research and to make the determinations required by regulations for IRB approval. Submission requirements can be found on our website and the IRB analyst can be contacted with any questions.

Review by a member is not guaranteed, until your department-assigned IRB analyst completes a pre-review of the submission. A specific checklist is followed to determine if the submission is ready for member review. If the submission is incomplete or lacks information necessary to conduct a member review, the PI will be notified along with a list of requirements for resubmission. The protocol will be sent for review when the submission is found to be satisfactory.

Reviewer Assignment

One Committee member is assigned to review the complete protocol or amendment, consent form, Investigational Drug/Device Brochure and any other applicable protocol materials. This includes any pre-review checklists completed by the IRB analyst.

The designated IRB member reviewer will conduct the review and document his/her determination of the applicable expedited review category. Consistent with review by a convened IRB, expedited member reviewer will consider the Requirements for Approval as listed above.

Expedited member reviewers, as designated by the IRB, may exercise all of the authorities of the IRB, except that he/she may not disapprove the research. A research proposal may be disapproved only after review by the convened meeting.

Notification to the Board

When the expedited review procedure is used, all regular members will be informed of expedited actions via the IRB Agenda generated for the next convened meeting.

Documentation

The IRB Minutes will include documentation of the studies that were reviewed under an expedited review process.

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3.3 Limited Review (Sec._46.104) (New section! Do not reference until the 2018 revised Common Rule takes effect)

Limited IRB review is making and documenting the determination required by 46.111(a)(7), to ensure that there are adequate privacy safeguards for identifiable private information and identifiable biospecimens in the proposed research.

There are new categories of exemptions that require limited review by an IRB member. To avoid confusion with addition of this new review type, the UVM IRB will always review any exempt categories that require a member review under the expedited review process see section 3.3. IRB analysts are IRB members and have the authority delegated to conduct these determinations.

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3.4 Exemption Determination

The Department of Health and Human Services has identified categories of research qualifying for exemption from certain federal regulations applicable to research involving human subjects. The IRB makes federal exemption determinations according to 45 CFR 46.101.

Protocols fitting the exempt criteria will be reviewed and determined exempt by qualified IRB personnel in coordination with the Chair as necessary.

According to federal regulations, Committee review is not required for certain categories of research activities that involve little or no risk to human subjects. However, the University and UVM Medical Center have an obligation to be apprised of all human subjects’ research being conducted under their auspices in the event any questions or problems arise and in order to assure that, regardless of risk, all research subjects are afforded the same protection.

Research involving surveys or interview procedures in children is not exempt from a Committee review. HHS believes that children being surveyed or interviewed by an investigator may not be capable of recognizing that their responses to questions on sensitive issues could be potentially damaging to themselves or others. For this reason, the IRB is required to at least review such research to determine whether the rights and welfare of the children participating as subjects are adequately protected.

In most exempt projects the participant’s signature on a consent form is not necessary. Consent may be obtained verbally or may be implied by the completion of the research requirement. It is suggested that an Information Sheet be developed for the potential participant’s reference. If you are planning on using an Information Sheet, the Committee must review it.

Research which is determined to be exempt from Committee review must comply with all University of Vermont policies and procedures, as well as with applicable federal, state and local laws regarding the protection of human subjects in research.

Note, that any revisions to the research affecting human subjects may affect the original determination of exemption and therefore must be prospectively submitted for review and subsequent determination of exemption.

Research activities in which the only involvement of human subjects will be in one or more of the categories listed below may be considered "exempt". Please note, however, that although the research is exempt from formal review, it is not necessarily exempt from informed consent requirements.

The Department of Health and Human Services has identified categories of research qualifying for exemption from certain federal regulations applicable to research involving human subjects. The IRB makes federal exemption determinations according to 45 CFR 46.101.

One additional non-federal exemption category may be applied to non-federally supported or otherwise non-federally regulated studies. Exemption category #7 is based upon commonly accepted, minimal risk research practice originally defined in 45 CRF 46.110 receiving expedited IRB review procedure.

Exemption #1: Normal Educational Practices and Settings

Research conducted in established, or commonly accepted educational settings, involving normal educational practices, such as

(i) research on regular and special education instructional strategies, or

(ii) research on the effectiveness of, or the comparison among, instructional techniques, curricula, or classroom management methods.

Exemption #2*: Educational Tests, Surveys, Interviews, or Observations

Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observations of public behavior*, unless:

(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and

(ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability, or be damaging to the subjects' financial standing, employability, or reputation, or deals with sensitive aspects of the subject's own behavior, such as illegal conduct, drug abuse, sexual behavior or the use of alcohol.

*Note: The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or observation of public behavior, does not apply to research with children, subpart D, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.

Exemption #3: Identifiable Subjects in Special Circumstances

Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observations of public behavior that is not exempt under exemption #2, if:

(i) the human subjects are elected or appointed public officials or candidates for public office; or

(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

Exemption #4: Collection or Study of Existing Data

Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that the subjects cannot be identified, directly or through identifiers linked to the subjects. Note: This may not constitute “human subjects research” if the investigators/collaborators will not have access to the identities of the subjects. See the section in this manual titled Guidance on Research Involving Coded Private Information or Biological Specimens

Exemption #5: Public Benefit or Service Programs

Research and demonstration projects which are conducted by or subject to the approval of the [Federal] Department or Agency heads, and which are designed to study, evaluate, or otherwise examine: (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs.

Exemption #6: Taste and Food Evaluation and Acceptance Studies

Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food and Safety and Inspection Service of the U.S. Department of Agriculture.

Non-Federal Exemption #7: Research involving collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, where this information is personally identifiable or coded. Note: Prisoner research, research that is federally funded, and data that includes Protected Health Information (PHI) do not meet the criteria for this exemption.

Documentation

The IRB Minutes will include documentation of the studies that were reviewed under an exempt review process.

Exemption Determinations (Sec.__.104) (New section! Do not reference until the 2018 revised Common Rule takes effect)

Committee review is not required for certain categories of research activities that involve little or no risk to human subjects. However, the University and UVM Medical Center have an obligation to be apprised of all human subjects’ research being conducted under their auspices in the event any questions or problems arise and to assure that, regardless of risk, all research subjects are afforded the same protection. Therefore, the UVM IRB will make all exempt determinations for UVM/UVMMC research projects.

Research which is determined to be exempt from Committee review, must comply with all University of Vermont policies and procedures, as well as with applicable federal, state and local laws regarding the protection of human subjects in research. Please note, however, that although the research is exempt from formal review, it is not necessarily exempt from informed consent requirements.

Authority to Grant Exempt Status

Prior to the 2018 Common Rule change, all exempt determinations were delegated to experienced IRB staff. The rule has modified some of the categories to now allow recording of identifiable information. Determinations in these modified categories will require an IRB member conduct the determination. IRB analysts are IRB members and will be making these determinations.

Length of Determinations

Once a project has been determined to meet the criteria for exemption, there is no expiration date for the project and ongoing IRB oversight is not required.

Changes to the Project/Amendments

Any proposed changes to the project may affect the original determination of exemption. Therefore, revisions must be prospectively submitted for review and subsequent determination of exemption.

Exemption Categories

The exempt categories have been revised and expanded under the 2018 Common Rule change.

#1 – EDUCATIONAL EXEMPTION

What's New:  A new ineligibility criterion will be added to this interaction/intervention exemption for research that involves possible "adverse effects" on student learning of the required education content and/or on the assessment of educators.

(1) Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students' opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

#2 - SURVEYS, INTERVIEWS, EDUCATIONAL TESTS, AND OBSERVATION OF PUBLIC BEHAVIOR

What's New: The scope will be expanded to include the collection of sensitive and identifiable data.  However, the following is not allowed:

  • Interventions
  • The collection of biospecimens
  • Research with children (except for educational tests or some public observation)

(2) Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:

(i) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;

(ii) Any disclosure of the human subjects' responses outside te research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or

(iii) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by § __.111(a)(7).

# 3 - BENIGN BEHAVIORAL INTERVENTION (NEW)

The 2018 Common Rule added this new exemption category because respect for persons is accomplished through the prospective subject’s forthcoming agreement to participate, the research activities pose little risk, and the use of this exemption for many social and behavioral studies will enable IRBs to devote more time and attention to studies involving greater risk or ethical challenges.

What's New:  This new exemption permits data collection via an interaction (e.g., survey, interview, audio/visual recording) from adult subjects with prospective agreement.  However, the following is not allowed:

  • Research with children
  • Deception, unless prior agreement obtained
  • Physiological data collection methods (e.g., EEG; wearable devices, such as FitBitTM; blood pressure monitors)
  • Linking to additional personally-identifiable data

(3)(i) Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:

(A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;

(B) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or

(C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by § __.111(a)(7).

(ii) For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. Provided all such criteria are met, examples of such benign behavioral interventions would include having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.

(iii) If the research involves deceiving the subjects regarding the nature or purposes of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware of or misled regarding the nature or purposes of the research.

#4 - SECONDARY RESEARCH (IDENTIFIABLE PRIVATE INFORMATION/BIOSPECIMENS) 

Secondary research is referring to the re-using identifiable information and identifiable biospecimens that are collected for some other “primary” or “initial” activity. The information or biospecimens that are covered by this exemption would generally be found by the investigator in some type of records (in the case of information) or some type of tissue repository (such as a hospital’s department for storing clinical pathology specimens).

The goal of this exemption is to facilitate secondary research using identifiable private information or identifiable biospecimens that have beenor will be collected or generated for nonresearch purposes or from research studies other than the proposed research study.

What's New: The scope of this exemption will be expanded to allow:

  • Prospective data review
  • Maintenance of identifiers, if all study data is protected health information (PHI)
  • Research that is conducted by, or on behalf of, a Federal department/agency or using government-generated or government-collected information obtained for non-research activities

(4) Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met:

(i) The identifiable private information or identifiable biospecimens are publicly available;

(ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;

(iii) The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E (HIPAA), for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or

(iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for nonresearch activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.

#5 - PUBLIC BENEFIT/SERVICE PROGRAM RESEARCH (FEDERAL DEMONSTRATION PROJECTS)

What's New:  A new eligibility criterion for this interaction/intervention exemption will be that the project must be published on a federal website.

(5) Research and demonstration projects that are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads (or the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. Such projects include, but are not limited to, internal studies by Federal employees, and studies under contracts or consulting arrangements, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities such as sections 1115 and 1115A of the Social Security Act, as amended.

(i) Each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible Federal Web site or in such other manner as the department or agency head may determine, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision. The research or demonstration project must be published on this list prior to commencing the research involving human subjects.

#6 - TASTE/FOOD QUALITY EVALUATION & CONSUMER ACCEPTANCE

What's New:  Unchanged

(6) Taste and food quality evaluation and consumer acceptance studies:

(i) If wholesome foods without additives are consumed, or

(ii) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

#7 - STORAGE / MAINTENANCE OF IDENTIFIABLE DATA/BIOSPECIMENS OBTAINED WITH "BROAD CONSENT" (NEW)

What's New:  This new exemption allows for the storage of data and/or biospecimens in a repository, with identifiers maintained, that were collected under an approved IRB protocol with "Broad Consent" for future secondary use research.  

UVM will not implement Exemption #7 at this time

#8 - USE OF IDENTIFIABLE DATA/BIOSPECIMENS OBTAINED WITH "BROAD CONSENT" (NEW)

What's New:  This new exemption allows for secondary research use/analysis of identifiable data/biospecimens that were collected under an approved IRB protocol with "Broad Consent".

UVM will not implement Exemption #8 at this time

#9 – University of Vermont Non-Federal Exemption Research involving collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, where this information is personally identifiable or coded.

What's New:  This category has been retired.

Can Research Regulated by the Subparts Be Exempt?

Subpart B, Additional Protections for Human Fetuses and Neonates Involved in Research

The final rule section__.104(b)(1) states that all of the exemptions at Sec. __.104 may be applied to research conducted under subpart B, if the conditions of the exemption are met.

Subpart C, Additional Protections Pertaining to Biomedical & Behavioral Research Involving Prisoners as Subjects

Language at Sec. __.104(b)(2) states that none of the Sec. __.104 exemptions may be applied to research conducted under subpart C except for research aimed at involving a broader subject population that only incidentally includes prisoners.

Subpart D, Additional Protections for Children Involved as Subjects in Research

The language at Sec. __.104(b)(3) relevant to subpart D, states that some of the exemptions may be applied.

  • Categories 1, 4, 5, and 6

Sec. __.104 (d)(1), and (d)(4)-(8) of this section may be applied to research that is subject to subpart D if the conditions of the exemption are met.

  • Category 2

Sec. __.104(d)(2)(i) and (ii) of this section may apply only to research activities that are subject to subpart D involving educational tests or the observation of public behavior when the investigator(s) do not participate in the activities being observed.

  • Category 2

Sec.__.104(d)(2)(iii) of this section may not be applied to research that is subject to subpart D, because protections, including IRB review and parental permission, are appropriate for research involving children and educational tests, surveys or interview procedures, or observation of public behavior when the information collected may be individually identified and sensitive in nature.

Notification

Exemption determination documentation is forwarded to the principal investigator indicating the exemption category.

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3.5 Not Human Subjects Research Determination

The IRBs employ the determination of Not Human Subjects for research activities that involve only the use of data and/or specimens that have no directly identifiable information and were obtained without intervention or interaction with the individual. The determination of research not involving human subjects can only be made by the IRB.

Qualified IRB analysts, in consultation with the IRB leadership as necessary, will make these determinations.

Not human subjects does not apply to deceased individual data. The IRB does not need to make these determinations, however you do need to work with the hospital to allow for the use of the decedent’s protected health information. The required hospital form is on our form webpage.

Documentation

The IRB Minutes will include documentation of the studies that were determined not to include human subjects.

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3.6 Not Research Determination

Determining whether a project constitutes human subjects research rather than quality improvement or program evaluation involves multiple factors. The federal definition of research is “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge." In contrast, quality improvement projects or program evaluation projects systematically collect data for administrative, clinical, or reporting purposes, but are not designed to contribute to, or to advance generalizable knowledge. Instead, they are designed to develop or contribute to knowledge relevant to the organization. See the table below for a summary of the differences.

The IRB Office has often requested to provide a determination on whether a project is research under the Federal regulations or is rather program evaluation or quality improvement. Formal IRB determinations are requested in anticipation of such documentation being required for journals, conferences, funding sources and others. The IRB has developed a not research self-determination tool which guides as to whether the project is quality improvement versus research requiring IRB review. Documentation can be printed at the completion of the checklist. Please note that this is not an ethical review of the project as that responsibility falls to the individual or institution that is conducting the quality improvement project.

Proceed to the Self-Determination Tool


Overview of Differences Between Research Under Regulations and Quality Improvement or Program Evaluation
  Research Quality Improvement Program Evaluation

Intent/Purpose

Intent of project is to develop or contribute to generalizable knowledge (e.g., testing hypotheses) Intent of project is to improve a practice or process within a particular institution or ensure it confirms with expected norms Intent of project is to improve or assess a specific program

Deviation from Standard Practice

May involve significant deviation from standard practice Unlikely to involve significant deviation from standard practice  

Design

May involve randomization of individuals to different treatments, regimens or educational practices Generally does not involve randomization to different treatments, or practices Does not involve randomization of individuals, but may involve comparison of variations in programs

Effect on Program or Practice Evaluated

Findings of the study are not expected to directly affect institutional or programmatic practice Findings of the study are expected to directly affect institutional practice and identify corrective action(s) needed Findings of the evaluation are expected to directly affect the conduct of the program and identify improvements

Population

Usually involves a sample of the target population- universal participation of an entire clinic, program, or department is not expected; statistical justification for sample size is used to ensure endpoints can be met Information is collected on all or most of the target population Information on all or most participants in the program

Risks/Burdens

May put participants at risk Does not increase risk to participants, with exception of possible privacy or confidentiality concerns No risks to participants expected

Dissemination of Results

Intent to publish or present generally presumed If the results are publicized, they are described as “quality improvement” in public presentations, academic curriculum vitae, publications, etc.

Intent to disseminate the information to program stakeholders and participants is assumed

This may be publicly posted (e.g., website) to ensure transparency of results

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3.7 Determination of Institutional Engagement in Research

Researchers are not always clear as to whether they or their colleagues are engaged in the research project depending on the roles and responsibilities they have. If UVM is found to be engaged in research, then our IRB must review and approve the project. See guidance below.

Review Process

Investigators may make this determination themselves, however, the IRB can acknowledge the determination.

Documentation

Any documentation generated from an acknowledgement of engagement in research is kept in a shared IRB file.

Guidance

An institution is considered engaged in human research when employees or agents for the purposes of the nonexempt research project, obtains: (1) information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (2) obtains, uses, studies, analyzes or generates identifiable private information or identifiable biospecimens; or (3) obtains the informed consent of human subjects for the research. An institution is also considered engaged when the institution receives a direct federal award to conduct human subject research, even when all activities involving human subjects are carried out by a subcontractor.

It is not a requirement that this determination be made by the IRB, however we can review and acknowledge your determination upon request.

Category

Description of UVM Activities

UVM Engaged?

Other Site Engaged?

Funding Only/No Direct UVM Involvement

UVM receives a direct grant or award to perform human subjects research, even if all of the activities are performed off-site by subcontractors or collaborators and UVM itself never intervenes or interacts directly with human subjects and never receives identifiable private information.

YES

YES

Pre-Research Activities

UVM performs a feasibility study to determine whether sufficient data or prospective participants exist to formulate a hypothesis or conduct a study.

MAYBE

n/a

UVM performs a small pilot study to work out details of an anticipated future research project.

YES

UVM intervenes or interacts with individuals who meet study eligibility criteria to develop study protocol.

YES

PR/Publicity/Pre-Screening Activities

UVM informs potentially eligible subjects about research occurring elsewhere and provides them with information about how to contact the researchers.

NO

YES

UVM sends letters to prospective subjects describing a study and letting them know they may later be contacted to participate.

YES

MAYBE

Study Recruitment/Informed Consent

UVM informs prospective subjects about the availability of research conducted elsewhere; provides prospective subjects with written information about research (including the relevant informed consent document and other IRB-approved materials); provides prospective subjects with information about contacting investigators for information or enrollment; or obtains and appropriately documents prospective subjects' permission for investigators to contact them. Generally, a UVM clinician may discuss the study with the prospective subject as the subject's clinician but not as a researcher or part of the study team. *Documentation of permission must be HIPAA-compliant if the UVM investigator is affiliated with a unit covered by HIPAA.

NO

YES

UVM faculty, staff, trainees, or agents conduct the consent interview, obtain subject signature on the consent form, or otherwise act as authoritative representatives of the investigators.

YES

YES

UVM researchers obtain permission from a school or nursing home to observe, audio/videotape, or distribute surveys/questionnaires for research purposes. The students or residents are consented by the UVM researchers to participate in the project.

YES

NO

Data/Specimen Repositories

UVM data steward queries UVM database on behalf of external researchers.

NO

YES

UVM releases information and/or specimens to investigators at other site in non-identifiable (i.e., non-linkable) form, when the information and/or specimens were originally obtained for non-research purposes.

NO (Not Human Subjects)

NO

UVM receives information or specimens for research from established repositories operating in accord with an FWA, OHRP guidance on repositories, and a written agreement unequivocally prohibiting release of identifying information to UVM investigators.

NO (Not Human Subjects)

YES

UVM obtains, receives, or possesses identifiable (directly or with links/codes) private information from another site for research purposes.

YES

YES

Multi-Site Research UVM is Statistical/ Data Coordinating Center

UVM obtains, receives, or possesses identifiable (directly or through links) private information to operate a ‘statistical or data’ coordinating center for multi-site collaborative research. If the UVM investigator is within the covered entity, i.e. affiliated with a unit covered by HIPAA they are required to obtain the appropriate documentation of HIPAA compliance from the site(s) submitting identifiable private information. If UVM has no other interaction or intervention with subjects, and the principal risk associated with institutional activities is limited to the potential harm resulting from breach of confidentiality, then the UVM IRB need not review each underlying collaborative protocol. However, the IRB should determine and document that: (i) the statistical/data coordinating center has sufficient mechanisms in place to ensure the privacy of subjects and confidentiality of data are adequately maintained; (ii) each collaborating institution holds an FWA or other appropriate assurance; (iii) each protocol is reviewed and approved by the IRB at the collaborating institution prior to enrollment of subjects; and (iv) informed consent is obtained from each subject in compliance with HHS regulations, the Common Rule, and any other applicable federal policy.

YES

YES

Multi-Site Research UVM is the Lead or Operations Coordinating Center

UVM obtains, receives, or possesses identifiable (directly or through links) private information to operate a "lead or operations coordinating center" for multi-site collaborative research. If UVM as the lead/operations coordinating center has no other interaction or intervention with subjects, the UVM IRB need not review each underlying collaborative protocol. However, the IRB should determine (i) management, data analysis, and Data Safety and Monitoring (DSM) systems are adequate, given the nature of the research involved; (ii) sample protocols and informed consents are developed and distributed to each collaborating institution; and (iii) each collaborating institution holds an applicable OHRP-approved Federalwide Assurance (FWA); (iv) each protocol is reviewed and approved by the IRB at the collaborating institution prior to enrollment of subjects; and (v) any substantive modification by the collaborating institutions of sample informed consent information related to risks or alternative procedures is appropriately justified; and (vi) informed consent is obtained from each subject in compliance with HHS regulations, the Common Rule, and any other applicable federal policy.

YES

YES

Medical Care/ Standard Clinical Practice

UVM provides unforeseeable but medically appropriate clinical treatment incident to a patient's participation in a clinical trial elsewhere, e.g., when patient suffers an adverse event that is treated at UVM by her regular health care provider.

NO

YES

Patient is hospitalized at UVM and attending physician decides continued participation on protocol at outside institution is ok.

NO

YES

Medical Care/
Little or No Direct UVM Involvement/
Data Not Collected for Study

UVM administers test article and performs normal monitoring, but does not perform data collection.

NO

YES

UVM performs blood draw for a genetics study occurring at another institution but sends the samples to the other institution for analysis.

NO

YES

UVM provides pre- and/or post-test genetic counseling to study participants regarding tests conducted by and results reported from other institution.

NO

YES

Subinvestigators

UVM consents prospective subjects (even if for "someone else's study").

YES

YES

UVM performs physicals or other eligibility testing to be sent to investigators at another site.

UVM collects and reports data to investigators at another site.

Contracted Medical/ Professional Services

UVM performs physicals or other eligibility testing to be sent to investigators at another site.

NO
UVM must adhere to commonly recognized professional standards for maintaining privacy and confidentiality.

YES

UVM performs and/or analyzes blood draw for genetics study occurring at other institution and furnishes the results to the investigator.

UVM collects and reports data to investigators at another site.

Consulting Services

Consultant does not obtain, receive or possess identifiable private information (e.g., the consultant analyzes data that cannot be linked to individual subjects, directly or through a coding system, by any member of the research team).

NO

YES

Consultant accesses or uses identifiable private information while visiting the research team's institution.

NO
But consultant's activities become subject to the other institution's IRB.

YES

Consultant obtains coded data for analysis at UVM (and there is not a written agreement unequivocally prohibiting release of identifying codes to the consultant).

YES

YES

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4. IRB Review Determinations 46.109 and 46.113

The IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by this policy, including exempt research activities under § __.104 for which limited IRB review is a condition of exemption (under § __.104(d)(2)(iii), (d)(3)(i)(C), and (d)(7), and (8)).

Approved

This decision indicates that the initial review of a research project at a convened meeting or via expedited review has been approved without requiring either further (a) changes to the protocol or informed consent document(s), or (b) submission of clarifications or additional documents.

Modifications Required for Initial Approval

This decision indicates approval is pending satisfactory resolution of conditions or clarifications that the IRB requires to approve the project. Under this scenario, for full review protocols, further review by the IRB at a subsequent convened meeting is not necessary to secure final approval.

The expedited review process is employed to review the response from the investigator. The IRB directs that the IRB chairperson (or other individual(s)) to review and determine on behalf of the IRB whether the changes, clarifications, and/or additional documents to be submitted by the investigator(s) are satisfactory.

If under the expedited review of the response, the IRB chairperson (designated reviewer) is unable to approve the project because he/she cannot make the determinations required for approval, they can either refer the project to the IRB for further review and action at a convened meeting, or defer approval of the research project and require that the investigator (a) make changes to the protocol or informed consent documents, or (b) submit clarifications or additional documents prior to further review by the IRB chairperson (or designated reviewer(s)). 

Tabled

This action is taken under full Committee review any time the IRB cannot make one or more of the determinations required for approval by the HHS regulations at 45 CFR 46.111 and, if applicable, subparts B, C, or D of 45 CFR part 46, but with revisions may be found to be approvable.

When tabling a project, the IRB, under its authority to require modifications in order for an investigator to secure approval, may require that the investigator (a) make changes to the protocol or informed consent documents, or (b) submit clarifications or additional documents.  The research may not proceed until the IRB reviews, at a subsequent convened meeting, the revised research project and approves it.

Disapproved

This action is taken under full Committee review when the determinations required for approval of the research cannot be made, even with substantive clarifications or modifications to the protocol and/or informed consent/process/document.

If the IRB decides to disapprove a research project, it will include in its written notification a statement of the reasons for its decision, based on specific federal regulatory criteria.

Administrative Holds, Suspensions or Terminations 46.113

All currently approved research is subject to modification or change in approval status, as deemed necessary by the IRB. The IRB has the authority to suspend or terminate research for not being conducted in accordance with State and Federal laws/regulations, and/or IRB requirements, policies and procedures; or if it has been associated with unexpected serious harm to subjects. The Investigator also has the option to place the research on administrative hold. See section Administrative Hold, Suspension, or Termination of IRB Approval.

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4.1. Administrative Hold, Suspension, or Termination of IRB-Approved Approvals

The IRBs have the authority to suspend or terminate their approval of research that is not being conducted in accordance with IRB requirements or federal regulations, when the research is associated with unexpected serious harm to research participants or others or when there are immediate serious issues involving participant and/or others safety. 45 CFR 46.113.

An investigator may also place a voluntary administrative hold on previously approved research when in the judgment of the investigator an administrative hold is appropriate to protect the rights or welfare of participants.

In this policy, the IRB designee refers to the following: The IRB Executive Chair, IRB Chair, Associate IRB Chair, IRB Director, and Institutional Official.

Administrative Hold

An administrative hold is a voluntary action by an investigator to temporarily or permanently stop some or all approved research activities. Administrative holds are not considered suspensions or terminations, and do not meet reporting requirements to OHRP, FDA and other federal agencies. Administrative holds must not be used to avoid reporting deficiencies or circumstances that otherwise require reporting to federal agencies.

1. Investigator can place an administrative hold on research if; a complaint is received; an allegation of non-compliance is reported to the IRB; a discovery by the investigator of potential additional risk to subjects; or a potential change in the rights or welfare of subjects.

2. Investigator must notify the IRB in writing when exercising the option for administrative hold. The Investigator could place specific activities on hold, such as a hold on recruitment; hold on screening/enrollment; hold on interactions/interventions with subjects; and/or hold on collection or analysis of private identifiable information about subjects.

3. Investigator must address the effect of the administrative hold on the rights and welfare of the current subjects.

4. Investigator must promptly notify the IRB in writing of the intention to remove the administrative hold prior to implementing the action.

During administrative hold, the research remains subject to continuing review and requirements for reporting non-compliance and unanticipated problems involving risks to subjects or others.

The IRB designee may make recommendations for additional education and/or compliance interventions for the Investigator and research personnel. At any point, the IRB Committee can suspend the research, which will result in required regulatory reporting.

Suspension

A suspension of IRB approval is a directive of the convened IRB, or IRB designee either to stop temporarily some or all previously approved research activities, or to stop permanently some or all previously approved research activities. All suspensions are immediately reportable to OHRP, FDA and other federal agencies applicable.

Examples include; an unanticipated problem in research involving greater than minimal risks to subjects or others; new information becomes available that could alter the original determination by the IRB to approve the study; (unexpected serious harm to subjects) or the PI fails or appears to fail to comply with federal regulations or UVM policy regarding the protection of human subjects.

The IRB designee has the authority to suspend previously approved research when required for the urgent protection of the rights and welfare of participants and insufficient time exists for the convened IRB to review the event. Any suspension of research by the above individuals is placed on the next available agenda, reviewed and upheld, overturned or supplemented by the convened IRB at their meeting.

During suspension, the research remains subject to continuing review and requirements for reporting non-compliance and unanticipated problems involving risk to subjects or others.

The IRB Chair or designee notifies the investigator of the suspension and the reason for the suspension.

Safety concerns are reviewed through the Safety Subcommittee process and noncompliance issues are reviewed following the Noncompliance Policy and Procedures.

Termination

A termination of IRB approval is a directive of the convened IRB or IRB designee to permanently stop all previously approved research activities. All terminations are reportable to OHRP, FDA and other federal agencies applicable. Protocol approval will not be terminated without first undergoing temporary suspension and completion of a review through the Safety Subcommittee process or the Noncompliance Policy and Procedures.

Previously approved research may only be terminated by the convened IRB, including protocols originally approved under expedited procedures.

Terminated protocols are considered closed and no longer require continuing review.

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5. Investigator Responsibilities

Eligibility requirements for conducting human subjects research vary depending on the role of the researcher. Research personnel must be appropriately qualified by training and/or experience to perform their research responsibilities.

Principal Investigator

The Principal Investigator (PI) is ultimately responsible for assuring compliance with applicable University IRB policies and procedures, DHHS Federal Policy Regulations, and FDA regulations and for the oversight of the research study and the informed consent process. Although the PI may delegate tasks to members of his/her research team, s/he retains the ultimate responsibility for the conduct of the study.

Because PI responsibilities involve direct interaction and supervision of the research team, the PI must be a current employee or student of the University and/or UVMMC who is operating within their University or UVMMC role to oversee the conduct of the study. PIs leaving the institution are responsible for notifying the IRB well in advance of their departure so that they can make arrangements to either close the study or name another appropriately qualified individual currently at the institution to serve as the PI. See manual section on Managing Research Prior to Departure.

The following individuals may serve as PI:

  • Faculty members: All categories of compensated faculty members may serve as PI if their School allows them to serve as Principal Investigator on applications for sponsored funding administered through the University.
  • Non-Faculty: A non-faculty researcher includes, but is not limited to, any of the following: fellow, resident, post-doctoral fellow, post-doctoral associate, post-doctoral trainee, and any student (graduate or undergraduate). Non-faculty researchers cannot conduct human subject research without having a faculty sponsor who is responsible for overseeing the conduct of the research activities. The faculty sponsor must be employed by the institution (UVM or UVM Medical Center.)
  • Staff: Other University or UVMMC staff may serve in this role if they have appropriate qualifications to conduct the research and if they have obtained approval to conduct the research from their immediate supervisor.
  • Students: Students may serve as principal investigators for their own research projects and are responsible for submitting the IRB application.  However, when a student is listed as the PI, a faculty sponsor must be listed on the protocol submission.

Note:The IRB reviews and holds student research projects to the same standards as human subject research conducted by faculty or staff. IRB approval or exemption must be obtained prior to initiating any research activity under IRB oversight. “Retroactive” IRB approval or exemption is not permitted under federal regulations and University policy. Failure to obtain IRB approval for research with human subjects may preclude the use of the previously collected data and could result in other institutional sanctions.

Key Personnel

Key personnel are individuals who contribute to the scientific development or execution of a project in a substantive, measurable way, whether or not they receive salaries or compensation under the protocol. This includes, but is not limited to, individuals involved in conducting the research with human subjects through an interaction or intervention for research purposes, including participating in the consent process by either leading it or contributing to it; and those who are directly involved with recording or processing identifiable private information, including protected health information, related to those subjects for the purpose of conducting the research study.

Individuals who are Not Key Personnel: An individual who will be interacting with research subjects during the course of a research study, but only in his/her regular non-research employment capacity, such as a clinic receptionist, nurse or phlebotomist, or a radiologist or radiology technician, should not be listed as Key Personnel for the study if the person will perform only genuinely non-collaborative services meriting neither professional recognition nor publication privileges and not associated with individual financial gain, and will not contribute to the design, governance and/or analysis of the study.

Key personnel must complete required training and be listed as a member of the study team.

Faculty Sponsor

All research conducted by students/trainees, including postdoctoral fellows, must include a faculty sponsor as a member of the study team. In addition to the expectation that the faculty sponsor provide active mentorship to the student during the conduct of the research, the faculty sponsor shares responsibility with the student/trainee researcher for the ethical conduct of the research and is institutionally accountable for the study.

Students/Trainees

Supervision by faculty sponsors is required for any research performed by students/trainees in any role, to ensure proper conduct of research and protection of subject rights and welfare.

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5.1 Responsibilities of Principal Investigators

The PI has primary responsibility for protecting the rights and welfare of human subjects in research. The PI’s primary responsibilities includes, but is not limited to, the following:

1.  Delegation of Responsibilities

PIs must personally perform or delegate to qualified co-investigators or research staff all of the necessary tasks to carry out their studies.  Even when specific tasks are delegated, the PI remains ultimately responsible for proper conduct of the study and fulfillment of all associated obligations.

2. Oversight of Research Team

The PI must provide members of the research team with sufficient oversight, training and information to facilitate appropriate safety procedures and protocol adherence. In addition, the IRB must be informed if a PI is no longer able to fulfill his or her duties for any reason including, but not limited to, traveling for a prolonged period of time. See PI Managing Research prior to Departure…

3. Knowledge of Human Research Protection Standards

The PI and all key personnel (together referred to as “researchers” or the “research team”) are expected to be knowledgeable about and comply with the requirements of each of the following: 

  • The Common Rule (opens in a new window) and other federal research laws and regulations;
  • Applicable state law;
  • The University’s Federalwide Assurance;
  • Institutional policies and procedures for the protection of human subjects and reporting and managing conflicts of interest; 
  • The terms and conditions of any research agreements (with government or private sponsors); and
  • The basic ethical principles that guide human subjects research.

Institutional policies and procedures include these IRB Operating Procedures, as well as policies and procedures maintained by the academic units to which researchers and research staff are appointed, and the policies and procedures of other research review units with relevant oversight responsibilities, such as UVMMC Billing Compliance, the Institutional Biosafety Committee, etc. See Coordination with Other Compliance Committees.

4. Evaluation of Adequacy of Resources

PIs must ensure that adequate resources (facilities, equipment, supplies, and personnel) exist to:

  • Conduct the research (e.g., through internal or external funding for staff, facilities and equipment);
  • Protect subjects; and
  • Ensure the integrity of the research.

5. Training Requirements

Researchers must complete educational training as required by the University, the relevant IRB, and other review units prior to initiating research, and should not undertake responsibility for human subjects studies unless they understand these requirements and are willing to be held accountable for complying with the relevant standards and protecting the rights and welfare of research participants. For additional information refer to Training Requirements.

6. Conflict of Interest Disclosures

Financial conflicts of interest relating to human subjects research must be disclosed. Such conflicts of interest are not inherently wrong, and as long as they are disclosed and appropriately managed or resolved, they do not distort and can benefit the research process. A conflict of interest may arise when a faculty or staff member has a relationship with an outside organization that puts the faculty or staff member in a position to influence the university's decisions in ways that could lead directly or indirectly to financial gain for the faculty or staff member or his or her family, or give improper advantage to others to the detriment of the University. 

7. ClinicalTrials.gov Registration

Certain clinical studies involving human subjects must be registered on and have results posted in ClinicalTrials.gov.  Please review the link below to find step by step instructions on registering your study.

PDF icon Clinical Trials Registration Information - Last updated October 18, 2018 (PDF)

8. Studies Regulated By the Food and Drug Administration

When conducting research involving FDA-regulated products, researchers must comply with all applicable FDA regulations and fulfill all investigator responsibilities or all sponsor-investigator responsibilities, as applicable.

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5.2 Key Personnel Responsibilities

This is a general guide and does not contain a comprehensive description of all of the potential responsibilities of a member of the research team (key personnel).

1. Minimizing Risks to Subjects and Protecting Subject Rights and Welfare

Federal regulations, institutional policy, and guiding ethical standards require that human subjects research be designed to minimize risks to participants. Minimizing risks and protecting human research subjects take precedence over the goals and other requirements of any research endeavor.

2. Obtaining and Documenting Informed Consent

Informed consent must be obtained from and documented for each prospective research subject (or the subject’s legally authorized representative) before the subject begins to participate in the research (including any related eligibility testing not conducted solely for clinical purposes), unless the appropriate IRB has approved a waiver or alteration of consent, or waiver of documentation.

Informed consent is not a single event or document, but an ongoing process that takes place between the investigator (or other key personnel, as appropriate) and the research subject. Informed consent requires full disclosure of the nature of the research and the subject’s participation, adequate understanding on the part of the subject (or the subject’s legally authorized representative), and the subject’s voluntary decision to participate.

3. Compliance With IRB and Other Requirements

An IRB must review and approve all research activities that meet the definition of human subjects research before they are initiated, unless an IRB has determined that the activities are exempt from IRB oversight. For non-exempt research, the IRB is also responsible for review and approval of continuing review, progress reports, change of protocol, adverse event reporting, Other Reportable Information or Occurrence (ORIO) reporting, monitoring and record keeping. Researchers must at all times cooperate with the IRB in fulfilling its responsibilities.

4. Conflict of Interest Disclosures

Financial conflicts of interest relating to human subjects research must be disclosed. Such conflicts of interest are not inherently wrong, and as long as they are disclosed and appropriately managed or resolved, they do not distort and can benefit the research process. A conflict of interest may arise when a faculty or staff member has a relationship with an outside organization that puts the faculty or staff member in a position to influence the university's decisions in ways that could lead directly or indirectly to financial gain for the faculty or staff member or his or her family, or give improper advantage to others to the detriment of the University. 

5. Studies Regulated By the Food and Drug Administration

When conducting research involving FDA-regulated products, researchers must comply with all applicable FDA regulations and fulfill all investigator responsibilities or all sponsor-investigator responsibilities, as applicable.

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5.3 Access To and Retention of Research Records

Access to Research Records

The investigator must provide direct access to all research records to the IRB staff. Dependent upon the protocol sponsorship there may be others with access needs, such as study monitors, FDA, and other regulatory authorities. There may be other units internally (e.g., OCTR, UVMCC, CRC, UVM Medical Center Risk Management) with oversight responsibilities that must be granted access as well.

NOTE: Unless otherwise indicated in a protocol and/or consent form, a subject’s specific research data is generally not provided to the research subject or his/her representative.

Retention of Research Records

The regulatory mandated duration for records retention varies depending on which regulations apply to the research in question. UVM investigators need to ensure that their plan for record retention complies with the federal regulations as well as UVM Records Retention policy (PDF).

  • *IRB Records means all records of communications with the IRB and all approval documents.
  • *HIPAA Waiver means the record of the IRB determination of a waiver of authorization.
  • **Research Records (subject study file) refers to documentation of all observations and other data pertinent to the investigation on each individual in the investigation.
  • **HIPAA Authorization means either the executed consent form, separate authorization or documentation of verbal authorization.

*Captured by the IRB within the electronic submission software.

**PI’s responsibility to ensure retention requirements are met.

Research Not Regulated by the FDA

45 CFR 46.115(b) (opens in a new window) (DHHS) requires that all IRB records be retained for at least 3 years, and research records be retained for at least 3 years after completion of the research. All records must be accessible for inspection and copying by authorized representatives of HHS at reasonable times and in a reasonable manner.

UVM policy requires that the IRB and investigator maintain records for 6 years due to the extended retention period required by HIPAA (see below).

Research Regulated by the FDA (Drug and Device)

21 CFR 312.62(c): (opens in a new window) An investigator involved in the research of drugs, devices, or biologics being tested in humans for FDA approval shall retain records

  • for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and FDA is notified.
  • The date of last marketing approval will not be known at the time the research is completed and can be quite long. Investigators are advised to include funds for storage of the case records in their study budget. Records should be retained until there is written confirmation from the sponsor or FDA granting permission to destroy them.

UVM policy requires that the IRB and investigator maintain records for 6 years due to the extended retention period required by HIPAA (see below).

Research Which Includes Protected Health Information (HIPAA Requirements)

45 CFR 164.530(j)(1) (opens in a new window) HIPAA requires a 6 year retention period for the documents listed below.

  • Written HIPAA Authorizations: If the research involves Protected Health Information (PHI), the Principal Investigator must retain the permission (i.e. the consent form or authorization) to use the PHI for 6 years beyond the expiration date of the authorization (completion of the research).
  • IRB Determinations for Waiver of HIPAA: Records documenting that a request for waiver of HIPAA Authorization met all the requirements of 45 CFR 164.512(i.)(2)(ii) must be retained for 6 years from the completion of the research. This information will be archived in the IRB electronic system.
  • Disclosures of PHI: An accounting of all disclosures of PHI must be retained for 6 years after the disclosure. Retaining the disclosures is a responsibility of both the PI and the hospital.

UVM policy requires that the IRB and investigator maintain records for 6 years due to the extended retention period required by HIPAA.

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5.4 Training Requirements

The University of Vermont and UVM Medical Center have pledged a commitment to the protection of all human subjects in research and have a long-standing history in extending protections required by federal funding to all research activities. In keeping with this commitment, completion of the UVM and UVM Medical Center approved human subjects training is required for all individuals involved in the conduct of research involving human subjects, regardless of funding source.

The IRB will not release the approvals for new protocols until all individuals involved with human subjects on the project (i.e., direct contact with subjects or access to data) have completed the required training as listed below. Additionally, no new personnel will be added to the protocol until the required training is complete.

The principal investigator is also responsible for ensuring that the research team has appropriate protocol specific training prior to and during the conduct of the study. Dependent upon delegated responsibilities, this training could take the form of attendance at investigator meetings, regular local research team meetings, or daily mentorship from the principal investigator.

Human Subjects in Research Training

Please reference the CITI Program Training page on our website for additional information about required human subjects in research training. Refreshers are required every three years.

Good Clinical Practice Training

Good Clinical Practices (GCP) training must be completed if working on a study that meets the NIH definition of a Clinical Trial. Please reference the CITI Program Training page on our website for additional information about GCP training. Refreshers are required every three years.

Who is Required to Complete Training

  • Principal Investigators on all protocols including exempt
  • Key Personnel listed on active nonexempt protocols*
  • Faculty Sponsors
  • Class Instructors

*While key personnel working on exempt projects are not required to complete the human subjects training, completion is strongly recommended. Not research and not human subjects projects do not require key personnel to complete training.

Documentation of Completion

Documentation of training completions are located on our Tutorial Completion page.

Training Expiration

Applicable training requirements must be renewed every three years. Reminders of impending expiration are sent to the individual as the anniversary nears. If a PI’s training expires, this will result in the withdrawal of protocol approval.  Protocol related research activities must stop until training is complete and protocol approval is re-instituted.  If the study is a treatment trial and withholding the treatment is not in the best interest of the subjects, the PI must contact the Research Protections Office immediately to determine the appropriate action.

If a Faculty Sponsor’s training expires, the PI must find an alternate Faculty Sponsor until the training is complete.  The individual has 30 days to find an alternate sponsor or his/her approval will be withdrawn as well.

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5.5 Guidance on Data Management in Human Subjects Research

Background

This guidance is intended to assist researchers in developing data management plans for human research data. The guidance presents relevant definitions and key concepts concerning human research data, describes the roles and responsibilities for data management, outlines the elements of a research data management plan, and describes requirements for maintaining and using human research information once projects are completed.

The protection of privacy and the confidentiality of information about research subjects is a special concern for IRBs in their review of research data management. Research subjects must have a reasonable expectation that personal information will be disclosed only with their permission or in ways that are consistent with the consent process, and in compliance with the laws and regulations. Violations of confidentiality could have serious consequences for research subjects, including potential discrimination, misuse of genetic information, loss of insurance, or loss of privacy. Even with all the appropriate state and federal laws, University and hospital policies, and requirements of IRBs all aimed at protecting the confidentiality of a research subject’s individually identifiable private information, violations of privacy can and do occur. Such violations may be inadvertent (accidental) or due to carelessness, deliberate or compelled by regulation or law.

Clearly defined and faithfully followed procedures to protect the confidentiality of human subjects can significantly reduce the possibility of violations to the confidentiality of human research data and should be part of every study design.

In addition to this guidance, researchers may need technical support from either UVM’s Enterprise Technology Services (ETS) or the College of Medicine Technology Services (COMTS) for assistance with development of an adequate research data protection protocol. Contacts are listed below.

UVM Information Security Operations Team

iso@uvm.edu

COM IT Information Security

infosecurity@med.uvm.edu

University of Vermont (UVM) policies referenced in this document:

Information Security Procedures (PDF)

Intellectual Property (PDF)

UVM Medical Center policies:

UVMMC employees may view related policies on the UVMMC Intranet.

Please note that the information in this guidance was current when the guidance was issued Summer 2015. As technologies and social norms advance, however, the standards for managing data may change.

Definitions and Key Concepts

Anonymization

This process removes information from data that allows recognition of particular individuals. Common strategies for anonymizing data are deleting or masking personal identifiers, such as name and social security number, and suppressing or generalizing quasi-identifiers, such as date of birth and zip code. Cell size restrictions may also be applied. Typically anonymized data is not coded; it ordinarily contains no link to individually identifying information that may be available to the researcher. Information that was previously recorded or collected without any of the 18 identifiers as defined by HIPAA, and no code is assigned that would allow data to be traced to an individual.

Coding

Coding is a process in which individually identifying information is replaced with a number, letter, symbol, or combination thereof and a key linking the code to identifiers is created. The key is usually maintained separately from the coded data. Coding is one means to protect the confidentiality of research data.

The HIPAA Privacy Rule requires that a code for the re-identification of health information does not derive from or be related to identifiers for an individual and not be capable of translation to identify an individual. This requirement can eliminate the use of so-called hash codes.

Confidentiality

Confidentiality means restricting access to information that an individual has disclosed in circumstances that the individual can reasonably expect the information will not be made public. The relationship between a researcher and a study participant is ordinarily one of trust. This relationship often includes an expectation that personal information collected for research that is ordinarily regarded as private will not be divulged outside the research team without explicit permission or in ways that are inconsistent with consent to research participation.

Covered Entity

Those entities to which HIPAA Privacy Rule standards apply are called “covered entities”. They are defined as (1) health insurance plans, (2) health care clearinghouses, and (3) health care providers that electronically transmit health information in connection with medical service transactions.

Data

The Merriam-Webster Dictionary (2005) defines data as "factual information (as measurements or statistics) used as a basis for reasoning, discussion, or calculation." There are many ways to categorize data; for the purpose of this guidance, the terms as used in this document are described below.

Research data refers to collected and recorded factual information commonly accepted in scientific and scholarly communities as necessary to validate research findings. Research data can be classified as:

  • Anonymous research data: Research data that lacks information that would allow the recognition of particular individuals by the researcher.
  • Health data: Health information created or received by health care providers, insurance plans, and clearinghouses that is individually identifiable is protected by federal and state laws, including the Health Insurance Portability and Accountability Act of 1996 (HIPAA; see the definition below.).
  • Identifiable biospecimen/identifiable private information. An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.
  • Identifiable research data: Research data containing information that allows recognition of particular individuals from the data by the researcher.
  • Indirectly identifiable research data: Research data that are coded with a key linking the data to individually identifying information. The key may or may not be available to the researcher.
  • Limited data set: See the definition below.
  • Processed research data: Analyses, descriptions, and conclusions prepared as reports, manuscripts, theses, or papers.
  • Published research data: Written information distributed to people beyond those involved in research data acquisition.
  • Raw or primary research data: Information recorded as notes, images, video recordings, paper surveys, computer files, etc., pertaining to a specific research project. Examples of such data are: survey responses, observations of behaviors, observations of medical symptoms, temperature readings, behavioral or medical test results, biological samples, and radiographic images.

De-Identification

As required by the HIPAA Privacy Rule, this process involves the removal of the following informational elements from health information.

1. Names.

2. All geographic subdivisions smaller than a state, including street address, city, county, precinct, ZIP Code, and their equivalent geocodes, except for the initial three digits of a ZIP Code if, according to the current publicly available data from the Bureau of the Census:

  • The geographic unit formed by combining all ZIP Codes with the same three initial digits contains more than 20,000 people, and
  • The initial three digits of a ZIP Code for all such geographic units containing 20,000 or fewer people are changed to 000.

3. All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older. The population of a zip code can be identified on the web site of the U.S. Census Bureau.

4. Telephone numbers.

5. Facsimile numbers.

6. Electronic mail addresses.

7. Social security numbers.

8. Medical record numbers.

9. Health insurance plan beneficiary numbers.

10. Account numbers.

11. Certificate/license numbers.

12. Vehicle identifiers and serial numbers, including license plate numbers.

13. Device identifiers and serial numbers.

14. Web universal resource locators (URLs).

15. Internet protocol (IP) address numbers.

16. Biometric identifiers, including fingerprints and voiceprints.

17. Full-face photographic images and any comparable images.

18. Any other unique identifying number, characteristic, or code, unless permitted by the HIPAA Privacy Rule standard for re-identification.

In addition, health information can be de-identified if (a) a person with appropriate knowledge of and experience with generally accepted statistical and scientific principles and methods determines that the risk is very small that the health information could be used to identify an individual and documents the methods and results of this analysis, or (b) the covered entity from which health information is being obtained does not have actual knowledge that the information could be used to identify an individual.

Encryption

Encryption is the process of comprehensively encoding information in such a way that only authorized parties can read it. Encryption limits access to data by controlling the distribution of the decoding algorithm to authorized individuals. Encryption is one means of protecting the confidentiality of research data. Under HIPAA, if protected health information is encrypted, this action provides a “safe harbor” from violating HIPAA.

Health Insurance and Portability and Accountability Act of 1996 (HIPAA)

HIPAA is federal legislation that, along with its implementing regulations, produced legal protections for health information. This legislation has had an impact on the conduct of research involving health information. A critical part of HIPAA for research activities is the so-called privacy regulations, often referred to as the Privacy Rule. The intent of the HIPAA Privacy Rule is to protect the confidentiality of health care information and define the rights of patients regarding their health information. The HIPAA Privacy Rule created the concept of “protected health information” or “PHI”, which is individually identifiable health information created or received by a covered entity (See the definition of covered entity above.)

Under the HIPAA Privacy Rule, specific permission from patients for research use of health information may be obtained using an Authorization in addition to the consent process. The HIPAA Privacy Rule specifies the kinds of information included a the Authorization language. Provided certain regulatory criteria are satisfied, an IRB may waive or alter the information included in the Authorization language.

Honest Broker

An honest broker obtains legally protected data from their source and typically codes and then de-identifies the data or creates a limited data set for research use. The honest broker retains the key linking the code to identifiers for individual contributors of the data. If questions arise about the validity or accuracy of the data, the honest broker can typically resolve them without revealing the identity of individuals to the researcher. As a result of the activities of the honest broker, the research conducted with processed data may not involve human subjects, because the data lacks identifiable private information.

An investigator actively involved in the research in which the data are used cannot be an honest broker, nor can any person under the investigator’s supervision.

Identifiers

Identifiers are specific informational elements that permit the recognition of a particular person.

Limited Data Set

Under the HIPAA Privacy Rule, a limited data set is defined as protected health information that excludes the aforementioned direct identifiers of an individual or of relatives, employers, or household members of that individual.

A limited data set may only be used for the purposes of research, public health, or health care operations.

A data use agreement between the source of the protected health information and the recipient is needed for use of a limited data set. This agreement restricts the uses and disclosures of the limited data set, requires the recipient to establish appropriate safeguards to limit further uses and disclosures, applies the HIPAA Privacy Rule to the use of the limited data set, and prohibits identifying or contact with the individuals who contributed the data.

Repository

A repository compiles data, specimens, or both for future research purposes. The repository receives, processes, stores, and distributes data with or without specimens to researchers. The repository may or may not be an honest broker.

Sensitive Data

Data that are individually identifiable and private usually are considered sensitive and should be protected appropriately. Identifiable data that if disclosed could have adverse consequences for subjects or could damage their financial standing, employability, insurability, or reputation are considered highly sensitive. The IRB may recommend that a Certificate of Confidentiality be applied in these cases to allow researchers to refuse to disclose names or other identifying characteristics of research subjects in response to legal demands. A list of research in which resultant data would be considered highly sensitive can be found in Appendix M., Section 1. Very stringent security precautions need to be in place to protect research data while in storage or being transferred.

Roles and Responsibilities for Human Subject Data Management

Principal Investigators (PIs)

PIs are responsible for developing an appropriate data management plan as well as ensuring that research staff members are thoroughly trained to maintain the integrity of the research data that is collected. These responsibilities include determining how to best collect, store, protect, analyze, and disseminate research data.

Research Team Members

The primary research data management responsibilities of research coordinators, research assistants, and those in similar positions are usually involved with research data collection, ensuring the reliable and accurate collection of the research data and protecting the confidentiality of research data that are collected.

Statisticians are primarily responsible for ensuring comprehensive and appropriate research data analysis.

The Institutional Review Boards (IRBs)

The IRBs are responsible for review and approval of proposed data management plans so that the rights and welfare of research subjects are acceptably protected.

The Research Data Management Plan

A summary of four basic types of research data appears in the table below.

DIRECTLY IDENTIFIABLE RESEARCH DATA

INDIRECTLY IDENTIFIABLE RESEARCH DATA

ANONYMIZED RESEARCH DATA

DE-IDENTIFIED RESEARCH DATA

Data contains informational elements that allow the data to be associated with a living unique individual.

Direct identifiers among the data are replaced by a code and a key to the code links it to individual identities. Re-identification of the data is possible.

Individual identifiers were never recorded or have been stripped from the dataset and the data has been manipulated to make it very difficult to re-identify individuals. The data is not coded.

Certain specified informational elements are absent from the data. The data may or may not be coded.

Before starting a new scientific research project, the PI and research team should address the following activities related to research data management.

Data Collection

The information below is intended as general advice to researchers about devising a data management plan.

The data management plan should reflect whether or not the project requires that data to include

  • Direct identifiers,
  • If a code should be used, resulting in indirectly identifiable data,
  • If the research data should be anonymized, or
  • If the data should be collected without any identifiers at all.

The use of identifiers should have a clear justification, because it will increase risks to the confidentiality of subject data. If the research data is coded, the plan should describe the coding methodology, and the security arrangements for storage of the “key” linking the code to identifiers. In general, the key should be stored separately from the data.

Data Storage

Researchers should decide how they are going to store research data, in what format, and for how long. Considerations should include the data retention requirements of UVM and UVMMC, sponsors, and publishers, plus intellectual property protection, and potential data sharing.

Generally speaking, enough research data should be retained so that the findings of a project can be reconstructed with ease. While this does not mean that a project needs to retain all the raw research data that were collected, relevant statistics and analyses from this research data should be saved, along with any notes or observations.

Some key issues for electronic research data storage are: (1) thorough documentation to allow research data to be appropriately used in the future and (2) using storage formats that are adaptable to evolving computer hardware and software. There are also some additional considerations that are unique to electronic research data storage, including rapid access to the data, fast read/write rates, ability to archive and remove the data, low cost, and a backup system.

Data Retention and Disposal

Research sponsor requirements, clinical trial contracts, federal grant terms and conditions, data sharing plans, intellectual property protection, publishers’ policies, and the potential future value of the research data often require long retention periods. In addition, UVMMC’s policies apply to clinical care and other health services delivery data. In general, the UVM Records Retention policy (PDF) applies.

The IRB strongly recommends that researchers remove direct identifiers, such as those listed in the HIPAA Privacy Rule standard for de-identification, so that the identity of individual research subjects cannot be readily ascertained from the data. Additionally, researchers should arrange to securely archive signed consent forms. Such procedures for stored research data serve to minimize risks to subjects. The IRB review process includes asking researchers to describe their plans and procedures for long-term maintenance of research data involving human subjects when study protocols are closed.

Destruction of Research Data

When researchers decide that research data should no longer be maintained, the data should be thoroughly and completely destroyed. Effective destruction ensures that research data cannot be extracted or reconstructed. Many document storage companies now offer onsite shredding and secure destruction of written and electronic media.

For electronic research data, the IRB advises researchers to contact either the College of Medicine Technology Services COMTS or Enterprise Technology Services (ETS) to assist with development of an adequate data destruction plan, as simply deleting the data files is insufficient.

Data Security

Research data management plans should ensure that hard copy and electronic research data are securely stored to prevent unauthorized access, disclosure, or loss. Hard copy records should be stored in a manner that limits access to authorized individuals. For example, filing cabinets/areas should be locked and placed in rooms that are routinely locked when not in use.

Electronic research data should be stored on a device that has appropriate security safeguards, such as unique identification of authorized users, password protection, encryption, automated operating system patch (bug fix) management, anti-virus controls, firewall configuration, and scheduled and automatic backups to protect against research data loss or theft. If a researcher chooses to store directly identifiable private research data locally on the computer’s hard drive, that computer, whether a laptop or desktop, must be encrypted. The use of the network and servers maintained by the University is preferable to saving data on a local hard drive.

Laptops, Smart Phones, Tablets, removable hard drives, “jump” or “thumb” or “flash” drives, CDs, DVDs, and other portable devices and removable media are convenient to ensure your research data are always at your fingertips.  External hard drives are a cost effective and convenient way to back up your research data. These devices, however, require encryption solutions if they are used to store or transfer directly identifiable private information.  This requirement may be waived depending upon the sensitivity of the data being collected. The IRB will make that determination.

Because email is not secure, directly identifiable private research data that will be transferred via email, requires that the data file be encrypted prior to sending.

The IRB advises researchers to refer to the University Information Security Procedures Policy or to contact the appropriate technical support from either the College of Medicine Technology Services (COMTS) or Enterprise Technology Services (ETS) for assistance with development of an adequate research data protection protocol.

Data Analysis and IRB Approval

Primary Analysis

Primary analysis refers to how raw research data are chosen, evaluated, and interpreted into meaningful and significant conclusions. Once the primary research data analysis for a protocol is complete, the protocol should be closed with the IRB. Any subsequent analysis of the same research data, however, is usually considered secondary research data analysis.

During analysis, when subjects are typically no longer being enrolled, a researcher may apply for IRB approval to anonymize the research data by completing a continuing review application describing how identifiers will be removed. When the IRB approves a proposal to remove identifiers from remaining research data, IRB oversight of the study stops, and the researcher may continue to analyze the now anonymized research data.

Secondary Analysis

Any new, subsequent secondary analysis of existing human subject research data either requires: 1) IRB review and approval prior to access to or access to the research data; or 2) an IRB determination that its review is not necessary. See the chart below.

The IRB is responsible for determining whether or not 1) secondary analysis of research data increases risks to subjects, and 2) subjects were adequately informed during the original consent process about the possibility of secondary research use, maintenance of confidentiality, and destruction of identifiers. Based on these determinations the IRB may require the investigator to obtain informed consent from the subjects for secondary analysis.

Unless a dataset is anonymous, namely contains no direct identifiers and no code linked to identifiers, investigators who obtain research data from other researchers for secondary analysis should obtain IRB review and approval, or the IRB’s determination that the research does not require further IRB review, prior to obtaining the research data. The researcher providing the data may need to consult with his or her institution before sharing research data with local investigators. Guidance about data acquisition, management, sharing, and ownership at UVM can be found on the Sponsored Project Administration web page.

 

IRB REVIEW OF ADDITIONAL DATA ANALYSIS

AFTER INITIAL PROTOCOL APPROVAL

Does The Research Data Have Identifiers?

Proposed New Analysis Plan

Requirement For IRB Review

No

Change to analysis of anonymous or anonymized data in an existing research project

No

Yes

Change to data analysis for a currently approved research protocol.

Submit an amendment to original study for IRB review of the proposed modifications

Likely to qualify for Expedited Review unless risks to subjects would be increased.

Yes

Analysis of research data from previously approved research after the original study is closed.

Submit a new application for IRB review with a protocol describing the research data and its analysis plan. Include a copy of the IRB approval letter and IRB approved consent form for the original study that collected the data.

Note: If the original IRB approved protocol and consent did not include information about the new proposed analysis, the application for review should include a procedure for obtaining consent or a request for waiver of informed consent and authorization if PHI is involved

Likely to qualify for Expedited Review unless risks to subjects would be increased.

Yes

Storage of research data to share with colleagues or students in the future.

Submit a new application for review of a repository.

 

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5.6 Managing Research Prior to Departure, Sabbatical, Medical Leave, or Other Absence

RPO requires that a qualified PI be assigned to each protocol at all times. All investigators have the responsibility to manage the disposition of their studies before taking a leave or departing the University. Department chairs or faculty mentors are responsible to ensure that this be accomplished prior to the investigator’s leave.

Procedures for a Planned Temporary Leave of Four Weeks or More

Examples of temporary leave includes, but is not limited to: Military Leave, Extended Sick Leave

In these situations, the PI must contact the IRB Research Analyst assigned to your department to discuss the specific status of the protocol(s) to assist you in making a determination as to how best to ensure continued research compliance during the leave.

Procedures for an Unforeseen Temporary Leave of Four Weeks or More

  • The PI or their representative, such as the Department Chair or key research personnel, must immediately contact the IRB with the name of a designated investigator.
  • The PI or their representative must submit an amendment to designate an interim investigator.
  • The PI or their representative is responsible for quickly orienting key research personnel and the designee.

Procedures for Permanent Leave

Examples of permanent leave includes, but is not limited to: Graduating, Transferring to another school, indefinite break from studies at UVM, Resignation, Retirement

If intent is to close protocol

  • The PI is responsible for submitting a final report in advance of IRB approval expiration.
  • Student PIs who are graduating must submit a final report.
  • In both of these cases, the PI can meet this requirement by completing final continuing review form.

If intent is to transfer to another UVMMC/UVM PI

  • The PI must submit an amendment to appoint the new PI well in advance of their departure. PIs are encouraged to seek the assistance of their Department Chair and colleagues in this process.
  • If a faculty sponsor wishes to continue a student-led project after the student has graduated, they are responsible to identify a new PI or become the PI of record for the protocol. An amendment to update this information must occur in advance of the student’s departure.
    • In both of these cases, all protocol documents that contain the departing PI, such as the protocol, informed consent, parental permission, assent, advertisement/s, and/or recruitment material/s must be revised and submitted with the amendment for stamp.

Informing Subjects

If the departing PI will no longer be listed on a clinical study that includes a drug, device, or other intervention, active subjects (and any subject with an implantable device) should must be notified and provided with new contact information should they have questions about the research.

Key Personnel Who Remain Listed on a Protocol After They Leave

Key personnel who have left the institution must be removed from the protocol roster. If key personnel leaving the institution wish to continue to be engaged in the UVM/UVMMC research protocol, the protocol must be amended to reflect that change and they must obtain IRB review and approval of the protocol from their new institution prior to beginning activities. If their new institution does not have an IRB, the PI should contact the RPO office to discuss options early in the process.

Nine-Month Faculty Appointments

Nine-Month faculty are expected to be available during the summer months. If the PI anticipates not being available by any means, the PI must submit an amendment identifying a person who will oversee the research during that time.

Retired Faculty with Emeriti Status

The bestowal of Emerita/Emeritus status is an honor awarded to eligible individuals who have achieved a career of professional accomplishment and provided distinguished service to the University, the community, and their professional discipline or profession.

See the University’s Emeriti Status policy (PDF)

Emeriti faculty may continue to conduct research activities if they have been provided with appropriate resources and there is adequate oversight by the academic department. The IRB may request confirmation of approval from the Department Chair prior to approving research proposed by the emeriti faculty.

Additional Things to Consider When Departing the Institution

Disposition of the Research Data

PIs are responsible for data collection, maintenance, and retention of University-owned Research Data in accordance with the Access and Retention of Research Data policy.

Disposition of Biological Materials

If a researcher wishes to take biological materials collected at the University of Vermont/UVMMC to continue his/her research at another institution, the consent of the Department Chair and IRB shall first be obtained. Transfer requests are subject to all terms of funding agreements under which the tissue was collected or the bank was established. The human biological materials must be transferred pursuant to a University Material Transfer Agreement ("MTA") executed by the Office of Technology Commercialization.

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5.7 Data and Biospecimen Sharing

New Research Project

Researchers who intend to share research data or biospecimens with colleagues should be sure to include the intention to share materials within the initial protocol submission to the IRB. The IRB strongly recommends that direct identifiers be removed from the data or biospecimens prior to release; if UVM researchers intend to maintain identifiers, even if indirectly through use of a code, there should be an appropriate scientific justification for doing so included in the protocol. If there is written consent, the consent should include information about the details of what is being shared with whom and how it will be protected if directly identifiable.

Ongoing Research Project

If researchers find the need, or wish to share research data or biospecimens after the study has been IRB approved, the protocol must be amended prior to release. If a written consent exists, subjects should be re-consented to now share their data or biospecimens.

Original Research Project Closed

Research data sharing may occur after the original study has been completed. If a researcher intends to share research data or biospecimens from a study that has been closed, then the researcher should consult with the IRB. The consultation with the IRB is needed to determine whether or not the consent process for the original study included sharing. Dependent upon the consent process, data and/or biospecimens may need to be completely de-identified prior to release. The IRB will work with you on the available options.

Agreements to Address Sharing

In all cases above, UVM investigators sharing research data or biospecimens outside of the institution must enter into contractual agreements with the researchers to whom they are sending materials. If you are sending data, contact Sponsored Project Administration for further information regarding negotiation of a Data Use Agreement (DUA). If you are sharing biospecimens, contact the UVM Office of Technology Commercialization to determine if a Materials Transfer Agreement (MTA) or other agreement is needed. See Collaborative Agreements section.

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5.8 Enrollment Incentives

Enrollment incentives are any form of direct or indirect inducement (cash or non-cash) offered or received in exchange for enrolling subjects into research studies: (i) that is paid as reimbursement in excess of the reasonable cost of conducting the research protocol, or (ii) that is paid extra-contractually, including any bonus, reward, award, grant, gift, benefit, or other quid pro quo, or (iii) that creates a financial incentive that UVM and/or UVM Medical Center determine is contrary to the best interests of human subjects participating in the research.

The use of enrollment incentives in research involving human subjects creates a significant potential for conflicts of interest. Enrollment incentives are not reasonable payments made to subjects for their participation in research or to the actual costs researchers incur when enrolling subjects. Enrollment incentives are any special incentives, finders fees, bonuses or other similar forms of compensation provided to institutions or researchers as a means to encourage the enrollment of subjects in research, including clinical trials. Such incentives may create conflicts of interest. Enrollment incentives may also have an adverse effect on human subjects because such incentives may compromise the informed consent process or increase the likelihood for enrollment of ineligible persons as participants in the research.

It is the policy of the Committees on Human Research not to approve human subjects research involving use of enrollment incentives. This prohibits any payment to investigators, study personnel or departments for additional compensation that: 1) encourages the recruitment of subjects (whether it is for identification, referral, recruitment, or enrollment of any subject); or 2) is tied in any way to the rate or timeframe for recruitment or enrollment.

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6. Conflict of Interest

As an academic research institution, we must continually dedicate ourselves to the integrity of the research enterprise.

IRB Members

The IRB leadership, staff and affiliated IRB members are required to disclose significant financial interests (SFI) in accordance with University of Vermont Financial Conflict of Interest in Sponsored Research policy.

Selection of specific protocols for review by members is determined by the Committee's administrative staff and/or Chair. If an IRB member has a conflicting interest in a protocol (including, but not limited to being a principal investigator, a co-investigator, or a consultant on that protocol), that member may only provide information as requested by the IRB and will not be assigned to officially review nor vote on that protocol.

Investigators

As part of the protocol submission, investigators must inform the Institutional Review Board (IRB) whether or not they or other key personnel have a significant financial interest as defined in this policy, and must describe the nature of that interest.

Definition of significant financial interest

Significant financial interests include any monetary or in-kind payments or gifts received from the research study sponsor, including cash, consulting fees, honoraria or other payments received from the sponsor, or stocks or other ownership interests in the sponsor, if any (single) or all of the (combined) payments or ownership interests paid to or held by the Investigator in one year (including payments to or interests held by his or her spouse and dependent children) are expected to be more than $5,000 and/or constitute more than a two percent (2%) ownership interest in the sponsor. Significant financial interests also include patents, copyrights or other intellectual property rights, and royalties or other future payments to be derived from the licensing, assignment, or use of intellectual property rights, the value or amount of which could be favorably affected by the research study. The term “sponsor” as used herein shall be deemed to include any corporate parent owning a controlling interest in the corporation sponsoring the research study.

IRB Review of the Conflict

The IRB will consider and evaluate all disclosures of significant financial interests made by investigators and shall determine whether the disclosed interests could potentially compromise or influence the investigator’s professional judgment or actions in the performance of the study (e.g. the design, conduct, oversight, evaluation or reporting of the results of the study) or could otherwise adversely affect the rights and welfare of human subjects.

Financial interests determined by the IRB to have potentially negative impacts shall be deemed “relevant significant financial interests”. The IRB will take such “relevant significant financial interests” into account in determining whether to approve the study and what protocol modifications or conditions, if any, to impose on the study in order to appropriately minimize or eliminate the potential negative impacts of the financial interest. The IRB will also require that the existence of such financial interests be disclosed to study subjects.

The IRB will carefully consider specific mechanisms proposed by the investigator to minimize the potential adverse consequences of the conflict in an effort to optimally protect the interests of the research subjects. In general, he/she should not be directly engaged in those aspects of the trial that could be influenced inappropriately by that conflict. These could include: the design of the trial, monitoring the trial, obtaining the informed consent, adverse event and unanticipated problem reporting, and analyzing the data. In all cases, good judgment, openness of process, and reliance upon objective, third party oversight may effectively minimize the potential for harm to subjects and safeguard the integrity of the research.

During the course of the study, new information that falls within the reporting requirements of this policy must be disclosed to the IRB in a timely manner.

Disclosure to potential subjects

As part of the informed consent process, potential subjects will be informed of the existence of relevant significant financial interests (as defined above) held by the investigator(s). The following language (or other appropriate language approved by the IRB, in those exceptional cases meriting special language) shall be included in all informed consent forms:

“You should also know that [investigator] has a significant financial interest (e.g. a separate relationship with the sponsor or a related company involving ownership or stock, payment for services or other significant financial payments) that could potentially compromise or influence the investigator’s professional judgment or actions in the performance of the study (e.g. the design, conduct, oversight, evaluation or reporting of the results of the study). The investigator has disclosed that personal financial interest to the IRB responsible for approving this study. The IRB reviewed the [investigator’s] financial interest and determined that any potential conflicts are being appropriately managed. However, negative impacts on subjects participating in this study, are always possible, and therefore the potential conflict is being disclosed to you. Please discuss with the Investigator any questions you may have about this.”

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7. Non-Faculty Researcher Requirement

Definition

A non-faculty researcher includes, but is not limited to, any of the following: fellow, resident, post-doctoral fellow, post-doctoral associate, post-doctoral trainee, and any student (graduate or undergraduate).

Non-faculty researchers cannot conduct human subject research without having a faculty sponsor who is responsible for overseeing the conduct of the research activities. The faculty sponsor must be employed by the institution (UVM or UVM Medical Center.)

Role of the Faculty Sponsor

The faculty sponsor will assume the role of the responsible investigator on all research involving human subjects which is designed and carried out by non-faculty. The responsible investigator will advise the non-faculty researcher throughout the process of protocol development, submission, and review, as well as in the implementation of the research project. As the responsible investigator, the faculty sponsor or course instructor is required to complete the required human subjects training. Protocol approvals will not be released until that requirement has been met.

The faculty sponsor, as the responsible investigator, will guide the non-faculty researcher in the development of the protocol, thus assuring that the content, quality, and timing of the submission meet the requirements of the Committee.

Furthermore, the faculty sponsor is accountable for ensuring that non-faculty researchers are aware of their responsibilities as investigators, and for ensuring that the Committee is immediately notified in the event of research-related, unanticipated events or findings during the study that would affect the risks or benefits of participation.

Role of the Non-Faculty Researcher

Non-faculty researchers have responsibilities as listed in “Investigator Responsibilities.”

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7.1 Student Class Project Guidelines

Deciding Whether IRB Review is Necessary

The majority of classroom projects will not be considered research by Federal definition and will not require IRB review. If the intention of the class project meets the following criteria, then, the project would not meet the definition of research and does not require IRB submission.

  • It is an activity designed as part of a course requirement for purposes of learning research methods and;
  • The results and data will not be presented a research findings in any presentation, conference, publication, thesis, dissertation, or report outside of the course for which it is assigned.

If the intention is to present the outcome as research outside of the classroom, the project requires review and approval or a determination of exemption by the IRB prior to the start of project activities. As new researchers, student projects should fall into the exempt or expedited categories. Thus, instructors should encourage students to develop minimal risk protocols. The higher the risk, the stricter the regulations, which adds complexity for which the student is not prepared and which often times results in extended delays in IRB approval. Regardless of risk, the IRB process should be begin as soon as possible. Note that the IRB does not have the option of granting “retroactive” approval after research is complete; consult with the Research Protections Office for guidance prior to conducting research if there is any question.

Instructors should reference the IRB Review guidance for information regarding different levels of risk and types of IRB Review.

Examples Not Requiring IRB Review

  • CLASS PROJECTS involving secondary data analyses that are assigned and conducted as educational exercises, using data that are either publicly available data, de-identified or otherwise impossible to be linked to personal identities.
  • CLASS PROJECTS involving secondary data analyses that are assigned and conducted as educational exercises, and that use datasets that include private information and codes that link to identifiers, but the students do not have access to the identifiers.
  • CLASS PROJECTS or PRACTICA that involve direct interaction (e.g., in person, via mail, email, web surveys, or telephone), but where the purpose is training, an educational exercise or professional development, and not considered research by Federal definition. The project or practicum is not “research” even if students ask people questions as part of learning how to conduct interviews or surveys, take histories, administer assessments, or perform “in-house” evaluations as requested by the practicum site.

Examples Requiring IRB Review

  • If a student decides after the completion of a practicum activity to pursue additional activities with the same information for a master’s project or paper, then an IRB application describing research use of secondary data should be submitted for approval, as above.
  • CLASS PROJECTS or PRACTICA that involve direct interaction or secondary analyses of private identifiable data and are undertaken as both an educational experience and as research (e.g., results of these activities will be presented publicly or otherwise disseminated, or the data will be stored and used by the students or others as research data).

Responsibility of Course Instructors

The instructor/faculty must complete the required CITI human subjects in research training.

To ensure ethical conduct of student class projects, instructors who assign a class project are expected to review student plans prior to subject recruitment and data collection.

When a student project does require IRB review, the Instructor must comply with the responsibilities as listed under Investigator Responsibilities, as well as additional mentoring responsibilities as listed below:

1. Review each student project prior to submission to the IRB for accuracy and completeness.

2. Assist and support the student in his/her interaction with the IRB and oversee resolution of issues that arise during the review process.

3. Oversee of the student’s research to ensure that human subjects are protected, e.g., the protocol is followed as approved, any unanticipated events are reported as required, etc.

4. Verify that prior approval of Thesis or Dissertation Committee, if applicable, has been obtained.

Responsibility of Students

Student researchers have responsibilities as listed under Investigator Responsibilities.

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8. Types of Research

Types of Research Notes
Applied Scientific investigations conducted to answer specific clinical questions or solve practice-related problems.
Basic Scientific investigation that involves the generation of new knowledge or development of new theories; its results often cannot be applied directly to specific clinical situations.
Correlational The systematic investigation of relationships among two or more variables, without necessarily determining cause and effect.
Descriptive Research that provides an accurate portrayal of characteristics of a particular individual, situation, or group.  These studies are a means of discovering new meaning, describing what exists, determining the frequency with which something occurs, and categorizing information.
Ethnographic The investigation of a culture through an in-depth study of the members of the culture; it involves the systematic collection, description, and analysis of data for development of theories of cultural behavior.
Experimental Objective, systematic, controlled investigation for the purpose of predicting and controlling phenomena and examine probability and causality among selected variables.
Exploratory Studies that are merely formative, for the purpose of gaining new insights, discovering new ideas, and increasing knowledge of phenomena.
Grounded Theory A research approach designed to discover what problems exist in a given social environment and how the persons involved handle them; it involves formulation, testing, and reformulation of propositions until a theory is developed.
Historical Research involving analysis of events that occurred in the remote or recent past.
Phenomenological An inductive, description research approach developed from phenomenological philosophy; its aim is to describe an experience as it is actually lived by the person.
Qualitative Research dealing with phenomena that are difficult or impossible to quantify mathematically, such as beliefs, meanings, attributes and symbols.
Quantitative Research involving formal, objective information about the world, with mathematical quantification; it can be used to describe test relationships and to examine cause and effect relationships.

Note: The practice of telephone screening and consent for potential subjects is considered research and could occur in any of the above types of research.

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8.1 Standard Clinical Trial Protocol

A complete protocol is required for Committee review. Researchers who are participating in a multi-center protocol may submit the lead investigator/sponsor’s protocol. The Committee requires that the “Human Research Protocol” form be utilized any time a local researcher is writing his/her own protocol, or when a grant is being submitted for review. This form includes all of the elements as listed below in a format that is easy to complete and easy for Committee members to review. The form can be found on our forms page.

The “Qualitative Research Protocol Form” should be used instead of the “Human Research Protocol” form when submitting qualitative research or primarily qualitative research and when medical procedures are not included in your research. See the section on Qualitative Research Protocol for more information.

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8.1.1 Elements Found in a Standard Protocol

The following elements, when applicable, should be included in your protocol. The Committee may request that additional sections be added to a protocol to address additional protections for certain categories of human subjects when applicable.

Title Page

A title page should include the title of the project, number of project if applicable, and the Principal Investigator’s address, e-mail, and phone numbers. Include any of the following names and contact information if applicable: sub-investigators, statistician and research coordinator (not a required element).

Table of Contents (not a required element)

Introduction

The importance of the research and the potential knowledge to be gained should be explained in detail. Give background information, including references to prior human or animal research and references that are relevant to the design and conduct of the study.

Objectives

Clearly state the primary objective(s) of the study.

Study Design

Describe the research design and the procedures to be used to accomplish the specific aims of the project. Include how the data will be collected, analyzed, and interpreted as well as the data sharing plan as appropriate. Describe any new methodology and its advantage over existing methodologies. Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the objectives. As part of this section, provide a tentative sequence or timetable for the project. Point out any procedures, situations, or materials that may be hazardous to personnel and the precautions to be exercised.

Inclusion/Exclusion Criteria

Eligibility and ineligibility criteria should be specific. Changes to the eligibility criteria at a later phase of the research have the potential to invalidate the research.

Methods

Describe the types, frequency and duration of tests, study visits, interviews, questionnaires, etc. Include required screening procedures performed before enrollment and while on study.

Withdrawal Procedures

Define the precise criteria for withdrawing subjects from the study. Also include a description of study requirements for when a subject withdraws him or herself from the study (if applicable).

Statistical Considerations

Delineate the precise outcomes to be measured and analyzed. Describe how these results will be measured and statistically analyzed. Delineate methods used to estimate the required number of subjects. Describe power calculations if the study involves comparisons. Perform this analysis on each of the primary and secondary endpoints, if possible.

Human Subject Protections:

Subject Selection: Provide rationale for subject selection in terms of the scientific objectives and proposed study design.

Include as appropriate:

Inclusion of Minorities and Women: Describe efforts to include minorities and women. If either minorities or women are excluded, include a justification for the exclusion.

For protocols including the use of an investigational drug, indicate whether women of childbearing potential have been included and, if not, include appropriate justification.

If HIV testing is included specifically for research purposes explain how the test results will be protected against unauthorized disclosure. Include if the subjects are to be informed of the test results. If yes, include the process and provision for counseling. If no, a rationale for not informing the subjects should be included.

Special Populations: Explain the rationale for involvement of special classes of subjects, if any. Discuss what procedures or practices will be used in the protocol to minimize their susceptibility to undue influences and unnecessary risk (physical, psychological, etc.). See section: Additional Protections for Special Populations

Inclusion of Children: Describe efforts to include children. Inclusion is required unless a clear and compelling rationale shows that inclusion is inappropriate with respect to the health of the subjects or that inclusion is inappropriate for the purpose of the study. If children are included, the description of the plan should include a rationale for selecting or excluding a specific age range of children. When included, the plan must also describe the expertise of the investigative team in working with children, the appropriateness of the available facilities to accommodate children, and the inclusion of a sufficient number of children to contribute to a meaningful analysis relative to the purpose of the study. If children are excluded then provide appropriate justification. Provide target accrual for this population. See section: Children

Plans for Recruitment/Screening/Retention

All methods for subject recruitment, screening and retention need to be reviewed by the IRB. This review ensures respect for persons and their privacy, equitable selection, that the plans and information accurately portray the protocol, and that the method is free from coercion.

Allowable Recruitment Strategies

Study investigators who are health care providers (clinicians) providing direct care can recruit their own patients

The process needs IRB approval prior to use. Any UVM Medical Center clinician, his/her immediate practice group, or nurses/staff working with those clinicians may approach a patient for research participation.

Study investigators with no treatment relationship may send a “Dear Doctor” letter asking for referrals of eligible patients who are interested in research participation

The referral letter and the process needs IRB approval prior to use. This recruitment strategy requires that the potentially interested patient contact the researcher as the study investigator has no relationship to the patient. The study investigators are prohibited from having access to patient names, addresses or phone numbers; patients must initiate contact.

Study investigators with no treatment relationship may provide their colleagues with a “Dear Patient” letter describing the study.

The “Dear Patient” letter and process needs IRB approval prior to use. A PI may send a letter to clinicians requesting that they address and send a “Dear Patient” letter describing the research study to potentially eligible patients. This letter is signed by the treating clinician and provides the patients with contact information for the study investigators. The study investigators are prohibited from having access to patient names, addresses or phone numbers; patients must initiate contact.

Study investigators with no treatment relationship who are collaborating with the treating clinician may send a collaborative “Dear Patient” letter describing the study.

The “Dear Patient” letter and the process needs IRB approval prior to use. In the event that the research is a collaborative effort between the treating clinician and the study investigators, a joint letter, signed by both, introducing the study investigator as a collaborator along with a description of the study may be acceptable. This letter would inform potential patients that there is an established relationship between their treating clinician and the study investigator.

The preference would be that the interested patient contact the researcher, however in this instance, given that a relationship between their treating clinician and the study investigator has been communicated to the patient, the investigator may contact the patient. A script of the phone contact by the study investigator will be required for review.

Study investigators with no treatment relationship recruiting patients (inpatient or outpatient)

An investigator may only approach a patient about participation in a research study after permission from the patient to be approached has been documented by the treating clinician, preferably in the medical record. Study investigators may provide the treating clinicians a study information sheet to be given to the patients.

A partial waiver for recruitment will be necessary if the investigator wishes access to medical records to screen for eligible patients.

Study investigators recruiting potential subjects who are unknown to them for behavioral or non-clinical research

Examples include snowball sampling (existing study subjects recruit future subjects from among their acquaintances), use of social networks, direct approach to unknown people in public situations, and random dialing.

UVM Psychology Participant Pool is an approved mechanism to facilitate undergraduate student participation in research for either required course credit or optional course extra credit. For more information regarding this method of recruitment, contact the Psychology department.

Advertisements

All recruitment materials including recruitment letters, posters, newspaper ads, radio spots, TV commercials or public service announcements are to be forwarded to the IRB for review and approval prior to use. Generally, advertisements used to recruit research subjects should be limited to information that a potential subject would need to determine if they are eligible and interested in participating. More specifically, the ads should include information such as:

a. Name and address of the research facility;

b. The condition or disease that will be the focus of the research;

c. A clear statement that the study is research; (required)

d. Summary of criteria for eligibility to participate;

e. Time and commitments that will be required of the subject;

f. Location of the study and the contact for information.

The ads should not:

a. Contain explicit or implicit claims of safety and efficacy or equivalency or superiority to other approved treatments;

b. Emphasize the amount of reimbursement that subjects will receive. The ads may state that reimbursement may be provided;

For example, posters in which the compensation amounts are too large or are too prominently presented (i.e. bold typeface or large fonts) will not be approved;

c. Promise a favorable outcome or benefit.

Recruitment materials should be placed in areas which allow for equitable recruitment of subjects. You need to indicate where the material will be placed.

For example, if a researcher advertises in the classified section of the newspaper, the personal column or a “block ad” is considered most appropriate. These should never be placed in the “employment section” of any type of media, (e.g. newspaper or Craig’s list). Particular attention should be paid to emphasize the “volunteer” and “research” aspects associated with participation.

If recruitment is media-based, provide script, if available, and what stations will air it.

If there is a national campaign, provide the press release as soon as it is available and list which stations will air the release.

Recruitment mailings to subjects’ should be stamped confidential or personal. We recommend the use of window envelopes to avoid errors in mailing.

Phone recruitment scripts need to be submitted for review and approval. Conversation with parties other than the subject you are trying to contact should not reveal the purpose of the call. Phone mail messages revealing the purpose of the call should be avoided.

It should be carefully explained to a potential subject that voluntary participation in a research project does not constitute employment.

Direct Mail Recruitment

Direct mail campaigns obtain subjects’ names and contact information through large marketing firms who have conducted voluntary surveys of U.S. households. The collected information and consent of the survey volunteer to receive information are placed in a database. This information is then used by direct mail vendors to alert these individuals of new offers or information pertaining to their selected responses.

Details about the mail campaign and the proposed letter and/or materials must be reviewed and approved by the Committee prior to vendor distribution. The letter and/or materials must contain local information such as PI, address, and a telephone number for the subjects to contact. There should also be mention of the how the subjects’ contact information was obtained for the mail campaign.

Direct E-Mail Recruitment

Use of a company or university list-serve for recruitment purposes must be approved by the institution that manages/owns that list-serve. The IRB will request proof that permission has been granted by the institution.

Students and Employees

Though the research may be careful to avoid potentially coercive behavior, the very nature of the relationship with the subject can create the appearance of coercion. Even subtle cues of compromise can place subjects in a position of involuntary participation in a research project. For this reason, researchers should be aware of the potential for coercion that exists when a research subject is also a student, employee, colleague, or subordinate of the researcher.

Various procedures have been suggested to reduce the possibility of unintended coercion, while still permitting their participation as subjects in research. These include:

  • Posting IRB approved advertisements/posters throughout the university to recruit subjects from a broad base;
  • Avoiding any personal solicitations of students by faculty, graduate assistants, or fellow students. In seeking potential subjects among employees, the best strategy is to utilize a third party unassociated with the work relationship;
  • Providing a number of research projects from which to choose, if participating as a subject is a course requirement;
  • Providing alternative and equal methods for meeting course credit (or extra credit) requirements, such as attending a series of research presentations by faculty, writing a brief paper, conducting one’s own research;
  • Making it clear in the consent form that refusal to participate will not affect class standing, grades, status on an athletic team, or job standing.

It is IRB practice not to approve recruitment procedures that include employees from the investigator’s own lab or office, especially when the procedures are more than minimal risk. The IRB, however, may reconsider this practice on a case-by-case basis.

Investigator Self-Experimentation

Some researchers may want to participate in their own studies, a practice known as “self-experimentation.” The federal regulations are silent on this point, making no distinction between self-experimentation and participation by others. The IRB requires that such self-experimentation be fully described in a protocol that is submitted for IRB review.

This policy (1) may protect researchers from unwarranted risks and (2) allows a neutral third party to raise concerns, if any, regarding credibility of resulting data.

Note: There is a difference between being a participant in the research and research development/evaluation or testing designed to validate tools for the research project. If the investigator is involved in development only, this would not be considered research and therefore a research study consent form does not apply. However, if any of the procedures involves more than minimal risk, a consent or acknowledgement of understanding should be conducted and documented within the research files.

A main concern for the IRB when reviewing a protocol that involves self-experimentation, is that the ideation of a novel concept may outweigh the investigator’s concern for his/her own welfare.

The IRB may institute additional safeguards for the research project, such as shorter review periods, monthly progress reports, or require that an IRB member obtain informed consent from the investigator.

Screening Options

Review of patient medical record to determine eligibility

Researchers who have a treating relationship may have access to their patient files to determine eligibility without prior IRB approval. When the researcher does not have a treatment relationship with the subject, prior IRB review and approval of the planned recruitment procedures is necessary. Researchers wishing to access protected health information for the purpose of establishing suitability for subject inclusion may wish to request a partial waiver of the HIPAA authorization requirement. This partial waiver allows access to the information that is needed for the recruitment, but does not allow the researcher to take the information from the medical record. Complete “Request for Partial Waiver of Authorization for Recruitment Purposes” form if you wish to waive authorization to review information

Further IRB review and approval would be necessary to allow removal of information or to further contact potential patients. Please refer to section 10.1 for additional HIPAA information.

Screening in the Emergency Department

The Emergency Medicine Research Associate Program (Surgery Class 201) is an undergraduate class of students who are being trained in research methods and are available to assist researchers with screening for patients in the Emergency Department. These students do not approach or consent patients. For more information regarding this resource, contact the director of the program.

Telephone Screening for Eligibility

The practice of telephone screening to establish eligibility is an allowed process. If patients are the population, only those study investigators who are also the treating clinicians or study investigators who have an established relationship to the subject can contact the patient by telephone. The telephone screen is part of the research project and because investigators are not able to obtain written consent to the phone screen, the investigator must submit a waiver of documentation of consent and a telephone script for review.

Subject Retention

It is understood that many studies require long-term follow up for disease and survival data. The protocol should account for this follow up from the outset and subjects should be made aware of this requirement at the time of consent to participate.

The Committee generally discourages use of subject locator services. Contact by a service rather than the treating physician/researcher may be potentially upsetting to the subject and subjects appear to lose their right to privacy when a service, unbeknownst to them, is using different methods to locate them. Requests for use of a locator service are considered on a case-by-case basis and will only be approved if the methods are appropriate and the need for finding a subject is justified.

Any items such as money, small tokens, gift certificates, etc, which are given to the subject to retain their participation in research is considered a form of compensation and needs prior approval by the IRB.

Subject Compensation

Compensation may be in the form of money, course points, travel expenses, gift cards, etc. The compensation for participation in the research will be reviewed on a protocol-by-protocol basis. The amount should be commensurate with what is being asked of the participants and can not be considered coercive. Compensation should not be dependent upon completion of the protocol and there should be a proration schedule. Participation cannot be required for academic course credit or course completion. Researchers should consider how compensation could impact participant’s state or federal benefits (i.e., SSI, SSDI) eligibility in their consideration of compensation type and amount.

Compensation Guidance when Minors are Involved

The level of risk to which a child is exposed is an important consideration for the IRB in determining the appropriateness of payment. The IRB shall ensure that the amount, type, and timing of payment does not unduly pressure or influence the decision making of parents or legal guardians to enroll their child in the research activity.

In pediatric research, inducements are generally tailored to the child participant. Inducements may also be made to the parents or legal guardians of children taking part in research. For example, researchers may provide a payment that represents partial compensation to parents for their time away from work for example when a research study visit requires a full day of the parent's time to accompany their child for a research visit.

Inducements to children shall be age appropriate and respectful and sensitive to children and families. Researchers providing inducements to children shall be encouraged to have several options available for children and families that allow children and families to choose an inducement that is consistent with the family's values. The IRB encourages non-cash payments, e.g., gift cards/certificates, movie/event tickets, toys, books, as forms of payment that are respectful to children and reduce the potential for unduly influencing the child's legal representative's decision regarding participation.

Compensation from UVM Funds

Research subjects who are eligible for compensation through UVM are required to provide personal information such as name, address and social security number in order that they are paid. In addition to cash, this includes gifts, tokens and gift certificates. The social security number is only needed if a single payment is more than $100.00. If the total sum of payments within one year are expected to be greater than $600.00, the social security number is required at the time of their first visit only. See UVM’s Procurement site for additional information and detail about processing subject payments.

Compensation from UVM Medical Center

Research subjects who are eligible for reimbursement from the research study through UVM Medical Center have to provide their social security number at the first visit regardless of the amount of payment. UVM Medical Center assigns a unique ID upon the first payment visit and uses that ID going forward to reimburse subjects.

In both cases all correspondence should be sealed in an envelope and marked confidential.

Note: Principal Investigators are not allowed to use their own personal funds to compensate participants.

Risks/Benefits

Describe any potential risks. This includes physical, psychological, social, legal or other risks. Describe the planned procedures for protecting against or minimizing potential risks and assess their likely effectiveness. Where appropriate, discuss plans for ensuring necessary medical or professional intervention in the event of adverse effects to the subjects. Discuss the potential benefits of the research to the subjects and others. Discuss why the risks to the subjects are reasonable in relation to the anticipated benefits to subjects and others. Discuss the importance of the knowledge gained or to be gained as a result of the proposed research and why the risks are reasonable in relation to the knowledge that reasonably may result.

NOTE: If the study involves the collection, storage or analysis of genetic information, the Genetic Information Nondiscrimination Act (GINA) is invoked. GINA language must be included in the subject consent form. Language can be found in the IRB consent template located on our forms page.

Confidentiality

Provide a statement describing the extent to which confidentiality of materials (data and specimens) identifying the subject will be maintained and that notes the possibility that the Institutional Review Board and regulatory authorities may inspect the materials.

Data Safety and Monitoring

The specific design of a Data and Safety Monitoring Plan (DSMP) for a protocol may vary extensively depending on the potential risks, size, and complexity of the research study. For a minimal risk study, a DSMP could be as simple as a description of the Principal Investigator’s plan for monitoring the data and performance of safety reviews or it could be as complex as the initiation of an external, independent Data Safety and Monitoring Board (DSMB).

The data and safety monitoring plan should provide for a regular review of accrued research data and other relevant information to ensure the validity and integrity of the data and that there is no change to the anticipated benefit-to-risk ratio of study participation. In addition, there should be an ongoing review of study procedures to ensure that the privacy of research subjects and the confidentiality of research data has not been violated.

The following general principles should be considered when addressing an appropriate data and safety monitoring plan:

Protocols with interventions require some level of monitoring;

Monitoring should be commensurate with risks;

Monitoring should be commensurate with the size and complexity of the study;

Monitoring should be performed on a regular basis;

Conclusions of monitoring should be reported to the appropriate individuals/groups.

Specific monitoring requirements may be necessary for the following: NIH grant applications for Phase I/II/III clinical trials; Clinical Research Center protocols; University of Vermont Cancer Center protocols; NCI-funded clinical trials; gene therapy trials; or multi-center trials when UVM is the lead institution.

A Data Safety and Monitoring Board (DSMB) is an external, independent committee of scientists, physicians, statisticians, and others that collects and analyzes data during the course of a study to monitor for adverse effects and other trends (such as an indication that one treatment is significantly better than another, particularly when one arm of the study involves a placebo control) that would warrant modification or termination of the study or notification to study participants about new information that might affect their willingness to continue in the study. Typically, protocols that are industry sponsored accrue multiple subjects at multiple sites and are required to have the appropriate resources to capture and report issues of safety and do this by means of a board or equivalent.

Unanticipated Problems to Subjects and Others Reporting

All protocols should specify that, in the absence of more stringent reporting requirements, the guidelines established in the Committees on Human Research “Unanticipated Problems Reporting Policy and Procedures” will be followed. The UVM/UVM Medical Center requirements for reporting adverse events and unanticipated problems to subjects and others should be included in the DSMP. For research protocols utilizing the UVM 3T research magnet, you must have a plan for handling incidental findings. Refer to guidance on incidental findings, see Incidental Findings in Neuroimaging Protocols – Detection and Management policy.

For protocols using the CRC, additional adverse event reporting mechanisms exist. The CRC Office of Research Subject Advocacy is available to assist you in meeting these requirements. Please call the RSA Office (847-0433) or visit the CRC website for sample language on this topic to include in your protocols.

Sources of Materials

Identify sources of research material obtained from individually identifiable human subjects in the form of specimens, records or data. Indicate whether the material or data will be obtained specifically for research purposes or whether use will be made of existing specimens, records or data.

Collaborating Sites

When research involving human subjects will take place at collaborating sites or other performance sites when UVM/UVM Medical Center is the lead site, the principal investigator must provide in this section a list of the collaborating sites and their Federalwide Assurance numbers when applicable. Sites added after initial approval must be submitted as an amendment to the IRB and must adhere to the same requirements. Additional agreements may be required, see the Multi-institutional Research Policy.

Consent and HIPAA Authorization

The consent form with incorporated HIPAA authorization language (if protected health information (PHI) is included, (see sections on Consent and HIPAA for further information about PHI)) should accompany the protocol as an appendix or attachment.

References

Include references.

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8.1.2 Requirement to include a full Protocol Title in the Electronic Medical Record (EPIC)

UVMMC requires that certain information (full protocol title, CHRMS/CHRBSS protocol number, Principal Investigator and Principal Investigator’s contact information) about research study participation be included in the Research Flag area of each participant’s electronic medical record. This requirement is for participant safety and billing compliance.

It is expected that full protocol titles are included in EPIC, however it is recognized that there may be rare circumstances in which inclusion of the full study title is inappropriate.

If the Principal Investigator feels that including the full protocol title in the EPIC record is not in the best interest of the participant, they may request a waiver of this requirement. The waiver request will either be that the protocol title is withheld completely (EPIC will indicate “Protocol title withheld due to the confidential nature of the research”), or that an alternate title, proposed by the Principal Investigator, is substituted.

Examples of appropriate justification to waive the requirement to include the full protocol title or alter the title:

  • There is more than negligible risk of stigmatization or discrimination by health care providers, health insurance plans, employers, or others by placing the protocol title in the medical records of participants.
  • There is an expected deterrent effect on research participation by including the protocol title in the medical records of the study population.
  • There is misleading information (for example disease condition, drug names) that might lead to conclusions about the person’s condition or related treatment which may increase potential for risk to the participant.

Example of inadequate justification to waive the requirement to include the full protocol title or alter the title:

  • Participant privacy by itself is not considered an appropriate justification as electronic medical records are considered private. All personnel with access to the Research Flag in EPIC have completed training in confidentiality and privacy matters and the appropriate access and use of patient medical information. In addition, UVM Medical Center tracks all EPIC access and audit trails are in place to monitor access.

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8.2 Chart Review Protocol

The Committee receives many projects where the only procedure is gathering health information (e.g., data mining, chart review, pathology slides or radiographic reviews). If your project includes any additional procedures, this form would not be appropriate.

Any project that requires access to protected health information from a covered entity is required to undergo an expedited review. The covered enitities are UVMMC and UVM Eleanor M. Luse Center. We have combined the necessary data points from each of our submission forms into one form for the Committee to conduct this review. This form may be found on the IRB forms page of our website.

Please note that if you are utilizing the Jeffords Institute for Quality, you must obtain approval from them prior to sending to the IRB for review.

Chart refers to medical records, electronic or paper, pathological specimens or diagnostic specimens, or any other type of existing record (e.g. educational record, criminal records, etc.)

  • A retrospective chart review evaluates data that is existing at the time the project is submitted to the IRB for initial review.
  • A prospective chart review will evaluate data that does not yet exist at the time the project is submitted to the IRB for initial review.

Categories of IRB Review

  • Exemption Category 4: Research involving the collection or study of existing data, documents, records, pathological specimens or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
    • All data/material must be in existence at the time of IRB submission.
    • No identifiers or links can be recorded. Your study will not qualify for exemption if you intend on recording any of the following identifiers:
18 Identifiers

1. Names

2. All geographic subdivisions smaller than a state*

3. Telephone numbers

4. Fax numbers

5. Electronic mail addresses

6. Social Security numbers

7. Medical record numbers

8. Health plan beneficiary numbers

9. Account numbers

10. Certificate/license numbers

11. Vehicle identifiers and serial numbers, including license plate numbers

12. Device identifiers and serial numbers

13. Web Universal Resource Locators (URLs)

14. Internet Protocol (IP) address numbers

15. Biometric identifiers, including finger and voice prints

16. Full face photographic images and any comparable images

17. All elements of dates (except year)**

18. Any other unique identifying number, characteristic or code

*including street address, city, county, precinct, zip code, and their equivalent geocodes, except for the initial three digits of a zip code, if according to the current publicly available data from the Bureau of the Census: (1) The geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and (2) The initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000.

**for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older.

If this study involves chart review of Prisoners it must be submitted for a full board review.

Exemption Category 4 Addressing Informed Consent and HIPAA Authorization

  • Waiver of Consent is applicable
  • HIPAA is not applicable if there is no protected health information (PHI)
  • When PHI is included, de-identified PHI is exempt from HIPAA requirements as long as a certification of de-identification is in place. Certification means that even though researchers are seeing identifying information during chart review data extraction, the researchers will NOT record any identifying information. The only methods by which data may be classified as de-identified are
  • by certifying that none of the 18 HIPAA-defined identifiers are used, reviewed, or recorded by the research staff
  • by certifying that as a member of our covered entity the individual using PHI to create a de-identified data set
    • keeps all information seen in the process of creating the de-identified data strictly confidential
    • does not record any of the identifiers defined by HIPAA
    • cannot link the data back to the individual in any way, or
  • by certifying through statistical analysis on each identifier that is contained within the data that the likelihood of an individual being identified by using the data in whole or part is very small. Statistical de-identification must be done by a qualified statistician and the methods and results of the analysis must be documented.

When protected health information is being accessed, researchers will be required to complete the Certification of De-Identification section of the exemption form. This area must be signed by the PI and all person(s) who will be extracting data from charts.

  • Expedited Category 5: Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected, solely for non-research purposes (such as medical treatment or diagnosis).
  • Allows for the prospective collection of data that is later reviewed for research purposes.
  • Identifiers and/or links can be recorded if necessary.

If this study involves chart review of Prisoners it must be submitted for a full board review.

Expedited Category 5 Addressing Informed Consent and HIPAA Authorization

  • Obtaining consent must be addressed, whether you are requesting a waiver of the entire consent process, obtaining written consent, or requesting a waiver of documentation of consent.
  • Obtaining HIPAA must be addressed when identifiers are retained. The HIPAA-approved language must be included within the consent form.
  • Waiver or alteration of HIPAA authorization may be requested in certain circumstances. The principal investigator must submit a request for waiver of authorization to the IRB for review and approval. To approve the waiver the following elements must be satisfied:
  • The use and/disclosure of the PHI involves not more than a minimal risk to the privacy of individuals;
  • The research could not practicably be conducted without the waiver; and
  • The research could not practicably be conducted without access to and the use of the PHI.

To request a waiver or alteration of the requirement for a HIPAA authorization, complete and submit the form titled “Request for Waiver of Informed Consent/Authorization/Documentation (DOCX)”.

Secondary Research - Health Records Review Projects (New section! Do not reference until the 2018 revised Common Rule takes effect)

The Committee receives many projects where the only procedure involves gathering secondary health information (e.g., data mining, chart review, pathology slides or radiographic reviews) for research. If your project includes any additional procedures, health record review is not appropriate.

IRB Review

If identifiable private information or identifiable specimens are publically available, the project can be exempted under Exemption Category 4.

If the information or biospecimens are recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects, the project can be exempted under Exemption Category 4. Note: Certification of De-Identification of information will be required.

If the project involves use of identifiable health information from a covered entity, the project must be reviewed through a limited (expedited) review process to determine whether the project meets Exemption Category 4. If it does not meet Exemption Category 4, Expedited Category 5 will be employed. The only difference between the two determinations is that a determination under Expedited 5 requires that an annual update be submitted to the IRB.

Source of Records

Health records refers to medical records, electronic or paper, pathological specimens or diagnostic specimens, or any other type of existing record (e.g. educational record, criminal records, etc.) The covered entities are UVMMC and UVM Eleanor M. Luse Center.

Please note that if you are utilizing the Jeffords Institute for Quality, you must obtain approval from them prior to sending to the IRB for review.

Retrospective versus Prospective Health Records

2018 Common Rule now allows for Exemption 4 determination whether the data is retrospective or prospective.

  • A retrospective chart review evaluates data that is existing at the time the project is submitted to the IRB for initial review.
  • A prospective chart review will evaluate data that does not yet exist at the time the project is submitted to the IRB for initial review.

 

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8.3 Qualitative Research Protocol

The “Qualitative Research Protocol Form” should be used instead of the “Human Research Protocol” form when submitting qualitative research or primarily qualitative research and when medical procedures are not included in your research.

Qualitative Research Protocol

The Qualitative Research Protocol form SHOULD be used for proposals where the significant majority of the research methods are qualitative. It SHOULD NOT be used for studies involving human specimens or medical procedures even if the study is primarily qualitative because of the additional regulatory requirements for human subject protection.

Proposals that primarily are composed of qualitative methods, e.g., research “in the field,” phenomenological or ethnographic research proposals may not fit a traditional research design or IRB review model. Still, from the standpoint of federal regulations and professional ethical codes in the social sciences, the same principles and guidelines for protection of the rights and welfare of subjects/participants apply. The IRB has developed a specific “Qualitative Research” protocol form to assist with member review.

You must accurately determine if what you are proposing is qualitative research. Qualitative research is the gathering of data primarily through the methods of participant observation, observation, face-to-face interviews, or open-ended surveys or questionnaires, often for the purpose of addressing questions pertaining to social and/or cultural issues. There are several kinds of qualitative research, such as ethnography, historical, field research, phenomenological, grounded theory, and case studies. Such research may describe a social situation as a whole, or it may focus on specific problems or situations within a larger social context.

Quantitative research generates numerical data or information that can be converted into numbers.

Medical research means direct medical intervention or interaction, clinical trials for new drugs/devices, FDA regulated activities, invasive or non-invasive medical procedures for research purposes or the collection or use of private health information for research purposes in the biomedical arena.

Sometimes research protocols combine both qualitative and quantitative research methods, referred to as mixed-method research. If you are doing mixed methods research with equal parts qualitative and quantitative methodology, you will need to choose the submission form that best describes your research to someone outside of the study team (i.e. for IRB staff and Committee Members to review).

The IRB appreciates that qualitative research has the following special characteristics (Arwood, T., and McGough, H., 2007 PRIM&R SBER Conference):

  • It is experiential
  • It is interactive
  • It is not easily bounded by time and place
  • It is often exploratory
  • It morphs easily and often (new questions emerge during research)
  • The boundaries between normal activities and communication and data collection are blurred

In order for the IRB to understand these special characteristics and the nature and scope of a particular qualitative research project, the following issues should be addressed in the Qualitative Research Protocol, if applicable.

Participant Population

  • The kinds of people who will be involved in the research should be described. If there are different groups or categories of people, the groups and the approximate number of participants in each group anticipated to be enrolled must be described. If potentially vulnerable populations are included, any additional protections should be explained. If an exact number of people to be enrolled are unknown, a range should be provided. An amendment should be submitted to the IRB when/if actual numbers exceed those estimates.

Description of Procedures

  • The length of time to be spent at the field site(s) should be described. If unsure, an approximate length of time should be provided (e.g., one year, two summer months, etc.). Also the approximate length of time of the interaction with subjects (i.e. 2 hour interviews, day-long observation) and the number of anticipated interactions (i.e. 3 interviews over a 4 month period) should be provided. An amendment should be submitted to the IRB when/if actual dates exceed those estimates.
  • The research techniques that will be used to conduct the research (such as participant observation, interviews, focus groups, use of public, private governmental or other records, administration of test, etc.) should be described. The topics or research domains to be covered as well as what will be observed (such as individual behaviors, community rituals, societal norms, etc.) should be described. This will help the IRB get a sense of what will be learned from and about the participants in the research.
  • Explain how the maximum number of participants is determined or what criteria will be used to determine when data collection is completed.

Research Site(s) or Location(s)

  • Explain where the research will be conducted and explain why this particular research setting was chosen.
  • Has the researcher conducted research at this site or with the population previously? If so, briefly describe the topics and duration of your previous research.
  • Is local governmental or community permission to conduct research required at any of the sites? If so, explain how you will obtain this permission. If there is formal documentation of this permission, attach it to the application form or indicate when it will be received and forward to the IRB.
  • Will you work with local collaborators (interviewers, interpreters, translators, guides, etc.)? If so, please explain who these collaborators are and how they will be involved in the research. Will they need to obtain local ethics committee approval for their role in the study?
  • Many countries have the expectation that foreign scholars will collaborate with local scholars and institutions. Explain whether this applies to your research and if local IRB or other type of ethical review board approval will be obtained.

Risks and Inconveniences

Risk of harm in qualitative research is usually limited to what may result from invasion of privacy, stigmatization, or breach of confidentiality. Harm may happen to individuals and to the groups or communities to which they belong.

  • Identify the risks of harm that may result from this research.
  • Describe the steps you will take to minimize the risks of harm. If harm occurs, what plans do you have to manage it?
  • If there are different risks of harm for different groups of participants, please identify the risks for each group. Sometimes this cannot be known in advance of entering the field. If unanticipated problems occurrence research has begun, the incidents must be reported to the IRB. When appropriate, the study can be modified to address any issues that arise.

Benefits

  • Is it possible that individuals who take part in your research can reliably expect a direct benefit from taking part? If yes, describe.
  • Describe the anticipated benefits of this research for the community you will study, for your profession, or for society in general.

Confidentiality

  • Describe how you will find out how people in this setting feel about the fact that you will write articles about them. Will you consult with the people from whom you collected data before you publish?
  • Are any portions of the research material you may collect not publicly available and expected by community standards to be private? If yes, describe the materials that are private and explain (1) how you will store the private information or materials while you are in the field so that the confidentiality of the data is protected; (2) explain how you will store the private information or materials after you leave the field so that confidentiality is protected; (3) explain whether you will retain information that could lead to identification of the research site and explain any negative consequences this could have; (4) explain if you will record any direct participant identifiers (such as names or contact information) that could be linked to the private research material.
  • If you will record identifiers (# 4 above) explain why and describe how you will protect against disclosure of this information or explain why this is not necessary. If you will retain the identifiers linked to the data, explain (1) how long the identifiers will be kept, (2) how confidentiality will be maintained during this period, (3) who will have access to data (such as sponsors, advisors, government agencies, etc.). In each case, explain whether they will have access to study data with identifiers or only to coded data with no access to the identifying study code. If identifiers will be maintained indefinitely, explain why. For example, do you intend to re-contact participants or communicate with them over a long period of time, or is the data identifiable by its nature (recordings, genealogies, etc.). Explain how you will protect the data from a breach of confidentiality or why this is not necessary.
  • If you will retain data that may place participants at risk for criminal or civil liability or be damaging to their financial standing, employability or reputation, please explain. It may be advisable to obtain a federal Certificate of Confidentiality.
  • The IRB acknowledges that sometimes it is not possible or desirable to maintain anonymity. For example, when a researcher works with a small group of people only found in a particular region with whom others have worked. In order to advance ethnographic knowledge about the group, their identity must be made known.

Sometimes individuals or whole communities do not want to remain anonymous. If this is the case, explain how you learned of this and describe why. If there are differences in the community about this, describe how this will be handled.

Consent Procedures/Process

  • Explain how you will introduce yourself as a researcher to potential participants. If you already know them, please explain the circumstances.
  • How will you inform people about your research and obtain their consent to participate? If you plan to use an oral consent process and to work informed consent procedures into your introduction to a group, or the beginning of an interview, please provide a general script or a list of points you will cover.
  • Describe how people in this setting let you know if they don’t want to talk with you.
  • Identify who is responsible for giving consent in the research setting (for instance, if a tribal council or community leader provides consent for the entire group). Sometimes the consent process can be multi-layered in community settings. Be sure to describe what the full process is in the setting in which the research will take place.
  • Describe how you will handle situations in which group consent is provided, but individuals to not want to participate and vice versa.

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8.4 Biological Specimens/Data Repository Protocols

There is a category of expedited protocols that include the collection of samples or data for future research. What follows is policy and guidance for repository protocols. We have developed a submission form “Biological Specimens/Data Repository Protocol” to address management of repository activities.

NOTE: If you intend to share research data sets with other colleagues, you must obtain local IRB approval as well as the colleague’s IRB approval. The IRB typically requests that all individual identifiers be stripped prior to release. Justification for maintaining identifiers, even if coded, will be required. Sharing data outside of our institutions may require that a data use agreement be obtained. UVM investigators should contact Sponsored Projects Administration at 656-3360 to speak with the Executive Director. UVMMC investigators should contact the Office for Clinical Trials Research at 847-8990.

Biological Specimens/Data Repository Policy

The use and control of human tissue and medical charts for research is governed and restricted by federal and state laws and local regulations to ensure human protection measures are adequate. In the past tissue registries, tissue banks, pathology archives, research waste materials, hospital and clinic charts, and other databases have often been accessible to medical researchers. Often this “tissue” material was acquired from human subjects (living persons and fetuses) for non-research purposes such as diagnosis, medical therapy, public health control, quality assurance and transfusion/transplantation therapy. Researchers were often permitted access to these materials without adequate human protection mechanisms in place. More recently, human protection standards on use of tissue material have become more stringent and less trivial based on newly identified issues such as medical/legal privacy acts, HIV status, genetic confidentiality issues, religious and ethical beliefs, fetal restrictions, and other issues. The days of free access to personal data and tissues by researchers without subject consent have passed.

Operation of a specimen/data repository is now subject to oversight by the committee. The committee will review and approve a protocol specifying the conditions under which sample collection occurs and then all subsequent requests to access the specimens or data for research purposes. This is done to ensure adequate provisions to protect the privacy of subjects and maintain the confidentiality of data.

Definitions

Human tissue and data repositories collect, store, and distribute human tissue materials and data for research purposes. Repository activities involve three components: (i) collection of the tissue samples or data; (ii) storage of the tissues samples or data; and (iii) future use of stored tissue or data.

Tissues include any cell tissue, fluid, or excreta from which measures of normal or pathologic human physiologic function can be obtained. The term, “tissue” includes, but is not limited to pathological specimens, diagnostic specimens, hair and nail clippings, deciduous and permanent teeth, dental plaque and calculus, sweat, uncannulated saliva, placenta removed at delivery, amniotic fluid, cerebrospinal fluid, genetic material, urine, blood and other bodily fluids.

Data includes any private medical or non-medical information obtained from the subject, informant or the medical chart.

Coded or De-Identified means that identifying information (HIPAA Identifiers List) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain, has been replaced with a number, letter, symbol, or combination thereof (i.e., the code); and a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

Protocol Requirements

The IRB has developed a “repository” protocol form and process that covers all the following requirements.

1. person responsible;

2. description of all tissue/data that will accumulate in the bank;

3. physical location and security measures of the bank;

4. a separate “repository consent form” or request for a waiver of consent/authorization;

5. pledge that the responsible party will not use or release tissue or data unless an IRB application is submitted for every proposed analysis of that data;

6. internal monitoring in place to cross check samples, data, consents and withdrawals;

7. safeguards against identification; use of a third party system;

8. process to evaluate tissue utilization;

9. length of time specimens or data are kept; how destroyed; and

10. what information will be shared with subject(s).

As is usual, the protocol should discuss these issues in enough detail for the IRB members to evaluate the plans; a somewhat briefer description should be included in the consent form.

OHRP strongly recommends that a Certificate of Confidentiality be obtained to protect confidentiality of human cell repository specimens and data.

Consent Form Requirements

The IRB has developed a standard specimen collection consent form which includes the following elements:

1. operation and security of the repository;

2. specific types of research to be conducted (as specific as possible with the basic idea to determine if there is any type of research to which the subject might object);

3. conditions under which data and specimens will be released to recipient-investigators;

(other site must have IRB approval);

4. procedures for protecting the privacy of subjects and maintaining the confidentiality of data;

5. sensitivity of the generated information (E.g. information that could affect a subjects employment, insurance coverage etc., (if DNA typing is involved include information on consequences (paternity));

6. non-exculpatory language through which subjects are made to waive or appear to waive any legal rights;

7. freedom to withdraw: how will confidentiality risk be terminated;

8. whether or not it is anticipated that the subject may be approached for follow-up information or follow-up samples in the future (a process to which the subject should have the opportunity to give or deny consent);

9. voluntariness of participation;

10. the degree to which ongoing access to medical records is being sought for correlative information, and the duration of such access; and

11. the kind of information that will be provided to subject(s).

Reporting Individual Results to Subjects

For general repository activities, it is probably best to plan not to provide results of future studies to the subjects. Much of the future research will be conducted without identifiers, and it is unlikely that most research will yield results that, if known, would affect the patients' health care or family planning. In fact, there are many cases in which it would be unethical to provide results to patients, such as when the research is in the early stages and the clinical significance has not been established. On the other hand, if there is a good chance that research will yield results that could affect the subjects' medical care, it may be appropriate to tell subjects that if such identifiable results are obtained, the subjects will be contacted and asked if they wish to be informed of the results. The decision about whether to provide any results to subjects will depend on the ethical implications of each protocol.

Note: Results obtained from a laboratory that does not meet the standards of CLIA (Clinical Laboratory Improvement Act) may not be used to direct patient care. In these cases, the subject could be notified that an issue has been identified, and that the subject or in some cases the investigator can notify the subject’s physician so that their physician may follow-up with standardized testing when appropriate.

Receiving or Purchasing Tissue/Data from Other Researchers

For protocols in which there are plans to collect specimens or data from outside institutions, the committee will review a “collection” protocol (can use same “repository” protocol form), informed consent /authorization document (if applicable) for distribution to these outside specimen/data collectors and their local IRBs.

A written agreement is required for collector-investigators, which requires written informed consent of the donor-subjects utilizing an informed consent document or a waiver approved by each of the local IRBs. It should also contain an acknowledgment that collector-investigators are prohibited from providing recipient-investigators with access to the identities of donor-subjects or to information through which the identities of donor-subjects may readily be ascertained.

Giving Tissue/Data to Other Researchers

IRB review required: A UVM/UVM Medical Center researcher who is responsible for a tissue or data bank cannot release tissues or data to other researchers (local or not local) until he or she has determined that those researchers have received appropriate approval or determination of exemption from a duly constituted Institutional Review Board (IRB).

Researchers at other institutions or companies are not subject to review by UVM/UVM Medical Center IRB, and the IRB has no jurisdiction over how non-UVM/UVM Medical Center researchers will protect subjects' privacy and interests in the future research. Researchers who are funded by private foundations or industries may be conducting research which is not necessarily subject to Federal regulations protecting human subjects. Therefore, to apply the same level of protection for all subjects involved in UVM/UVM Medical Center research, the IRB generally will not permit providing subject identifiers along with tissues or data to non-UVM/UVM Medical Center researchers. If necessary, the samples/data may be coded, but the key must be maintained at UVM/UVM Medical Center. For those University of Vermont or UVM Medical Center protocols in which there are plans to release tissue or data to an outside institution, a written usage agreement for recipient-investigators is required.

Other researchers at UVM/UVM Medical Center wishing to use samples or data previously collected under an approved protocol should contact the IRB office for assistance with determining what paperwork is required for review.

Specimen Collection as Part of a Larger Protocol

Tissues are routinely used for a variety of tests within treatment and epidemiological protocols, and most researchers are accustomed to describing the sampling procedures and risks in their protocols and consent forms. However, if some of the samples will be saved for unspecified future research, additional discussion is needed in the protocol and consent form. All of the concerns that apply to independent tissue collection protocols apply here as well.

Making Tissue Collection Optional: In treatment studies with a potential benefit for subjects, the IRB recommends that collection of tissues for repositories (as opposed to collection for treatment-related analyses) be made optional. That is, in general, patients should not be denied a promising experimental treatment because they are unwilling to allow their tissue to be banked for unspecified future purposes. The IRB is aware that some national cooperative study groups make banking of samples a condition of study participation. Approval for such repositories will be considered very carefully and denied only when there are over-riding ethical concerns.

Consent within a larger protocol: A consent form should emphasize the major procedures and risks of the research study. If the study primarily involves banking of specimens in respositories for future research use, then the major part of the procedures and risks sections should discuss this long term storage. On the other hand, when banking is done as a small and preferably optional part of a treatment study (a cancer treatment regimen, for example) the concern about banking is relatively small compared to deciding how to treat a life-threatening condition.

One acceptable method of discussing banking within a consent form for a treatment study is to include a separate paragraph between the Procedures and Risks section, briefly discussing the banking and its implications. If banking in a repository is optional, two appropriately labeled lines for initials should be included with the signature section, so that subjects can indicate whether or not they are willing to have specimens banked.

The IRB recommends the following language:

“Biologic Studies: Portions of your tissues which are removed as part of care and are not required for routine diagnosis or treatment may be used now or in the future for research purposes. These tissue samples may be used to learn more about how cancer or other diseases develop and/or may result in new products, tests or discoveries. In some instances, these may have potential commercial value. These tissues to be kept for research purposes will be obtained only at the same time as your regular procedures are performed; you will not have to undergo any special procedures for this purpose. There will be no additional charge, and you will not receive any payment or financial benefit from any products, tests or discoveries. You may also be asked in the future if you are willing to be in additional research studies. You will not be told the results of any future research. Participation in this extra research is voluntary, and if you choose not to allow the extra research it will in no way affect your care on the main study. You may at any time contact the researchers to request that your samples be withdrawn from research use, and any identifiable samples still in their possession will be destroyed. Please indicate whether you are willing to allow this extra research by initialing one of the lines at the end of the form.”

Just before the signature lines in the treatment consent form:

“______ I do not want my tissue and blood samples used for any research or tests other than those needed for the main research study.

______ The researchers may keep my extra tissue and blood samples for future research.

______ I am willing to be contacted in the future about any additional research studies.”

 

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8.4.1 Research Tissue Acquisition Policy

UVM’s IRB has adopted the UVMMC’s 6-1-2014 Tissue Acquisition Policy as stated below.

Specimens obtained as part of research protocols:

“Patients sometimes enroll in research studies and agree to have tissue obtained for study purposes. It is essential however, that sufficient tissue be obtained for complete examination in the Department of Pathology to ensure an accurate diagnosis for the patient even when samples are required for research purposes. Therefore, research protocols requiring tissue that would otherwise be sent to pathology for examination must (i) include procedures for ensuring the adequacy of diagnostic tissue for pathologic examination and (ii) receive approval from the surgical pathology quality assurance subcommittee on research specimens prior to activation. Such protocols must acknowledge that if feasible, tissue diverted from pathologic examination for investigative purposes will be provided to the Department of pathology for diagnostic or other patient management purposes as clinically indicated. Pertinent information for patients regarding the use of their tissue for research purposes (e.g. risks and benefits) must be included in the informed consent for such research studies.”

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8.5 Blood Collection Protocols 46.110

This is a category of expedited protocols that includes only the collection of blood. Researchers conducting bench science often times require human cells for their laboratory research, and they and their staff, will donate blood for these scientific purposes. While the activity of drawing blood is not a “research protocol”, the collection of the cells is for research, and therefore falls under the IRB purview. What follows is guidance for blood collection protocols.

Guidance Blood Collection Protocols

OHRP has ruled that for all Federally-sponsored research, informed consent must be obtained before identifiable specimens may be collected for research purposes. This applies to any research that is done at an institution that receives Federal funding. The following guidance and the Blood Collection Protocol form have been developed to comply with these requirements and to help standardize procedures to establish safe practices in the collection of human blood and human blood products for research purposes.

 

blooddraw

 

Submission of the Blood Collection Protocol for review and approval will assist the IRB in ensuring that donors who are participating are protected.

Blood Collection in Non-Clinical Settings

Blood draws in spaces outside of clinical care areas should be conducted in a room that is separated by a door from bench space, biological safety cabinets or other laboratory equipment that is used to handle or store biological infectious agents. Space utilized for blood draws should be separated from active manipulation of infectious biological agents and active work with hazardous chemical agents prior to the blood draw (for area disinfection purposes), at the time of the blood draw, and until disinfection procedures have been completed after the blood draw.

Blood draw areas must follow all BSL-2 work practices including:

  1. Furniture – Blood draw chair or table should be made of materials that can easily be disinfected (example vinyl or plastic furniture)
  2. Sharps containers – An approved Sharps disposal container should be available in the blood draw area at the point of use. All glass items and needles must be disposed of in an approved Sharps container.
  3. Disinfectant – Bleach solution or an EPA registered disinfectant should be available in the draw area in the event of a spill.
  4. Spill or Emergency Procedure - A procedure to handle spill cleanup or emergency response information should be posted at the point of use.
  5. Biohazardous Waste Disposal - Biohazardous waste bags and boxes must be used to dispose of all plastic ware and personnel protective equipment.
  6. Biohazardous Signage and Labeling – All clinical laboratory spaces must be labeled with a biohazardous door sign designating the space as BLS-2. All equipment used to store and handle human blood and blood products must be labeled with a biohazardous sticker.
  7. Personnel Protective Equipment – Personnel conducting blood draws are required to wear the appropriate personnel protective equipment (PPE). This includes liquid barrier gloves (latex or nitrile), face protection (full face shield or surgical mask and safety glasses) and lab coat or lab gown that can be laundered or disposed in event of a blood splash or spill.

Personnel Conducting Blood Draws

The principal investigator is responsible for verifying that personnel performing blood draws have sufficient training and experience in conducting human blood sampling. Qualifications may include prior experience as a trained phlebotomist, nurse or emergency medical technician. All research personnel conducting human blood draws or work with human blood and blood products must complete blood borne pathogen training on an annual basis. Information on training is available on the University Environmental Safety website or is part of the UVM Medical Center mandatories.

Approved Standard Practices for Obtaining Blood

  1. Healthy adults individuals will be asked to participate in this minimal risk procedure. Education and review of the consent will be performed.
  2. After the consent is signed, the volunteer will be brought to ______________________
  3. Phlebotomy of a peripheral arm vein will be performed by ________________________using sterile procedures and seated position. A sterile bandage will cover the phlebotomy site after the procedure and the arm will be elevated to ensure that bleeding has stopped.
  4. The volunteer will be observed for any lightheadedness, bruising or bleeding during and after the procedure.
  5. If the volunteer is lightheaded, he/she will be reclined and monitored until symptoms resolve.
  6. If the volunteer is asymptomatic after the phlebotomy procedure, he/she will be released.
  7. Any volunteer with any side effects during or after phlebotomy will not be used again to obtain the blood products. In addition, any volunteer that requires more than three attempts to access a vein will also not be used as a volunteer.

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8.6 Research Involving Coded Private Information or Biological Specimens

Basic Policy

Research using private information or biological specimens that is categorized as “human subjects research” can only be conducted after receiving the appropriate Committee review under the normal established guidelines.

There is now federal guidance that clarifies the distinction between (a) research involving coded private information or specimens that does not involve human subjects; and (b) human subject research that is exempt from the requirements of the Department of Health and Human Service (DHHS) regulations. The guidance also provides new definitions of key terms to assist in making these determinations because it fits into specific categories. When conducting research using data or specimens, the human subject determination noted above, the type of application, the informed consent requirements, and the level of review by the IRB depends primarily on one factor: whether the data or specimens are identifiable to the principal investigator or key personnel.

Determinations of whether research involving coded private information or biological specimens is considered to be “human subjects research” must be made by the IRB, not the investigator.

Does Your Proposed Research Involve Human Subjects?

Regulatory requirements (Federal and state) to protect human subjects apply to a much broader range of research than many investigators realize, and researchers using data and/or specimens are often unsure about how regulations apply to their research. Regulatory obligations to protect human subjects would apply, for example, to research that uses –

1. Bodily materials, such as cells, blood or urine, specimens, organs, hair or nail clippings, from living individuals who are individually identifiable to the investigator(s), even if these materials were collected by others;

2. Residual diagnostic specimens from living individuals that are individually identifiable to the investigator(s), including specimens obtained for routine patient care that would have been discarded if not used for research;

3. Private information, such as medical information, about living individuals that is individually identifiable to the investigator(s), even if the information was not specifically collected for the study in question. This includes research on genetic information that can be readily associated by the investigator(s) with identifiable living individuals.

The definition of “human subject” includes, but is not limited to, human organs, specimens, and body fluids from living individuals, as well as private graphic, written, or recorded information about living individuals, if (1) there is interaction or intervention with a living individual to obtain the data or specimens for research purposes, or (2) the identity of the subjects can be readily ascertained by the investigator or other members of the research team.

Research that involves only coded private information/data or coded human biological specimens may not constitute human subjects research under the HHS human subjects regulations (45 CFR Part 46) if:

1. The private information and/or specimens were not collected specifically for the currently proposed research project through an interaction/intervention with living individuals, AND

2. the investigator(s) (including collaborators) on the proposed research cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain (e.g., the researcher’s access to subject identities is prohibited by written repository procedures and policies and/or through an agreement signed between the recipient researcher and the repository providing the data or specimens).

Individuals who provide coded information or specimens for proposed research and who also collaborate on the research involving such information or specimens are considered to be involved in the conduct of human subjects research.

The same data/specimens may be identifiable or not for different researchers. For example, if Researcher A stores or receives data/specimens with a code number and has a key linking the numbers to subjects' identities, the data/specimens are identifiable for Researcher A. On the other hand, if Researcher A passes the data/specimens to Researcher B and there is a written agreement that Researcher A will in no circumstances give identifying information to Researcher B, then for Researcher B's research the data/specimens are not identifiable and not considered research involving human subjects.

Who Determines Whether Human Subjects are Involved in Research

The decisions about when research involving data and/or specimens from subjects is considered human subjects research are complex. The project must be submitted to the IRB for this determination utilizing the form titled “Research Not Involving Human Subjects Review and Determination .”

Retrospective versus Prospective Collection of Data or Specimens

The criteria the IRB must use to determine whether research involves human subjects under this policy are based on the following types of data/specimen collection methods and how the data/specimens are identified.

  • Retrospective data or specimens are data or specimens that are already existing or "on the shelf" when the research is proposed. Specimens or data are considered existing only if they were gathered before the research is proposed. Example: Data previously collected for medical care or specimens that are left over from surgery or previous research studies.
  • Existing, Not Identifiable (i.e., not coded) data or specimens: This category includes data or specimens obtained without identifiers from a data or specimen repository at UVM/UVM Medical Center or elsewhere. Research utilizing such existing coded data or specimens would not be considered “research with human subjects. ” The investigator would need to complete and submit the “Research Not Involving Human Subjects Review and Determination” form.
  • Existing, Identifiable data or specimens: This category includes data or specimens that can be individually identified with the patient/subject and therefore would be considered “human subject research. ” This type of research may meet the federal criteria for exemption from IRB review. See guidance on exempt review in the Research Manual.
  • Prospectively gathered data or specimens: Conversely, data or specimens that will be taken from patients or subjects after proposal of the research are considered to be prospectively gathered.
  • Prospectively Gathered, Not identifiable (i.e., not coded) data or specimens: If you are prospectively obtaining data or specimens which are left over from another purpose (clinical, diagnostic procedures or another research study), and they are not individually identifiable (coded) to the investigator, it may be considered not “research with human subjects.”
  • Prospectively Gathered, identifiable data or specimens: If the data or specimens are to be gathered specifically for the research project, it is considered “human subject research” and would not qualify for exemption, however might qualify for expedited review. See Research Manual for guidance regarding expedited review.

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9. Consent (§____.116)

Legally Effective and Prospectively Obtained Informed Consent and Documentation of Consent

Informed Consent

Informed Consent is an individual’s voluntary agreement, based upon adequate knowledge and understanding of relevant information, to participate in research or to undergo a diagnostic, therapeutic, or preventive procedure.

Informed consent must be obtained from the participant or their legally authorized representative using most recently-approved version of the consent document prior to initiating research activities. Research activities includes protocol recruitment and any screening procedures. Contact with a potential subject for recruitment purposes may be made prior to written consent if the criteria for a waiver of written documentation or an alteration in the process is requested and approved (see section titled Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation).

IRB Review of Consent

The IRB ensures that provisions are made to obtain legally effective informed consent prospectively from each prospective research participant or permission from his/her legally authorized representative,  in accordance with and to the extent required by 45 CFR 46.116 and 21 CFR 50.20.  However, there are circumstances in which the IRB may grant a waiver of informed consent in accordance with Federal regulations. (see section titled Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation for more information.)

Written informed consent is to be obtained unless alternate procedures are approved by the IRB, in accordance with 45 CFR 46.117 and 21 CFR 50.27.  The IRB reviews all informed consent documents to assure the adequacy of the information contained in the consent document, and adherence to Federal regulations regarding the required elements of informed consent.

Consent Requirements/Elements in the Form

An investigator may not involve a human subject in research without first obtaining the informed consent (with HIPAA authorization language included when Protected Health Information (PHI) is used/disclosed) of the subject or the subject's legally authorized representative.  This must be obtained in writing, signed electronically (a written copy must be provided to the subject) or verbally (if the specific criteria as described below are met). In either case, informed consent (and HIPAA, when applicable) must be obtained under circumstances which allow sufficient opportunity to consider participation and that minimize the possibility of any coercion or undue influence.

The information that is given to subjects must be in a language understandable to them or their representative.  Whether informed consent is written or oral, it must not include any exculpatory language through which the subject or representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, sponsor, institution or its agents from liability for negligence.

If genetic materials are to be collected, stored or analyzed, GINA language must be included in the subject consent form.   Language can be found in the IRB consent template located on our forms page.

New and in Effect! As of January 2018 consent forms should contain the following:

A concise summary of study activities, risks, and benefits presented to research participants in advance of the body of the consent document. The IRB will not require re-consent for already enrolled subjects.

The IRB provides instructions and a consent template to assist with consent form development.  The elements are listed below.

 More information coming soon! (Do not reference until the 2018 revised Common Rule takes effect)

There will be new requirements for posting clinical trial consent forms on a publicly available federal website that will be established as a repository for clinical trial consent forms.

Basic Elements of Informed Consent: §____.116(a)

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental.
  2. A description of any reasonably foreseeable risks (physical, psychological, social, legal, or others) or discomforts to the subject.

NOTE: See section titled Elements Found in a Standard Clinical Trial Protocol for additional information regarding GINA.

  1. A description of any benefits to the subject or to others, which may reasonably be expected from the research. If there is no direct benefit to the subject, this should be stated.
  2. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.
  3. A statement describing the extent to which confidentiality of records will be maintained.
  4. For research involving more than minimal risk, an explanation as to whether compensation and any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained. When applicable, standard language from the template must be used as written.
  5. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject.
  6. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled and the subjects may discontinue participation at any time without penalty or loss of benefits.
  7. The name, address, and telephone number of the principal investigator(s) or contact person(s).
  8. The amount of compensation, if any, for participation.
  9. NEW and in Effect! Identifiers might be removed and the de-identified information or biospecimens used for future research without additional informed consent from the subject; or the subject’s information or biospecimens will not be used or distributed for future research studies even if identifiers are removed.

Additional Elements of Informed Consent: §____.116(b)

  1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.
  2. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.
  3. Any additional costs to the subject that may result from participation in the research.
  4. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.
  5. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject.
  6. The approximate number of subjects involved in the study.
  7. When HIV testing is conducted as part of the research procedures, individuals whose test results are associated with personal identifiers must be informed that they will be provided with their test results and provided with the opportunity to receive appropriate counseling. It should also be stated that both HIV and AIDS cases must, by law, be reported to the Vermont Department of Health and disclosure of a positive test may result in discrimination by friends, family, employers, insurance companies and others. See consent template for additional guidance.
  8. NEW and in Effect! 46.116(c)(7) - A statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit.
  9. NEW and in Effect! 46.116(c)(8) - A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions.
  10. NEW and in Effect! 46.116(c)(9) - For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

For consent form document guidance as well as templates for various types of consents, see the Consent and HIPAA Guidance page of the IRB website.

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9.1 Children

For any protocol involving children, the IRB must determine which of four categories (see categories below) of research apply to that study, if any. The IRB will document the rationale for this choice in the minutes.

For subjects less than 18 years of age, their parent(s) or other legal guardians are the legally authorized representatives who may grant permission for their participation in research (in accordance with 45 CFR 46 (children’s subpart). For further information, see the section titled Children in this manual.

Definitions:

1. Assent: An individual’s affirmative agreement to participate in research obtained in conjunction with permission from the individual’s parents or legally authorized representative. Mere failure to object should not, absent affirmative agreement, be construed as assent. Assent is typically conducted with children 11 years of age or older.

2. Children: Any person who has not attained 18 years of age.

The HHS regulations at 45 CFR part 46, subpart D permit IRBs to approve three categories of research involving children as subjects:

Research not involving greater than minimal risk to the children 45 CFR 46.404
To approve this category of research, the IRB must make the following determinations:

  • the research presents no greater than minimal risk to the children; and
  • adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child subjects involved in the research 45 CFR 46.405
To approve research in this category, the IRB must make the following determinations:

  • the risk is justified by the anticipated benefits to the subjects;
  • the relation of the anticipated benefit to the risk presented by the study is at least as favorable to the subjects as that provided by available alternative approaches;  and
  • adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

Research involving greater than minimal risk and no prospect of direct benefit to the individual child subjects involved in the research, but likely to yield generalizable knowledge about the subject's disorder or condition 45 CFR 46.406
In order to approve research in this category, the IRB must make the following determinations:

  • the risk of the research represents a minor increase over minimal risk;
  • the intervention or procedure presents experiences to the child subjects that are reasonably commensurate with those inherent in their actual, or expected medical, dental, psychological, social, or educational situations;
  • the intervention or procedure is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance for the understanding or amelioration of the disorder or condition;  and
  • adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

A fourth category of research requires a special level of HHS review beyond that provided by the IRB.

Research that the IRB believes does not meet the conditions of 45 CFR 46.404, 46.405, or 46.406, but finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children 45 CFR 46.407
If the IRB believes that the research does not meet the requirements of 45 CFR 46.404, 46.405, or 46.406, but finds that it presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children, it may refer the protocol to HHS for review. The research may proceed only if the Secretary, HHS, or his or her designee, after consulting with a panel of experts in pertinent disciplines (e.g., science, medicine, education, ethics, law) and following an opportunity for public review and comment, determines either: (1) that the research in fact satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406, or (2) the following:

  • the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;
  • the research will be conducted in accordance with sound ethical principles;  and
  • adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

For more information on the HHS 45 CFR 46.407 review process see OHRP Guidance, Children Involved as Subjects in Research: Guidance on the HHS 45 CFR 46.407 ("407") Review Process.

Consenting Children

The consent process of children should meet the following Requirements for Assent and Parental Permission:

For research in the categories “Research involving greater than minimal risk…” and “Research otherwise not approvable…” permission is to be obtained from both parents, unless one parent is deceased, unknown, incompetent or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.

The IRB may determine that the permission of one parent is sufficient for research not involving greater than minimal risk or for research that does involve greater than minimal risk, but presents the prospect of direct benefit to individual subjects.

*** The assent of a child is not a necessary condition for proceeding with the research if the IRB finds that the capability of some or all of the children is so limited that they cannot be reasonably consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research. Permission of the parents/guardians is still a requirement.

Parents

Only the parent(s) may grant permission for the child’s participation in research. Assent is to be sought from the child, only after permission has been obtained from one or both of the parents. Grandparents and other relatives or caregivers may not grant permission unless they have been granted formal custody of the child by a court. In such cases, the Principal Investigator (PI) must obtain a copy of the court order as evidence of that person’s authority to grant permission for participation in research on the child’s behalf. See additional information regarding consent process, see below.

Waiver of Consent (and HIPAA Authorization if PHI is involved)

If the IRB determines that a research protocol is designed for conditions or for a subject population, for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), the IRB may waive the consent requirements, provided an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted, and provided further that the waiver is not inconsistent with federal, state or local law. The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risks and anticipated benefits to the research subjects, age, maturity, and condition.

NOTE: The FDA does not typically allow for a waiver of consent when regulated test articles are being used. In the case of emergency care treatment, (not research in an emergency setting) a wavier will be considered, see section on Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation for more information.

Children in State Custody (Wards of State)

According to the Department of Children and Families (DCF) applicable policies and by virtue of the court order granting DCF legal custody of certain children (e.g., foster children), that Department is the agency that is authorized to grant permission for participation in research for children in their custody. The decision of whether to grant permission for research is made on a case-by-case basis by DCF and consent is provided by an appropriate representative of DCF.

If a child has begun research procedures with the consent of a parent but is subsequently placed in the custody of DCF while undergoing research interventions, consent must be sought again from the appointed advocate for the child at DCF in order to continue participation in the research. See additional information in Section on Children.

Emancipated Minor

According to Vermont Statute, an emancipated minor means a minor who:

a. has entered into a valid marriage, whether or not such marriage was terminated by dissolution;

b. is on active duty with any of the armed forces of the United States of America; or

c. has been, by a court of law, ordered emancipated.

In order to become an “emancipated minor” the minor must petition the probate court. There are multiple stipulations that must be met by the minor and the court must find that emancipation would be in the best interest of the minor. If the stipulations are met, the court will issue an order of emancipation.

In certain limited circumstances, it may be appropriate to allow an emancipated minor to consent to participate in a research study in the absence of the permission of a parent or legal guardian if the minor has the sufficient capacity to consent to the procedures involved in the research study. Each situation is judged on a case-by-case basis.

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9.1.1 Children Reaching Legal Age of Consent While Enrolled in a Study Policy

When a child who was enrolled in research with parental or guardian permission subsequently reaches the legal age of consent to the procedures involved in ongoing research, the subject’s participation in the research is no longer regulated by the requirements of 45 CFR part 46.408 regarding parental or guardian permission and subject assent.

The researcher should seek and obtain the legally effective informed consent, as described in 45 CFR 46.116, for the now-adult subject for any ongoing interactions or interventions with the subjects. This is because the prior parental permission and child assent are not equivalent to legally effective informed consent for the now-adult subject.

As long as the participation continues to meet the regulatory definition of “human subjects research” (for example, it involves the continued analysis of specimens or data for which the subject’s identity is readily identifiable to the researcher), then it would be necessary for the researcher to seek and obtain legally effective informed consent of the now-adult subjects.

However, the IRB could approve a waiver of informed consent under 45 CFR 46.116(d), if the project meets the required conditions for a wiaver of consent. The investigator must complete and submit the “Request for Waiver of Informed Consent” form to the IRB for this determination.

The IRB developed a sample consent form for continued participation in a research study which can be found under the “Consent and HIPAA Guidance” section and should be used when consenting the now-adult subjects. Since this document was created by the IRB, it does not require the IRB approval stamp. However, if you wish to change the contents, an amendment would be required prior to use. This consent form is essentially a continuation cover consent that explains why the now-adult subject is being consented at this time. A copy of the originally signed parental permission and assent (if applicable) should be attached to this continuation consent form and presented to the now-adult subject. Another HIPAA authorization must also be obtained at this time. Subjects should be reminded of their right to withdraw from the study including: (a) their right to revoke HIPAA authorization, to the extent that such authorization is revocable under the terms of the informed consent and the authorization signed by the parent(s) or guardian; and (b) their right to revoke any other right granted in the study, (e.g., rights with respect to use of tissue samples) to the extent it would be revocable by the parent(s) or guardian when the subject was a minor.

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9.2 Surrogate Consent for Research (Legally Authorized Representatives)

A legally authorized representative (LAR) is defined in both HHS and FDA regulations as an individual or judicial or other body authorized under applicable law to consent on behalf of a potential participant to participate in the procedure(s) involved in the research (45 CFR 46.102(c) and 21 CFR 50.3(1) respectively).

This IRB guidance applies to both therapeutic (with potential direct benefit to the subject) and non-therapeutic (no direct benefit). 

IRB REVIEW OF LEGALLY AUTHORIZED REPRESENTATIVES FOR PROVISION OF CONSENT FOR RESEARCH

The IRB evaluates both the consent process and the procedures for documenting informed consent to ensure that adequate informed consent is obtained from participants, unless a waiver of consent has been approved by the Committee. The use of surrogate consent for children or adults with impaired capacity to consent requires additional consideration to ensure effective, voluntary consent to participate.

CHILDREN 

See Section 9.1 Children for guidance regarding regulatory requirements specific to consenting children in research.

ADULT SUBJECTS LACKING CAPACITY TO CONSENT 

There are no specific federal regulations concerning the inclusion of adult subjects lacking the capacity to consent.  These vulnerable subjects have the same rights as other individuals to participate in research, but special care must be taken to ensure adequate informed consent.

Some research protocols involving the cognitively impaired specifically focus on the individual’s condition.  Examples include, but are not limited to, patients with dementia, schizophrenia, delirium, mental retardation, bipolar disorder and stroke. Other protocols may include a variety of subjects and only incidentally include individuals with questionable capacity to consent.  In either case, special considerations should be made to ensure that the informed consent process is adequate and appropriate.

The IRB uses a case-by-case approach to approving studies involving surrogate consent. The IRB assesses relevant factors of the proposed study including a potential subject’s consent capacity, the study’s risks, anticipated direct and indirect/scientific benefits, the complexity of the protocol, and the provision of additional safeguards. This type of review process, which is recommended by NIH and based on the framework set forth in Subpart A of the HHS regulations and in FDA regulations on IRBs, is generally a more flexible and comprehensive type of analysis than processes that rely on predetermined categorical criteria, e.g., only studies that provide a direct benefit, or are minimal risk may use a surrogate consent.

ASSESSING CAPACITY TO CONSENT

The researcher must provide details in the protocol submission to allow the determination of whether surrogate consent is allowable. This should include whether the inclusion of subjects with limited capacity to consent is scientifically justifiable (i.e. is the primary goal of the study related to a condition that affects consent capacity; would excluding those with limited consent capacity significantly impact the generalizability of the findings, etc.). The protocol must specify the sequence of steps, and the qualifications of the study personnel, that will be employed to assess capacity to consent and to acquire and document surrogate consent if appropriate.

The assessment of capacity to consent should be specific to the research study. Capacity is generally understood to include at least the following four elements:

  1. Understanding, i.e., the ability to comprehend the disclosed information about the nature and purpose of the study, the procedures involved, as well as the risks and benefits of participating versus not participating;
  2. Appreciation, i.e., the ability to appreciate the significance of the disclosed information and the potential risks and benefits for one’s own situation and condition;
  3. Reasoning, i.e., the ability to engage in a reasoning process about the risks and benefits of participating versus alternatives, and;
  4. The ability to express a choice about whether or not to participate.

The following methods can be used to assess capacity to consent:

  1. A standardized and validated instrument that can be tailored to the specific study protocol, such as the MacArthur Competence Assessment Tool – Clinical Research (MacCAT-CR) developed by Appelbaum and Grisso (1995) is available for purchase.
  2. A post-consent quiz documenting the subjects’ knowledge of critical elements in the informed consent form - i.e., nature of the illness being studied, voluntary nature of participation, ability to withdraw at any time, consequences of withdrawing, possible risks and benefits of participation, procedures involved, time required, confidentiality, and whom to call with any questions.  For subjects who score less than perfect on the initial presentation, educational procedures may be employed to raise their understanding to sufficient levels for them to make a meaningful choice about participating.  Such procedures may include simple repetition of the relevant information in the consent form or more detailed explanations of items that the subject has difficulty understanding.  For examples of educational procedures and the content of such quizzes, see Carpenter et al. (Arch Gen Psychiatry, 2000, 57:533-538), Dunn and Jeste (Neuropsychopharmacology, 2001, 24:595-607), Dunn et al. (Am J Psychiatry; 2001; 18:1911-1913), Dunn et al. (Am J Geriatric Psychiatry, 2002 Mar-Apr;10(2):207-11.), or Wirshing et al. (Am J Psychiatry; 1998; 155: 1508-1511). 
  3. The study investigators may develop and suggest alternative procedures for evaluating the presence of decision-making capacity, - e.g., someone outside the research team making the evaluation as to the potential participant's decisional capacity. 

PLAN FOR OBTAINING INFORMED CONSENT FROM SURROGATE

Protocols must include details about the proposed use of surrogates to provide informed consent. Suggested language is below:

  • Whenever possible, investigators will attempt to obtain informed consent directly from the subject.
  • If the potential research subject is unconscious or otherwise obviously lacking in decision-making capacity, the investigator shall document that observation in the research record.
  • The researcher will document the process used to determine who was able to provide surrogate consent.
  • If the potential research subject has questionable capacity to consent but is not unresponsive, the investigator will describe the research to the subject and perform and document an assessment of the participant’s capacity to provide consent.
  • If lack of decisional capacity is evident, the investigator shall inform the potential research subject of the investigator’s intent to obtain surrogate consent. If the subject expresses resistance or dissent to either study participation or to the use of surrogate consent they will be excluded from the study.

UVM MEDICAL CENTER POLICY ON SURROGATE CONSENT

The IRBs for UVM and The UVM Medical Center use the same standards for determining who can provide surrogate consent for research.

Specifically, consent may be given by:

  1. The decision-maker designated by the patient in a Living Will or Durable Power of Attorney for Health Care (“Advance Directive”);
  2. A judicially-appointed guardian if the court order explicitly grants the guardian clinical decision-making authority pursuant to 14 V.S.A. § 3069 (c ) (2);
  3. If the patient has not designated a decision-maker in his/her Advance Directive, consent may be obtained from a spouse, civil union partner, adult child, adult sibling, or other family member/friends. Providers should exercise their professional judgement when determining which family member(s) should be consulted as the patient’s surrogate decision-maker. In general, when determining who should serve as the surrogate decision-maker, providers should assess which individuals best knows what the patient would want in a given circumstance (i.e. the individual best equipped to offer a substituted judgement)

Please note that medication to treat psychiatric illness is not an allowable intervention when a potential subject is unable to give informed consent.

Additional Considerations

Per FDA regulations: A verbal approval does not satisfy the 21 CFR 56.109(c) requirement for a signed consent document, as outlined in 21 CFR 50.27(a). However, it is acceptable to send the informed consent document to the legally authorized representative (LAR) by facsimile and conduct the consent interview by telephone when the LAR can read the consent as it is discussed. If the LAR agrees, he/she can sign the consent and return the signed document to the clinical investigator by facsimile.

If a study that involves subjects who lack the capacity to consent takes place over extended periods of time, the researcher should consider whether and when periodic re-consenting of individuals is required to assure that a subject’s continued involvement is voluntary. The IRB may require that the Investigator re-consent subjects after taking into account the study’s anticipated length and the condition of the individuals to be included (e.g., subjects with progressive neurological disorders). Additionally, the IRB considers whether and when to require a reassessment of decision-making capacity.

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 9.3 Cases of Physical Compromise   

A person who can understand and comprehend spoken English, but is physically unable to talk or write, can be entered into a study if they are competent and able to indicate approval or disapproval by other means. If (1) the person retains the ability to understand the concepts of the study and evaluate the risk and benefit of being in the study when it is explained verbally (still competent) and (2) is able to indicate approval or disapproval to study entry, they may be entered into the study. The consent form should document the method used for communication with the prospective subject and the specific means by which the prospective subject communicated agreement to participate in the study. An impartial third party should witness the entire consent process and sign the consent document.

This consent process must be approved prior to use.  Please explain that the subject will be assessed for their comprehension and understanding and asked if they are able to sign and date for themselves.  If they can understand but cannot sign, an impartial witness will be made available to witness the discussion and the agreement of the subject to participation.  If they are able to sign and date for themselves, no witness will be necessary.   The witness cannot be the same person who is obtaining the consent, it has to be someone impartial.  Below is an example of the signature page that may be appended to the approved consent in these situations.  

_________________________________________                                                 __________
Signature of Subject (mark here with "X" if unable to write)                                   Date

_________________________________________
Name of Subject Printed (research staff may complete if subject is unable to write)

_________________________________________                                                  _________
Impartial Witness (to be used in the event the subject is unable to write)                  Date

_________________________________________                                                  _________
Signature of Principal Investigator or Designee                                                         Date

_________________________________________
Name of Principal Investigator or Designee Printed

 

 

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9.4 Informed Consent and HIPAA Authorization Process for Non-English Speaking Individuals

The Department of Health and Human Services (DHHS) regulations for the protection of human subjects require that informed consent information be presented in "language understandable to the subject," and, in most situations, that informed consent be documented in writing (45 CFR §46.116 and §46.117).

In order for non-English speaking subjects to participate in a research study, steps must be taken to assure true informed consent is obtained. This does not simply mean that a form is signed, but rather that steps are taken to assure the study and voluntary nature of the research is understood by the subject. A translator may need to be involved in the informed consent discussion and a translated consent document may be needed. Further, the IRB may require the investigator to submit a back-translation of the informed consent.

If the majority of subjects are expected to be non-English speaking, use of the Long Form Consent and Authorization Process is required.

If the protocol is already approved for English speaking subjects and a non-English speaking subject presents for participation, the Oral Translation with Short Form Consent Process and Authorization Process may be used. To do this, researchers must submit an amendment to include a non-English speaking individual as a subject addressing all of the requirements listed in that section.

Long Form Consent and Authorization Process §46.117(b)(1) (majority of subjects)

When the subject population of any research study is expected to include a significant number of subjects who are not fluent in English but are fluent in another language, the IRB requires a full translation of the English version of the approved consent document (a “Long Form Consent Document”) along with the translator’s documentation of qualifications.

Note: Interpreter Services at UVMMC meet the standards, therefore, additional documentation is not required. We do, however, require documentation of qualifications for any other translator services.

IRB Review

In addition to the standard initial review submission materials, submit the following:

1. English language version of consent (it is recommended that you hold on translation until after the IRB has approved the English version)

2. A plan for ensuring that the subject understands the requirements and the voluntary nature of the research

The following items must be resubmitted for final approval of the foreign language documents:

1. Foreign language version of the consent.

2. Documentation describing the qualifications of the translator and the date of translation.

Long Form Consent Documents – Request for Back- Translation

If the research is deemed “high” risk or is very complex, or there are other relevant concerns, the IRB reserves the right to request that the foreign language consent be translated back into English to ensure the foreign language consent is written in understandable terms and contains all key elements of consent.

The IRB requires documentation that this back-translation was done by a different translator than the one who did the original translation and documentation of that second translator’s qualifications is required as well.

Consent and Record-keeping Requirements with Translated Long Form

1. Conduct the subject's informed consent process with the researcher and a translator fluent in both English and the foreign language present

2. The subject signs the foreign language informed consent document

3. The researcher or designee signs the informed consent document

4. The translator (or other witness fluent in both languages) signs the informed consent form

5. The subject is given a copy of informed consent form

6. A copy of the signed documents are maintained in the study records

7. A copy of the signed documents should be included in the subject's medical records if that is the standard practice for this particular study

Oral Translation with Short Form Consent and Authorization Process (single subject)

Alternatively, §46.117(b)(2) permits oral presentation of informed consent information in conjunction with a short form written consent document in the subject’s language (stating that the elements of consent have been presented orally). Additionally, the subject is provided with the IRB-approved English version of the consent form.

Typically this option is used when a single subject is found to be eligible to participate in research and there is no long form consent translation. A witness to the oral presentation is required.

IRB Review

Submit the following for review:

1. Amendment form

2. Request for Waiver or Alteration of Informed Consent/Authorization/Documentation

3. English version of short form (template located on our forms page)

4. Foreign language version of short form

5. Documentation describing the qualifications of the translator(s) and date of translation.

6. IRB-approved version of the English language version of the consent form for the protocol

7. A plan for ensuring that the subject understands the requirements and the voluntary nature of the research

Consent and Record-keeping Requirements when using a Short Form Informed Consent Document

Per the Office of Human Research Protections (OHRP), the following steps must be followed after IRB approval.

  1. Conduct the subject's informed consent process with the researcher, a witness, and a translator fluent in both English and the foreign language present
  2. The subject signs the 'short form' informed consent document
  3. The researcher signs the IRB-approved English version of the informed consent document
  4. The witness (fluent in both languages) signs BOTH the short form and the written informed consent form. (Note, the translator may also serve as the witness or the investigator, but not as the investigator and the witness and the translator).
  5. The subject is given a copy of the signed short form and signed written summary/informed consent form
  6. Provide the English version of the signed informed consent form even though the subject may not understand English.
  7. A copy of the signed documents are maintained in the study records along with clear documentation of the consent process and who was involved. (consent process documentation form is available on the IRB website)
  8. A copy of the signed documents should be included in the subject's medical records if that is the standard practice for this particular study.

Any deviation from these alternatives requires review and approval by the IRB.

Effective Communication During Study Participation

In order for consent to be legally effective, the subject must be provided with all relevant research-related information and must clearly understand such information. When non-English speaking subjects are being invited to participate in a study, investigators must ensure that there is adequate communication between the research team and the subjects.

Unless the principal investigator or a member of the research team is fluent in the prospective non-English speaking subject’s language, a translator will be necessary to facilitate the conversation during the consent process and for communication throughout the course of the study. Translators should be fluent in English as well as in the language of the non-English speaking subject.

Other Considerations

Recruitment materials such as flyers must be translated in order to accommodate expected non-English speaking subjects (i.e., a significant number of subjects who are not fluent in English). All translations of recruitment materials must be completed by a certified translator and approved by the IRB prior to their use.

Study instruments may be in English and translated orally by a translator or a member of the research team who is fluent in the language spoken by the non-English speaking subject. If an investigator prefers to have any study instruments translated, the translations must be completed by a certified translator and approved by the IRB.

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9.5 Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation §____.116(c)

Non-FDA Regulated Research

Waivers: 45 CFR 46.116(c)(d) In some research, written or verbal consent is not possible. A typical example would be retrospective record or pathology reviews for limited information that is not sensitive in nature and the data are derived from clinically indicated procedures. Consent is not possible because the subjects are not available to sign a consent form.

Alterations: 45 CFR 46.116(d) In some research, an alteration of the individual’s informed consent or elements of the process may be waived. An example would be when research requires deception. In these cases, some of the elements of informed consent are met but not all. Information typically held would be the basis for the research and subjects are later debriefed.

The requirement to obtain written or verbal informed consent may be waived or altered if:

a. The research involves no more than minimal risk to the subjects.

b. The waiver or alteration will not adversely affect the rights and welfare of the subjects.

c. The research could not practicably be carried out without the waiver or alteration. AND

d. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

In the case of Emergency Use for Treatment, a waiver will be considered, see applicable section below.

To apply for a waiver of written or verbal informed consent, the Principal Investigator must complete Section I of the Request for Waiver of Informed Consent/Authorization/Documentation form and submit it to the IRB with the other initial submission documents. The IRB will evaluate the request to ensure that the waiver criteria set forth above are met. If the waiver is granted, then the waiver approval signed by the IRB chair or designee shall be returned to the principal investigator.

Note: If the protocol requires protected health information (PHI) and you are applying for a waiver of consent, then a waiver of authorization must also be requested. To do this, complete both Sections I and II of the Request for Waiver of Informed Consent/Authorization/Documentation. If there is no protected health information, HIPAA regulations do not apply and a waiver of authorization would not be required. See additional information under the Health Information Portability and Accountability Act section.

FDA-Regulated Research

FDA regulations have historically not permitted any waiver or alteration of consent only under very strict conditions as described below and in these two regulatory sections Emergency Use of a Test Article 21 CFR 50.23 (opens in a new window) and Emergency Research 21 CFR 50.24 (opens in a new window).

In July 2017, FDA released new guidance IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects (opens in a new window) to allow for waiver of informed consent only for certain FDA-regulated minimal risk clinical investigations. This is to facilitate investigator’s ability to conduct studies that may contribute substantially to the development of products to diagnose or treat diseases or conditions, or address unmet medical needs. The FDA intends to revise its informed consent regulations to add this waiver or alteration under appropriate human subject protection safeguards to the existing exceptions from informed consent. However, until FDA promulgates these regulations, the FDA will not object to an IRB approving a waiver or alteration of consent under the criteria noted previously.

Emergency Use for Treatment (21 CFR 50.23)

If your protocol includes an FDA-regulated test article (drug or device), an exemption from the consent requirement is permitted for “Emergency Use for Treatment”. See section Emergency Use of an Investigational Drug or Biologic or Investigation Device for more information.

Emergency Research (21 CFR 50.24)

Emergency research is planned research involving human subjects who have a life-threatening medical condition that necessitates urgent intervention (for which available treatments are unproven or unsatisfactory), and who, because of their condition (such as traumatic brain injury) cannot provide informed consent.

Proposed research activities which contain an exception to consent for emergency research, referred to as an “Emergency Research Consent Waiver,” must meet the strict limited conditions set forth by FDA regulation.

Waiver of Documentation of Informed Consent

45 CFR 46.117(c)In some research, verbal or implied consent of the subject is sufficient and a signed consent form is not necessary. A typical example would be a mailed survey with a cover letter explaining the research. The receipt of a completed survey implies that the subject wanted to participate. The requirement for the investigator to obtain a signed consent from some or all subjects may be waived if:

a. The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context.

OR

b. The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. All subjects, however, must be asked whether they want documentation linking them with the research. The subject's wishes will govern and should be adequately documented, regardless of final decision.

In cases where the documentation requirement is waived, the investigator may wish to provide the subjects with a simply written statement or information sheet that describes the research. This written statement must be reviewed and approved by the Committee prior to use. See forms page on our website for template. For protocols where verbal consent is obtained, the principal investigator or a research team member must document in the research file that verbal consent was obtained. See forms page on our website for consent process documentation form.

To apply for a waiver of consent documentation, the principal investigator must complete Section III of the Request for “Waiver of Informed Consent /Authorization/Documentation” form. The IRB will evaluate the request to ensure that the waiver criteria set forth above are met. If granted, the waiver is approved by the IRB chair or designee and will be returned to the principal investigator.

UVM Waivers Cannot be Used at Other Institutions

Waivers approved by UVM are specific to covered entities under the UVM IRB purview, which are UVMMC and the UVM Luse Center. UVM waivers are not recognized by other covered entities and therefore, cannot be applied to other hospitals or clinics. Consent from the subjects would need to be obtained prospectively or you need apply for a waiver from an associated IRB at that institution.

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9.6 Consent Process for Legally Blind or Impaired Vision Research Participants

For subjects who cannot read the consent materials due to blindness, or the subject's legally authorized representative (LAR) is legally blind, the following the consent process is recommended:

  • The consent and HIPAA authorization forms should be presented to potential subjects orally and the potential subject provided with an audiotape or videotape of the process if possible.
  • Have an impartial witness observe the consent process, such as a subject advocate or someone not affiliated with the research team. The witness must be a person who is independent of the research team and cannot be unfairly influenced by people involved with the research, who does not have a coercive relationship with the participant, who attends the informed consent process.
  • If potential subjects have access to equipment that can read the consent document for them, provide sufficient time for them to review the consent document independently of the research team.
  • As would be expected for any consent process, ensure sufficient time is allowed for questions to be asked by the potential subjects, subject's representative, and research team to ensure that the consent process was clear and effective.
  • The research documents should include a statement that the forms were read to the subject by a member of the research team designated to obtain informed consent.
  • It is the investigator's responsibility to judge the subject's comprehension of the consent information including the understanding the participation is voluntary and that that subject has the right to withdraw at any time during the study. If the investigator doubts the subject's consent comprehension, he or she should not enroll the subject in the study.

Example signature block for witness signature

Add on as needed to the last page of the consent if a witness will observe the consent process. E.g., blind subject. Do not add to every consent document unless every subject will have a witness to the consent process.

Signature Block

My signature below documents that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject, and that consent was freely given by the subject.

 

Signature of witness to consent process

Date

 

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9.7 Guidance for Researchers Using Deception or Incomplete Disclosure in Research

This guidance describes the special responsibilities imposed on the investigator and the considerations required of the IRB when research involves deception or incomplete disclosure.

Deception studies intentionally provide misleading or false information. Misleading or omitted information might include the true title of the research, the purpose of the research, the role of the researcher, performance feedback given during the research, or what procedures in the study are actually experimental. Deception and concealment increase ethical concerns because they interfere with the ability of the participant to be fully informed at the time of consent. However, deception may be necessary in some cases.

Examples of deception include:

• Participants complete a quiz and are falsely told that they did poorly, regardless of their performance.

• An anxiety study, in which participants are told to expect mild pain during the course of the study, but no painful procedures are administered.

Examples of Incomplete disclosure include:

• Participants are asked to take a quiz but they are not told the research question involves how background noise affects their ability to concentrate.

• Participants are told they are completing a survey to evaluate customer service when the true purpose of the study is to correlate psychological responses with patient care satisfaction.

It is important to note that in some cases the IRB does not consider withholding the true hypothesis from the participant as significant deception.

Regulations

Federal regulations permit but establish limitations on the use of deception. The Investigator must provide for IRB review and approval their scientific and ethical justification for deceptive procedures. The missing information should not increase the risks to participants in the study, and when possible participants must be fully debriefed as soon as the research methodology allows. Participants must have the opportunity to ask questions about the new information and must be given the opportunity to withdraw from the study as well as the opportunity to have their data removed. Deception may not be utilized to obtain enrollments.

According to guidance provided by the Office for Human Research Protections (OHRP), the use of deception requires a request to waive certain elements of informed consent. According to the regulations the IRB may approve a consent procedure, which does not include, or which alters, some or all of the elements of informed consent IF it finds and documents that:

(1) The research involves no more than minimal risk to the subjects;

(2) The waiver or alteration will not adversely affect the rights and welfare of the subjects;

(3) The research could not practicably be carried out without the waiver or alteration; AND

(4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

(5) The research is not FDA-regulated.

To apply for an alteration of the consent process to waive certain elements of consent, the Principal Investigator must complete Section I of the Request for Waiver of Informed Consent/Authorization/Documentation form. The completed form along with a debriefing script (if appropriate) must be submitted for IRB review. The IRB will evaluate the request to ensure the waiver criteria set forth above are met.  If the alteration of consent processes is granted, this will be reflected in the approval notification.

PI’s may access the UVM waiver/alteration of informed consent in the IRB forms page.

Consent Form Considerations

If the study design allows, participants should be told during the original consent process that some information is being withheld or is incomplete, and that they will receive more information after the research is over. However, researchers often believe that even vague references to hidden purposes will affect the participants' behavior and make the study impracticable. Investigators should either add such language to their consent forms when it is possible or note in their protocols why it is not feasible to do so. The consent form can omit information, but investigators should avoid deliberate misinformation or falsehoods within the consent.

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9.7.1 Debriefing

When an investigator uses deception or incomplete disclosure, regulations require that participants be debriefed as soon as possible after participation in the study, or at the end of the study with appropriate justification provided. Requesting to delay debriefing to the end of the study and may require a Full Committee Review. Participants should be given a simple, clear and informative explanation of the rationale for the design of the study and the methods used, and participants should have the opportunity to ask questions. There are rare cases when debriefing may be impossible or may do more harm to research participants than the deception itself – in those cases the IRB may decide that debriefing is not appropriate. Click here for Microsoft Office document icon UVM’s debriefing template (DOC).

The primary goals of a debriefing process are to:

  • inform participants of the true goals of the research study,
  • remove any effects of false information they were given,
  • educate participants about the research process, why deception is sometimes necessary
  • make participants feel that they are an important part of the research process.

The investigator may decide (or the IRB may require) that the debriefing include an option for participants to withdraw their data from the study after they learn the true nature of the research, if it is of a particularly sensitive nature. (e.g., the withheld aim of the study is that the researcher is measuring participants’ racism).

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9.7.2 Additional IRB Considerations when using Deception or Incomplete Disclosure in Research

The American Psychological Association (APA) has also developed a code of conduct for deception in research. According to the APA, deception in research requires that the researcher:

(1) apply a cost-benefit analysis that explicitly considers the potential for harm created and/or exacerbated by the use of deception,

(2) consider alternative methods, and

(3) fully explain the nature of the deception at the conclusion of the study or explicitly justify withholding such information. In all cases, the safety and comfort of the participant should be of paramount concern.

When IRB members are evaluating the use of deceptive techniques, IRB members should be considerate of the APA’s code of conduct as well as the following:

  • The scientific value and validity of the research
  • The efficacy of alternative procedures
  • The certainty that deception does not extend to influence participants' willingness to participate
  • The possibility of experimentally induced harm and the ability of the proposed procedures to remove such harm through debriefing
  • The potential of deception to facilitate unwanted and inappropriate invasions

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9.8 Media Consent

If a subject consents to participate in a protocol and then agrees to be interviewed regarding their research participation, another consent document must be signed. This consent document is referred to as “media” consent. It is required because the originally signed protocol consent form states that the subject’s information will be protected and kept confidential. The “media” consent indicates that they are freely giving up that protection by agreeing to take part in the interview. This applies when there is a direct or indirect interview, videotaping, and photographs of the individual for TV/radio broadcast or publication. This “media” consent is located on our website forms page and should be completed by the subject prior to the interview. The IRB does not need to review this activity.

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10. Data Protection Regulations

 

10.1 HIPAA

HIPAA refers to the Health Insurance and Portability Act of 1996.  It is a broad federal law, only part of which is intended to protect the privacy of healthcare information.  It is divided into three parts:  portability, accountability, and administrative simplification.  There are several sets of HIPAA regulations.  The most important regulation under HIPAA for research are the privacy regulations, often referred to as the Privacy Rule.  The intent of the Privacy Rule is to protect the private individual’s health care information.  It defines the means by which individuals/human research subjects can be informed of how their health information will be used or disclosed and it gives individuals a number of rights with regard to their health information.  This information is contained in the medical consent template.  The consent/authorization must be signed by the subject prior to beginning any research activities. See our HIPAA Research FAQs for more information.

The HIPAA Privacy Rule comes into play when you are conducting research within a covered entity or when you are receiving identifiable healthcare information directly from a covered entity.  A covered entity is any institution that is providing healthcare to individuals, such as UVM Medical Center.  If your protocol is being conducted at UVM Medical Center or you are receiving healthcare information from UVM Medical Center, HIPAA materials will be required.   In some cases, when consent is waived  or documentation of consent is waived, HIPAA  may also be waived or altered (waiving written authorization), see above, Applying for a Waiver of Documentation, an Alteration or a Waiver of Consent.

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10.2 Waiver, Partial Waiver or Alteration of HIPAA Authorization 45 CFR 164.512

UVM Medical Center and the UVM LUSE Center may use or disclose PHI for research purposes without patient authorization if the IRB (functioning as the Privacy Board) has approved a “Waiver of Authorization.”

In order to use or disclose PHI with a waiver of authorization, the IRB or Privacy Board must find:

(a) The use or disclosure of PHI involves no more than minimal risk to the privacy of individuals, based on, at least, the presence of the following criteria:

(1) An adequate plan to protect the identifiers from improper use and disclosure;

(2) An adequate plan to destroy the identifiers at the earliest opportunity consistent with conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise required by law;

(3) Adequate written assurances that the PHI will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of PHI would be permitted under the HIPAA privacy rule.

(b) The research could not practicably be conducted without the alteration or waiver; and

(c) The research could not practicably be conducted without access to and use of the protected health information.

An alteration of HIPAA Authorization may be granted when there is also a request to waive the documentation of consent.

To apply for a waiver or alteration of authorization for research purposes, the Principal Investigator must complete Sections I and II of the “Request for Waiver of Informed Consent /Authorization/Documentation” form and submit it to the IRB with the initial submission documents. The IRB will evaluate the request to ensure that the waiver criteria set forth above are met. If granted, the waiver is approved by the IRB chair or designee and will be returned to the Principal Investigator.

Note: List of PHI IdentifiersThat Make Health Information Identified

1. Names.

2. All geographic subdivisions smaller than a state, including street address, city, county, precinct, ZIP Code, and their equivalent geocodes, except for the initial three digits of a ZIP Code if, according to the current publicly available data from the Bureau of the Census:

  • The geographic unit formed by combining all ZIP Codes with the same three initial digits contains more than 20,000 people, and
  • The initial three digits of a ZIP Code for all such geographic units containing 20,000 or fewer people are changed to 000.

3. All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older. The population of a zip code can be identified on the web site of the U.S. Census Bureau.

4. Telephone numbers.

5. Facsimile numbers.

6. Electronic mail addresses.

7. Social security numbers.

8. Medical record numbers.

9. Health insurance plan beneficiary numbers.

10. Account numbers.

11. Certificate/license numbers.

12. Vehicle identifiers and serial numbers, including license plate numbers.

13. Device identifiers and serial numbers.

14. Web universal resource locators (URLs).

15. Internet protocol (IP) address numbers.

16. Biometric identifiers, including fingerprints and voiceprints.

17. ull-face photographic images and any comparable images.

18. Any other unique identifying number, characteristic, or code, unless permitted by the individual

Request for Waiver of Informed Consent /Authorization /Documentation Form

Note: The “Request for Waiver of Informed Consent /Authorization/Documentation (DOCX)” Form is a form utilized by the Committees on Human Research to review the specifics of any requested waiver of normally required research materials. If you are applying for a waiver of both consent and authorization, only one form need be completed and submitted. We recommend that you contact our office for assistance prior to protocol submission.

All the necessary forms are located in the IRB Forms page and should be downloaded each time you need one.

Request for a Partial Waiver of Authorization for Recruitment Purposes

Recruitment of potential research subjects at UVM Medical Center/UVM is a regulated research activity and must be conducted in accordance with the policies and procedures promulgated by the UVM Institutional Review Board.

A UVM Medical Center Health Care Provider or his/her agent may, without patient authorization, review the medical records of patients with whom he or she has a current clinical relationship to determine whether they meet the eligibility criteria for enrollment into a research study, and then contact prospective subjects directly by telephone or by letter, explaining the research study and requesting a decision concerning the individual’s potential interest in the study.

A “UVM Medical Center Health Care Provider” is defined as a licensed health care professional who is employed on a full-time or part-time basis by UVM Medical Center, regardless of whether or not the provider holds a faculty appointment at UVM or has an employment relationship with UVM. This includes the provider’s immediate practice group or coverage group.

A “current clinical relationship” shall be deemed to exist whenever the patient, at the time the recruitment activity is taking place, is considered to be under the care of the provider engaged in the recruitment activity or a member of the provider’s immediate practice group or coverage group.

An “agent” is defined as an individual who is under the direct supervision and control of the UVM Medical Center Health Care Provider engaged in the recruitment activity or under the direct supervision and control of a member of the provider’s immediate practice group or coverage group.

In all other cases, UVM Medical Center may only use or disclose PHI for recruitment purposes if the use or disclosure has been authorized by the patient or the researcher has obtained an IRB waiver of authorization. To obtain a partial waiver for recruitment purposes, complete form “Request for Waiver of Authorization for Recruitment Purposes” and submit to the IRB at the time of initial submission.

Request for Partial Waiver of Authorization for Recruitment Purposes Form

“Request for Partial Waiver of Authorization for Recruitment Purposes (DOC)” Form is a form utilized by the Committees on Human Research, which are operating as the Privacy Board for UVM Medical Center, to waive HIPAA Authorization, prior to enrollment, for recruitment purposes only. Every partial waiver of Authorization for recruitment purposes approved by the Committees/Privacy Board must have a “Request for Partial Waiver of Authorization for Recruitment Purposes” Form.

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10.3 European Union (EU) Participants and EU General Data Protections (GDPR)

The European Union’s General Data Protection Regulation (EU GDPR) regulates the use, access, collection, and processing of all personal data from the European Economic Area (EEA). The GDPR apply in the 28 member states of the EU and the three additional countries (Iceland, Liechtenstein, and Norway).

Data to which GDPR applies is broader than that covered under the Health Insurance Portability and Accountability Act of 1996 (HIPAA). It applies to all personal data across all sectors of the economy, not only health care; there is no concept of a covered entity.

GDPR applies if an organization or individual is established in the EEA and acts as a data controller or processor (defined below), the organization or individual offers goods or services to individuals in the EEA, or an organization or individual monitors the behavior of individuals (multisite research or mobile application research) in the EEA.

GDPR Definitions

Controller (sponsor): the controller determines alone or jointly with others the purposes and means of processing personal data. Regulated under GDPR. Controllers provide notices to data subjects, responds to subject rights, appoints representative in EEA, notifies supervisory authorities and data subjects of data breaches, and maintains records of processing.

Processor: Processes personal data on behalf of the controller. Regulated under GDPR.

Data Subject: means an identifiable natural person who is either a citizen of the EU country (whether physically in the EU or in the US) or a US citizen who is physically in the EU for which we collect or process personal data.

EEA Countries: consist of the following: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom. Please note the UK is still part of the EU.

Identifiable Natural Person: means a person (not an organization or company) who can be identified, directly or indirectly, in particular by reference to an identifier.

Identifier: includes data elements such as a name, an identification number, location data, an online identifier or to one or more factors specific to the physical, physiological, genetic, mental, economic, cultural or social identity of that natural person.

Personal Data: under GDPR means any information that can be used to identify a natural person that relates to an identified or identifiable nature person (data subject) regardless of the medium in which is exists (i.e., paper, electronic, recorded, video, audio) and regardless of how/where it is stored (i.e., server, laptop, thumb drive, on the cloud, paper files in a file cabinet, etc.)

How could GDPR impact research at UVM

1. If you are collecting or will collect “identifiable personal data” from participants residing in the EEA on or after May 25, 2018, your project will be subject to GDPR.

If a PI at UVM/UVMMC is the sponsor of a multi-site, international protocol that involves one of these countries, GDPR applies because data is being exchanged and services are being provided through a Clinical Trial Agreement between the US-based investigator (sponsor) and the EEA study site. In this instance, the UVM PI must ensure that appropriate notice about the GDPR is provided to those EEA subjects. Since the single IRB requirement does not exist for international protocols, local EEA IRB review would be required. It is assumed that the notice to EEA subjects will be enforced by the local IRB. However, the UVM PI must be aware and understand this requirement.

2. If a UVM/UVMMC investigator conducts research in the U.S. and transmits identifiable personal data to sponsors, servers, or data core facilities within the EEA on or after May 25, 2018, your project will be subject to GDPR.

In this instance, the sponsor organization is established in the EEA and acts as a data controller or processor. Sponsor is offering goods or services by virtue of a Clinical Trial Agreement. The sponsor of the protocol will be responsible to provide their notice to the UVM researcher for distribution to subjects. The privacy notice must include contact information for the sponsor in the event that a subject wishes to apply any of their data privacy rights. It is not appropriate to list the local privacy officer as he/she does not administer the EU GDPR. The requirement to include a signature of the subject on the notice is at the sponsor’s discretion. The IRB does not require signature on the privacy notice. The sponsor’s notice and any script used to explain this regulation to subjects in the US is to be submitted to the IRB for review.

3. UVM student projects collecting identifiable personal data from EEA subjects on or after May 25, 2018 may be subject to GDPR.

It is not clear that UVM student projects would be providing any goods or services, typically these are survey projects and there is no Clinical Trial Agreement. Contact the office in these instances.

4. UVM mobile research studies that collect personal data from EEA residents may also be subject to the GDPR.

For instance, US-based entity provides mobile application to EEA residents for collection of research data. UVM/UVMMC is offering good or services but there may not be a Clinical Trial Agreement. Contact the office in these instances.

5. European governmental grants or contracts may require compliance with GDPR.

Personal data flows with EEA direct grant awardees or sub-recipients should be scrutinized to see if they involve offering services to EEA data subjects. Contact SPA or RPO to assist in these instances.

What if I am not collecting personal data from individuals in the EEA?

In short, GDPR would not apply. Research studies may not involve the receipt of personal data because the data received may not relate to an identified or identifiable natural person. For example, studies that do not collect information that is linked to a subject’s identity, such as anonymous surveys in which the identities of survey subjects cannot be traced, would not involve the receipt of personal data.

What if I am only receiving coded data?

The GDPR considers key-coded data to be “personal data” and refers to key-coded data as “pseudonymized data”. This is in contrast to the position under many U.S. research and privacy laws, such as the Common Rule and HIPAA. Pseudonymized data are regarded as identifiable personal data and therefore remain subject to the GDPR’s protections, even when in the hands of a person who lacks the key needed to link the data to the data subject’s identity.

Is it possible to de-identify data so that GDPR does not apply?

The GDPR does not apply to data that have been “anonymized.” However, for data to be anonymized, the GDPR requires that there be no key to re-identify the data. For example, if UVM serves as the sponsor of a research study with a site located in the EEA and receives only key-coded information from the EEA site, the key-coded data from the EEA site remain “personal data” in the hands of UVM. This is the case even if UVM has no access to the key needed to re-identify the coded data. Unlike in HIPAA, there is no “safe harbor” under the GDPR to which data can be rendered de-identified by removing a specific list of identifiers. Rather, anonymization is judged on a facts and circumstances basis taking into account all the means reasonably likely to be used, such as singling out, either by the controller or by another person to identify the natural person directly or indirectly. Given this definition, anonymization is an extremely high standard that is difficult to meet in practice.

I have heard that subjects have additional rights under the GDPR. Is that true?

Yes, it is. The GDPR creates a range of rights that are available to research subjects under certain situations. Some of the rights under the GDPR include the right that research subjects can obtain copies of all of their personal data and have the right to withdraw consent to further processing of their personal data. Upon withdrawal of consent for research, one can no longer retain the personal data for the purpose of research, including in pseudonymized (key-coded) form. However, one may retain the data if necessary for legal compliance (i.e., for adverse event reporting). Also, the researcher could continue to process the data for research purposes if the data have been fully anonymized through removal of all identifiers associated with the data, including destruction of the key linking the subject’s data to his or her identity (Please see previous note on “anonymized” data).

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10.4 Decedent Data

While the Common Rule does not apply to decedents (and thus does not require IRB review), the Privacy Rule does apply. Specifically, the Privacy Rule requires researchers to provide written assurance that they will protect the privacy of decedents' identifiable health information. Important to remember is that the Privacy Rule does not distinguish between living and deceased subjects in terms of the requirement for tracking disclosures pursuant to a waiver of authorization. Therefore, tracking of disclosures of decedents' PHI will be required by the investigator. You may find the "UVMMC Attestation Form for Decedent Research (DOCX)" in the IRB forms page.

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11. Certificates of Confidentiality

Purpose

Certificates of Confidentiality (CoCs) protect the privacy of research subjects by prohibiting disclosure of identifiable, sensitive research information to anyone not connected to the research except when the subject consents or in a few other specific situations.

Scope

The NIH policy applies to all biomedical, behavioral, clinical, or other research funded wholly or in part by the NIH whether supported through grants, cooperative agreements, contracts, other transactions awards, or conducted by the NIH Intramural Research Program, that collects or uses identifiable, sensitive information.

The NIH will continue to consider request for CoCs for non-federally funded research in which identifiable, sensitive information is collected or used.

Any projects with CoCs issued in the past, regardless of funding sources, must comply with the requirements of the CoC policy, especially the new disclosure requirements and restrictions. 

  • The new disclosure requirements prohibit disclosure of the name of research subjects or any identifiable research information, document, or biospecimen to anyone not connected with the research except under very specific circumstances as detailed in the CoC policy.

Who Issues CoCs

Who issues CoCs depends upon who is funding the research.

Effective October 1, 2017, NIH will automatically issue CoCs to all research funded by NIH that is collecting or using identifiable, sensitive information. NIH funded researchers are automatically issued a CoC through their award. Separate documentation of the CoC will not be provided by NIH.

Several non-NIH HHS agencies, including CDC, FDA, HRSA, and SAMHSA, issue CoCs.

If your research is funded by a non-HHS Federal Agency other than HHS, you may request a CoC for a specific project that involves sensitive, identifiable information.

Health-related research that is not federally funded in which identifiable, sensitive information is collected or used, may request a Certificate of Confidentiality (CoC) for specific projects.

Extent and Limitations of Coverage

Disclosures are only permitted when:

  • Required by Federal, State, or local laws (e.g., as required by the Federal Food, Drug, and Cosmetic Act, or state laws requiring the reporting of communicable diseases to State and local health departments), excluding instances of disclosure in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding;
  • Necessary for the medical treatment of the individual to whom the information, document, or biospecimen pertains and made with the consent of such individual;
  • Made with the consent of the individual to whom the information, document, or biospecimen pertains; or
  • Made for the purposes of other scientific research that is in compliance with applicable Federal regulations governing the protection of human subjects in research.

Applying for a CoC when the Project is Not NIH Funded

If your research is funded by an HHS agency other than NIH, such as CDC, FDA, HRSA or SAMHSA or your research is funded by a non-HHS agency or the research is not federally funded, you still may request a CoC for specific health-related projects using sensitive, identifiable information, using the NIH online application system. Issuance of a CoC will be at the discretion of NIH.

Determine if a CoC is Appropriate

Research projects that collect personally identifiable, sensitive information and have been approved by the UVM/UVM Medical Center IRB are eligible for a CoC. Requesting sensitive information from a participant does not automatically make it eligible for a CoC.

Some research areas that are eligible for a CoC are:

  • Research on HIV, AIDS, and other STDs;
  • Studies that collect information on sexual attitudes, preferences, or practices;
  • Studies on the use of alcohol, drugs or other addictive products;
  • Studies that collect information on illegal conduct;
  • Studies that gather information that if released could be damaging to a participant’s financial standing, employability, or reputation within the community;
  • Research involving information that might lead to social stigmatization or discrimination if it were disclosed;
  • Research on participant’s psychological well-being or mental health;
  • Genetic studies, including those that collect and store biological samples for future use;
  • Research on behavioral interventions and epidemiologic studies.

Projects that are not eligible for a certificate are:

  • not research based;
  • not collecting sensitive information or information that, if released publicly, might harm the research participants,
  • not collecting personally identifiable information, or
  • not involving a subject matter that is within a mission area of the National Institutes of Health.

IRB Review

The protocol should include the fact that the study will have a CoC. If during its review of research for which an investigator has not identified the need for a CoC, the IRB may recommend applying for a CoC. The IRB does not allow participant recruitment until the CoC has been obtained and is on file with the IRB.

An application for a CoC is submitted after the IRB has approved the research project. This is because certificate issuance is conditioned upon IRB approval. Given this pre-requisite, the IRB will approve the protocol prior to CoC issuance; however, a written consent form would be released marked as, “For use only after a CoC is in place.” You must submit the CoC certificate to the IRB in order to receive the approved IRB stamped consent form for use.

The informed consent form must include a description of the protections and limitations of the CoC in the confidentiality section, including the circumstances in which the investigators plan to disclose voluntarily identifying information about research subjects (see Appendix N. Exceptions to Confidentiliaty)

Suggested Consent Language Describing the CoC Protections

This should be included within the Confidentiality Section of the consent form.

To help us protect your privacy, we have obtained a Certificate of Confidentiality from the National Institutes of Health. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, [except as explained below].

[Use the following language as applicable] The Certificate cannot be used to resist a demand for information from personnel of the United States federal or state government agency sponsoring the project and that will be used for auditing or program evaluation of agency funded projects or for information that must be disclosed in order to meet the requirements of the federal Food and Drug Administration (FDA). You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, medical care provider, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information.

[language such as the following should be included if researcher intend to make voluntary disclosure about information obtained in the research such as child abuse, or intent to hurt self or others.] The Certificate of Confidentiality will not be used to prevent disclosure to state or local authorities of [list what will be reported, such as child abuse and neglect, or harm to self or others].

Applying for a Certificate

Certificates are granted to institutions (not investigators nor IRBs), based upon an investigator’s application, for single, well-defined research project. Certificates are sometimes issued for cooperative multi-site projects which must have a coordinating center or lead institution. The coordinating center/lead institution can apply on behalf of all institutions associated with the multi-site project and must ensure that all participating institutions conform to the application assurances.

As part of the application, a Coc Assurance must be signed by the PI and UVM’s authorized institutional official. The UVM Board has delegated authority to the Executive Director for Research Administration. You may send the Assurance template in need of a signature to the Research Analyst with whom you are working. Assurance template is below and can be copied onto letterhead.

“Certificate of Confidentiality Assurance

This institution agrees to use the Certificate of Confidentiality to protect against the compelled disclosure of personally identifiable information and to support and defend the authority of the Certificate against legal challenges.

The institution and personnel involved in the conduct of the research will comply with the applicable Federal regulation for the protection of human subjects or, if no such Federal regulation is otherwise applicable, they will comply with 45 CFR Part 46.

This Certificate of Confidentiality will not be represented as an endorsement of the project by the DHHS or NIH or used to coerce individuals to participate in the research project.

All subjects will be informed that a Certificate has been issued, and they will be given a description of the protection provided by the Certificate.

Any research participant entering the project after expiration or termination of the Certificate will be informed that the protection afforded by the Certificate does not apply to them.

______________________________ ______________________________

Signature of Principal Investigator Printed Name of Principal Investigator

______________________________

Signature of Institutional Official

______________________________

Name and Title of Institutional Official

____________________________

____________________________

Address of Institutional Official”

 

NIH-Funded Research

If your NIH-funding will or has ended but the collection of new data from research participants will continue without NIH-funding you will need to apply for a CoC for continuity of protections using the CoC application system. If your NIH funding will or has ended but your study has completed all enrollment and data collection, there is no need to extend the Certificate. Sensitive, identifiable research information maintained by investigators during any time a Certificate is in effect, is protected permanently.

Certificate Expirations/Extensions

Certificates are not open-ended. They have an expiration date. If you determine that the research project will not be completed by the CoC expiration date, you must work with your NIH coordinator to submit a written request for an extension of the Certificate three (3) months prior to the expiration date.

NOTE: If your study has completed all enrollment and data collection, there is no need to extend the Certificate.  Sensitive, identifiable research information maintained by investigators during any time a Certificate is in effect, is protected permanently.

Amending a Certificate

If there is a SIGNIFICANT change in your non-NIH funded project after the Certificate has been issued, you should request an Amendment to your Certificate.  This includes such changes as a major change in the scientific scope of the project, changes in the PI, or in the drugs to be administered.  

Application Contacts

For a list of NIH IC Certificate Contacts, see the CoC Contacts at NIH and Other HHS Agencies that Issue Certificates. Some ICs use an online application process which is noted under the IC name on the Contacts List.

The Food and Drug Administration handles requests for Certificate of Confidentiality protection for studies that obtain an Investigational New Drug (IND) authorization or other FDA authorization. Projects with INDs or IDEs should apply to the FDA (Kevin Prohaska, D.O., M.P.H., Captain, U.S. Public Health Service Corps, Medical Officer, Division of Scientific Investigations, kevin.prohaska@fda.hhs.gov, 301-796-3707 OR Patricia Holobaugh, Bioresearch Monitoring Branch, HFM-664, Center for Biologics Evaluation and Research, patricia.holobaugh@fda.hhs.gov, 301-827-6347).

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12. Exceptions to Confidentiality Guidance

Mandatory Reporting

Vermont law requires health care providers and other professionals to take specific actions and to submit specified reports when certain facts or conditions become known to them (i.e. child abuse, elder abuse and imminent harm to self or others). These laws apply to the professional as a condition of their license or employment; and thus to any information gained by that person during the conduct of research.

The IRB expects that the PI will, when appropriate, communicate these potential exceptions to confidentiality to prospective research subjects during the informed consent process. This applies both to research projects specifically gathering such information and to projects where these circumstances or conditions may become known to the researcher even though the researcher does not directly seek this information (i.e. abuse of a child may be evident during a physical exam).

Do I need to include an Exceptions to Confidentiality section in my consent form?

If you are subject to mandatory reporting laws AND there is a reasonable possibility that you could discover information that would require you to break confidentiality then your consent form should include an Exceptions to Confidentiality section.

Am I (or any Key Personnel on this study) subject to mandatory reporting laws?

Health care workers, mental health providers, social workers, educators, members of the clergy, and law enforcement officers are examples of professionals who are mandated reporters in Vermont. Check with your professional licensing board if you are unsure if you are a mandated reporter. In addition, UVM requires any employee who has reasonable cause to believe that a minor participating in a program or activity at the University has been sexually abused or neglected to report the concern promptly to the Vermont Department for Children and Families (DCF).

What is the likelihood that in the course of carrying out my protocol I will discover information that requires mandatory reporting?

If the likelihood is low then the consent form does not need to include additional language. If during the conduct of the research a situation that required mandatory reporting arises, the PI should first and foremost act ethically to protect a potential victim (i.e. report suspected child abuse to the authorities). In addition the PI should report this to the IRB as the breach of confidentiality would be an Unanticipated Problem.

If there is a reasonable possibility, this should be disclosed as an exception to confidentiality to the potential participant during the informed consent process.

Suggested Consent Language

Place this consent language in the confidentiality section of the consent.

There is one exception to confidentiality that you should know about. By law, it is our responsibility to report to the appropriate authority suspicion of harm to children or to others.

If appropriate add: However, we are not seeking this type of information in our study nor will you be asked questions about these issues.

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13. Cooperative Research (Single IRB) (Sec. __.114)

The definition of cooperative research is any research project that involves more than one institution.

NIH Policy

As of January 25, 2018, NIH policy requires that all NIH multi-site protocols use a single IRB of record. Institutional Officials have decided that UVM will subcontract with Western IRB (WIRB) for single IRB services where UVM researchers wish to be the lead single IRB for their NIH proposals. Proposals should include the use of WIRB as the IRB of record for the multi-site research activities and budgets must be developed to include the expense for the use of this commercial IRB.

If UVM is not the lead site, they can participate and rely on another IRB for review, with appropriate reliance agreements in place. See Relying on External IRB for NIH Research guidance.

At this time, UVM IRB will not act as a lead single IRB nor will it rely on external IRBs for any non-NIH funded projects as there are insufficient resources. This will be revisited as soon as possible after successful implementation of the NIH requirement as described above.

Single IRB for non-NIH Funded Projects (New! Do not reference until the 2018 revised Common Rule takes effect)

The final rule will require under Sec. __.114 that any institution located in the United States that is engaged in cooperative research shall rely on approval by a single IRB for that portion of the research that is conducted in the United States. The compliance date for this is January 20, 2020. This change applies to all research regardless of funding.

This policy has two exceptions (detailed in Sec. __.114(b)(2)):

(1) Cooperative research for which more than single IRB review is required by law (including tribal law passed by the official governing body of a American Indian or Alaska Native tribe); and

(2) research for which any federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular study.

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13.1 SMART IRB

“SMART IRB, the Streamlined, Multisite, Accelerated Resources for Trials IRB Reliance platform, is a platform designed to ease common challenges associated with initiating multisite research and to provide a roadmap for institutions to implement the NIH Single IRB Review policy (effective date: January 25, 2018). Freely available for institutions and investigators, SMART IRB is an integrated, comprehensive platform that allows flexibility in the size and scope of collaboration to enable IRB reliance for multisite studies across the nation, regardless of funding status.”

There are currently 416 participating institutions who have joined the SMART IRB. The University of Vermont and the University of Vermont Medical Center have been participants in the SMART IRB platform since last summer. This means that we have signed onto the SMART IRB Agreement. This agreement clearly defines the roles and responsibilities of each party and eliminates the need to sign individual agreements for each study in which you plan to collaborate. Investigators can also use the SMART Online Reliance System to request, track and document reliance agreements. To learn more about SMART IRB go their website at https://smartirb.org/.

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13.2 Collaborative Agreements

Data Use Agreement

When a researchers wants to transfer human subject data to another researcher or company, whether non-profit or commercial, having an advance agreement is necessary. The goal is to prevent misunderstandings about who has which rights to do what to/with the material, to address liability for flaws or problems that may occur, and to make sure you can publish under academic freedom. The most common way to do this is via a data use agreement (DUA).

Researchers who intend to share human subject data outside of the institution must contact Sponsored Project Administration for further information regarding negotiation of a Data Use Agreement.

Independent Investigator Agreement (IIA)

A formal, written, binding agreement in which UVM agrees to serve as the IRB for another institution or individual, when the other institution or individual either has no IRB or the IRB is not federally registered. The IIA sets out terms and conditions for the institutions. UVM does not currently enter into IIAs with other institutions or individuals.

Institutional Support Letter (e.g., schools, nursing homes)

A letter signed by an executive director, chief executive officer, board president or other individual with authority to commit the institution’s resources, acknowledging the proposed research activity, and granting permission for the engagement of their employee and facilities (if applicable) in that activity. A template of our support letter is located in our forms page.

Reliance Agreement

A reliance agreement (also called an IRB Authorization Agreement) is a document signed by two or more institutions engaged in human subjects research that permit one or more institutions to cede review to another IRB. The signed agreement permits a single IRB to review human subject research activities for more than one site. At this time UVM is only entering into Reliance Agreements where a UVM PI is engaged in a cooperative research project that is funded by NIH.

Material Transfer Agreement

If a researcher wishes to share biological materials collected at the University of Vermont/UVMMC with colleagues at another institution, the human biological materials must be transferred pursuant to a University Material Transfer Agreement (MTA) executed by the Office of Technology Commercialization.

Memorandum of Understanding (MOU)

Researchers often collaborate and share research tools with other scientists or institutions without receiving funding.  For many of these collaborations, a written agreement is beneficial or necessary. These agreements set out expectations, terms, and requirements that protect the interests of the investigators and the participating organizations. UVM investigators proposing to include an outside entity in their research should review Sponsored Project Administration’s Agreement page for further information regarding negotiation of a MOU.

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13.3 Procedures for Relying on External IRB for NIH Research (Sec __.114(b)(1))

At this time, the University of Vermont (UVM) will allow UVM researchers to use an External IRB for multicenter, domestic human subjects protocols where the project has NIH funding. Currently, UVM has the following reliance agreements in place to meet the NIH requirement.
  • National Cancer Institute Central IRB (NCI CIRB) – adult and pediatric oncology protocols
  • StrokeNet – StrokeNet protocols
  • Western IRB (WIRB) – when UVM Lead Investigator wishes to subcontract single IRB

Reliance agreements with other institutions for NIH funded research will be considered following the steps outlined below.

Cooperative research protocols where there is no NIH funding, will continue to be reviewed by the UVM IRB.

Responsibilities

The External IRB will be responsible for Committee review and ensuring that the protocol meets the regulatory requirements for protecting human subjects. The University of Vermont and the University of Vermont Medical Center (UVMMC) are responsible for oversight of human subject protections. Each of the following roles play an important part in protecting human subjects.

Roles

Institutions

UVM and UVMMC are responsible for the following, regardless of which IRB reviews the research:

  • Education and training of investigators & research staff
  • Policies and procedures for the conduct of research
  • Conflict of Interest review
  • Appropriate institutional agreements

IRB

The role of an IRB is to review protocols to ensure that adequate human subject protections are in place. Protocol review can be the responsibility of the UVM IRB or an External IRB.

UVM/UVMMC Principal Investigator

UVM PIs have the overall responsibility for the conduct of the protocol and must adhere to the policies and procedures of both the External IRB and the UVM IRB.

Designated Contact Person

The UVM/UVMMC PI needs to identify one person on their research staff as their designated contact for all interactions and communications with the External IRB. This person will work as the liaison between the External IRB and the local PI as well as the intermediary between the External IRB and UVM’s IRB.

Others

  • UVM PIs who will conduct protocols utilizing UVMMC resources will work with the UVMMC Compliance Office to create a billing plan.
  • UVM Office of General Counsel will be involved with reliance agreement negotiations as necessary.
  • HIPAA issues may arise which would involve the UVMMC Privacy Specialist.
  • Institutional Committees
  • Other departments or individuals may need to be consulted.

Steps to Allow Reliance on an External IRB

1. Request to Allow Reliance on an External IRB

For NIH Research: PIs must complete and submit electronically to UVM IRB a File Request to Rely on an External IRB form (DOCX) (UVM PI may need to contact the external IRB for answers to questions 2 – 5 on the form). Submission of this form and its required attachments begins a record in UVM’s electronic system. To help us determine the level of local oversight that may be required for this protocol, the UVM IRB requires that you submit the following additional materials for review:

  • a copy of the human subject protocol;
  • the sponsor provided consent template(s);
  • roster of key personnel working on the protocol;
  • any reliance agreements that require institutional signature;
  • and a Data Management and Security Plan.

The latter is a UVM-specific form and addresses data collection, storage and sharing. This information helps to determine if data use agreements are necessary.

Note: It is very important that you receive approval from your department chair, required applicable institutional committees as well as be in contact with any ancillary departments that are included or impacted by your participation in the research project. (e.g., Radiation Safety Committee, Institutional Biosafety Committee, Scientific Advisory Committee, Investigational Pharmacy).

Research projects that utilize any UVMMC resources are required to have a coverage analysis and billing plan conducted by UVMMC Billing Compliance, so you should contact that office early in the process.

2. Meeting with UVM IRB Staff

Before submitting protocol/consent materials to an External IRB for review the PI and his/her designated contact are required to meet with IRB staff. This meeting is to review:

  • the Single IRB process;
  • your responsibilities as the UVM PI;
  • your responsibilities to the external IRB;
  • what resources you may need;
  • an appropriate consent/HIPAA document;
  • our expectations for continued submissions and communications (adverse events, UAPs, noncompliance, key personnel changes, protocol changes that affect the required language in the consent form); and
  • the status of the agreement.

We will review an exit interview document together and the PI will be provided with a signed copy to document UVM IRB’s approval to move forward with reliance on an external IRB. Completion of this step does not mean that you may begin protocol activities. Allowance to begin protocol activities at UVM/UVMMC will not occur until you have reached step 5 in this process.

3. Develop Materials for External IRB Submission

  • UVM designated contact is responsible for communicating with the External IRB to determine what documents are needed for review and the procedures for submission.
  • UVM designated contact will develop the local consent to include the local UVM required consent and HIPAA language.

4. Once UVM PI Obtains External IRB Approval

Prior to the start of any research activities at UVM, the UVM PI must complete and submit electronically, the File Notification of Approval from the External Single IRB form (DOCX) to the UVM IRB. Include the following materials in the submission:

  • External IRB approval letter;
  • Final approved protocol;
  • Final approved local consent form;
  • Additionally, if there have been any changes to your key personnel roster or the original Data Management and Security Plan.

The PI may not begin protocol activities until he/she receives notification from the UVM IRB that they have met the local requirements and are allowed to begin the protocol.

5. Allowance to Begin Research Activities Locally

The UVM IRB will review the materials, as listed above, to ensure that all local requirements are met, for example, UVMMC has completed a Coverage Analysis and Billing Plan if applicable, the final consent includes the required language, agreements are in place, etc. Once it has been determined that all issues are addressed, an Allowance to Begin Research Activities Reviewed by an External IRB memo will be forwarded to the UVM PI.

UVM IRB Ongoing Submission Requirements

Changes in PI or Key Personnel

UVM PI or designated contact must submit any changes to the protocol PI or key personnel. UVM is required to know who is assigned as the PI, as well as to ensure key personnel have completed required human subjects training prior to working on the protocol. Use electronic form to update personnel.

Unanticipated Problems

UVM PI or designated contact must submit local adverse events or unanticipated problems meeting the UVM IRB reporting criteria. Complete the UVM IRB Unanticipated Problem … form and submit through the electronic system.

Closure of Protocol

UVM PI or designated contact must submit a notice of protocol closure. Submit sponsor closure correspondence through the electronic system.

Non-Compliance Issues

UVM PI or designated contact must submit allegations of non-compliance meeting the UVM reporting criteria. Complete the UVM IRB Unanticipated Problem … form and submit through the electronic system.

Protocol changes which affect required consent language

Protocol changes that affect our required consent language must be submitted to the UVM IRB for review, prior to implementation. Submit electronically the sponsor correspondence regarding the protocol change along with revised local consent form for review and prior UVM IRB approval.

Ongoing Monitoring

Dependent upon the complexity and risk level of the protocol, the UVM IRB may develop a formal monitoring plan. This will be determined at Step 5 above and communicated through the Allowance to Begin Research Activities Reviewed by an External IRB memo.

The External IRB may request that the UVM IRB conduct an investigation of any compliance-related issues that they discover.

Serious/Continuing Noncompliance Review Process

UVM IRB will investigate issues of serious or continuing non-compliance independent of the External IRB, following the Noncompliance Policy and Procedures guidance. It is possible that the External IRB may investigate separately or the investigative process may be shared between the two IRBs.

The External IRB is responsible for reporting to applicable regulators and sponsors. The UVM IRB will report to the Institutional Officials and Department Chair.

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13.4 Procedures for Reliance on National Cancer Institute, Central Institutional Review Boards - Adult

The University of Vermont (UVM), in cooperation with The University of Vermont Cancer Center (UVM Cancer Center/UVMCC), has entered into an agreement with the NCI CIRB (CIRB) whereby UVM may rely upon CIRB for IRB review and approval of CIRB-designated protocols.

Roles and Responsibilities

CIRB - The CIRB performs initial, amendment and continuing review of the study and any other study-specific documents submitted by the Study Chair to the CIRB. The CIRB conducts review of local context considerations in accordance with the information provided in the “Annual Signatory Institution Worksheet about Local Context”, “Annual Principal Investigator Worksheet about Local Context” and “Study-Specific Worksheet about Local Context”. The CIRB reviews unanticipated problems and potentially serious/continuing noncompliance. It serves as the single IRB of record for eligible, approved studies. CIRB-approved materials are hosted on a dedicated website to which UVM Cancer Center and UVM IRB staff have access.

University of Vermont Cancer Center - UVMCC oversees the initial and ongoing protocol selection through its Transdisciplinary Disease Team (TDT) and Protocol Review and Monitoring Committee (PRMC). These reviews are focused on resource utilization and local feasibility. UVMCC is also responsible for monitoring the conduct of cancer-related research.

University of Vermont Cancer Center Clinical Trials Office (UVM Cancer Center CTO or UVMCC CTO) - The UVMCC CTO incorporates the NCI CIRB-approved boilerplate language into the CIRB-approved model consent form to create the local consent form, following acceptance by the CIRB of the “Study Specific Worksheet.” The UVMCC CTO reviews and documents the accuracy and completeness of local consent forms and HIPAA authorizations, then stamps the form(s) with the approval date prior to release for use.

University of Vermont Cancer Center Data and Safety Monitoring Committee (UVM Cancer Center DSMC or UVMCC DSMC) – The UVMCC DSMC reviews all reported unanticipated problems and potential serious non-compliance for all cancer related research approved by the UVMCC PRMC. The DSMC also oversees the monitoring of protocol compliance.

University of Vermont IRB (UVM IRB) – While the UVM IRB no longer manages the review for these studies, it continues to have some responsibilities during the conduct of the research. The office responsible for the administration and staffing of the University of Vermont IRB is the Research Protections Office (RPO). Among its responsibilities, the UVM IRB ensures compliance with their responsibilities under the terms of the Federalwide Assurances (FWA’s) and with the responsibilities outlined in the “Authorization Agreement/Division of Responsibilities Between the NCI Central Institutional Review Board and the Signatory Institution”. The IRB tracks key personnel training at the University of Vermont, the University of Vermont Medical Center (UVM Medical Center/UVMMC) and affiliated sites. In the event of an unanticipated problem or potential serious non-compliance, the UVM IRB investigates and manages the situation and provides notification to the CIRB, including a plan to manage the situation and measures to prevent similar occurrences. The UVM IRB also submits the “Annual Signatory Institution Worksheet about Local Context.”

Individual Principal Investigators - The Principal Investigator (PI) submits the “Annual Principal Investigator Worksheet about Local Context” and the “Study-Specific Worksheet about Local Context.” Unless otherwise noted, the PI or designee submit the required local forms outlined in this document. The PI’s general responsibilities related to the overall oversight of research conducted in his/her name are outlined on the 1572 submitted as part of his/her annual investigator registration to the NCI. The PI must adhere to all CIRB policies and procedures, applicable UVM IRB policies and procedures, and all applicable federal, state and local laws and regulations regarding the protection of human subjects in research.

UVM Medical Center Integrity and Compliance – The UVM Medical Center Integrity and Compliance approves the required billing plans for these protocols.

Process to Participate in a NCI CIRB Approved Protocol

Step 1.

The PI submits a NCTN protocol, and model consent form to the UVMCC TDT for committee review and endorsement of study participation. The TDT will decide if the study moves forward based on scientific merit, alignment with the strategic goals of the UVMCC, and other considerations (e.g. affiliate site interest).

Step 2.

The completed TDT form is submitted to the UVMCC CTO leadership for feasibility review, which includes a pre-review by UVMMC Integrity and Compliance. This will allow for any costs not billable to patient insurance or not covered by the study to be identified up front. The PI or designee will be informed of those potential costs by the UVMCC CTO and alternative funding must be identified prior to approval from the UVMCC CTO..

Step 3.

The PI or designee confirms that the proposed study is on the CIRB menu via www.ncicirb.org or https://www.ctsu.org. The PI or designee confirms that the “Annual Principal Investigator Worksheet About Local Context” and “Annual Signatory Institution Worksheet about Local Context” are current and approved by the CIRB.

Step 4.

The PI or designee downloads the NCTN protocol andcompletes the required forms for PRMC review.

Step 5.

Once Steps 1-4 are completed and permission is obtained from the TDT, the PI or designee submits the required forms to the PRMC. The PRMC conducts its review for utilization and prioritization of UVMCC resources.

Step 6.

Following approval by the PRMC, the PI or designee submits the completed “Study-Specific Worksheet About Local Context” via IRB Manager at https://irbmanager.becirb.com.

Step 7.

The PI or designee submits the CIRB Cover form to the UVM IRB. The UVM IRB will enter minimal protocol data into InfoEd for tracking and reporting purposes.

Step 8.

The CIRB reviews and approves the “Study-Specific Worksheet About Local Context.” Following acceptance by the CIRB, the UVMCC CTO will use a standard checklist to conduct a final content review and approval of the consent form(s), placing a stamp of approval on the approved version(s) . The UVMCC CTO also notifies the UVM IRB of the final approval.

Ongoing Institutional Responsibilities

Key Personnel Changes

  • Change in PI
    • CIRB – PI submits “Study Specific Worksheet” to CIRB
    • PRMC – PI or delegate submits “Request for Change in Principal Investigator” to PRMC
    • UVM IRB – PI or designee submits “Request for Change in Principal Investigator” to the UVM IRB
  • Key personnel
    • CIRB – Primary contact submits “Add or Remove Institution Personnel” form to the CIRB
    • PRMC - no submission is required
    • UVM IRB – PI or designee updates the Master Key Personnel lists by submitting the “Request for Change in Key Personnel” to the UVM IRB

Amendments

  • CIRB-generated amendments affecting the use of UVM Cancer Center resources and/or funding for the study
    • PRMC – PI or designee submits a “Request for Amendment” to PRMC
    • UVMMC Integrity and Compliance – PI or designee submits updated protocol, consent and/or funding information to UVMMC Integrity and Compliance
  • CIRB-generated amendments affecting the consent form(s)
    • PRMC – no action required unless amendment significantly impacts the scientific justification for the study, then the PI or designee must submit the updated documents to PRMC for review
    • UVM IRB – no submission is required
    • UVMCC CTO – PI or designee submits revised consent form(s) with local boilerplate language incorporated, to UVMCC CTO representative for review and approval

Safety/Non-compliance

  • Local Adverse events (not serious)
    • CIRB – Coordinator includes this information in the NCTN data submission to the CIRB
    • PRMC – no submission is required
    • UVM IRB – no submission is required
  • Broadcast Safety Reports
    • PIs review and sign per the appropriate cooperative group policy. No further reporting or action is required.
    • PRMC – no submission is required
    • UVM IRB – no submission is required
  • Unanticipated problems (including local SAEs) potentially involving risk to subjects or others
    • CIRB – PI submits the “Unanticipated Problem and/or Noncompliance” form to the CIRB
    • PRMC – no submission is required
    • UVMCC DSMC – PI or delegate submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” form to the UVMCC DSMC
    • UVM IRB - PI or delegate submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” form to the UVM IRB
  • Potentially serious/continuing non-compliance
    • CIRB – PI submits the “Unanticipated Problem and/or Noncompliance” form to the CIRB
    • UVMCC DSMC – PI or designee submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” to the UVMCC DSMC
    • UVM IRB – PI or designee submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” to the UVM IRB
  • Closure (by CIRB or UVMCC)
    • CIRB – UVMCC will notify CIRB only in the event of local closure, otherwise no action is required.
    • PRMC – PI or designee submits the CIRB Closure form, regardless of closure type, to the PRMC
    • UVM IRB – PI or designee submits the CIRB Closure form, regardless of closure type, to the UVM IRB

Special Situations

  • Non-English Speaking Individuals

UVM will follow the current policy and procedures for non-English speaking individuals found in Section 9.4of the IRB Policies and Procedures, Informed Consent and HIPAA Authorization Process for Non-English Speaking Individuals

  • Cognitively Impaired Individuals

UVM will follow the current policy and procedures for cognitively impaired individuals found in section 9.2. of the IRB Policies and Procedures, Surrogate Consent for Research (Legally Authorized Representatives).

  • Illiterate Individuals

The UVM IRB boilerplate consent language includes the statement below. Illiterate subjects will only make a mark or sign after having the consent read to and discussed with them, and they agree to participate.

Statement of Consent

You have been given and have read or have had read to you a summary of this research study. Should you have any further questions about the research, you may contact the person conducting the study at the address and telephone number given below. Your participation is voluntary and you may refuse to participate or withdraw at any time without penalty or prejudice to your present and/or future care.

  • Individuals Who Become Incarcerated

The CIRB is not constituted to review prisoner research. If a subject becomes incarcerated, and it is determined that he/she should remain on study, the UVM IRB will review and approve, if appropriate, to allow ongoing treatment.

  • Individuals who Become Pregnant

An unexpected pregnancy during protocol treatment would be considered an unanticipated event and would need to be reported as such to the CIRB, UVMCC DSMC, and the UVM IRB.

Ongoing Monitoring

The UVM Cancer Center monitors the conduct of cancer-related research through the UVMCC CTO Quality Assurance Program. All studies open to accrual under the purview of the CIRB will have a yearly administrative audit at the time of continuing review to confirm the following:

  • The most current informed consent forms are being used
  • The most current CIRB-approved boilerplate language is appropriately incorporated into the model-consent forms

Continuing/Serious Noncompliance Review Process

UVM, through the UVM IRB and in coordination with the UVM CC, will follow the NCI CIRB procedures for reporting continuing and serious noncompliance, in accordance with Section 10.0 of the CIRB SOPsand, applicable UVM IRB requirements, including any necessary local reporting to institutional officials. If UVM IRB review of local issues is required, it will be conducted under the UVM IRB’s operating procedures and will be coordinated with the NCI CIRB. The UVM IRB will comply with the NCI CIRB reporting requirements.

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13.5 Procedures for Reliance on National Cancer Institute, Central Institutional Review Boards - Pediatric

The University of Vermont (UVM), in cooperation with The University of Vermont Cancer Center (UVM Cancer Center/UVMCC), has entered into an agreement with the NCI CIRB (CIRB) whereby UVM may rely upon CIRB for IRB review and approval of CIRB-designated protocols.

Roles and Responsibilities

CIRB - The CIRB performs initial, amendment and continuing review of the study and any other study-specific documents submitted by the Study Chair to the CIRB. The CIRB conducts review of local context considerations in accordance with the information provided in the “Annual Signatory Institution Worksheet about Local Context”, “Annual Principal Investigator Worksheet about Local Context” and “Study-Specific Worksheet about Local Context”. The CIRB reviews unanticipated problems and potentially serious/continuing noncompliance. It serves as the single IRB of record for eligible, approved studies. CIRB-approved materials are hosted on a dedicated website to which UVM Cancer Center and UVM IRB staff have access.

University of Vermont Office of Clinical Trials Research (OCTR) – The OCTR oversees the initial and ongoing protocol selection through its Transdisciplinary Disease Team (TDT) and Protocol Review and Monitoring Committee (PRMC). These reviews are focused on resource utilization and local feasibility. UVMCC is also responsible for monitoring the conduct of cancer-related research.

University of Vermont Office of Clinical Trials Research (OCTR) - The OCTR incorporates the NCI CIRB-approved boilerplate language into the CIRB-approved model consent form to create the local consent form, following acceptance by the CIRB of the “Study Specific Worksheet.” The OCTR also has the delegated authority to review and approve HIPAA content for those same studies. The OCTR reviews and documents the accuracy and completeness of local consent forms/HIPAA content, then stamps the form with the approval date prior to release for use.

University of Vermont Cancer Center Data and Safety Monitoring Committee (UVM Cancer Center DSMC or UVMCC DSMC) – The UVMCC DSMC reviews all reported unanticipated problems and potential serious non-compliance for all cancer related research approved by the UVMCC PRMC. The DSMC also oversees the monitoring of protocol compliance.

University of Vermont IRB (UVM IRB) - While the UVM IRB no longer manages the review for these studies, it continues to have overall responsibility for the conduct of the research. Among its responsibilities, the UVM IRB ensures the safe and appropriate performance of the research at the University of Vermont Medical Center (UVM Medical Center/UVMMC) and affiliated sites and tracks key personnel training. In the event of an unanticipated problem or potential serious non-compliance, the UVM IRB investigates and manages the situation and provides notification to the CIRB, including a plan to manage the situation and measures to prevent similar occurrences. The UVM IRB also submits the “Annual Signatory Institution Worksheet about Local Context.”

Individual Principal Investigators - The Principal Investigator (PI) submits the “Annual Principal Investigator Worksheet about Local Context” and the “Study-Specific Worksheet about Local Context.” Unless otherwise noted, the PI or designee submit the required local forms outlined in this document. The PI’s general responsibilities related to the overall oversight of research conducted in his/her name are outlined on the 1572 submitted as part of his/her annual investigator registration to the NCI. The PI must adhere to all CIRB policies and procedures, applicable UVM IRB policies and procedures, and all applicable federal, state and local laws and regulations regarding the protection of human subjects in research.

UVM Medical Center Integrity and Compliance – The UVM Medical Center Integrity and Compliance approves the required billing plans for these protocols.

Process to Participate in a NCI CIRB Approved Protocol

Step 1.

The PI or designee confirms that the proposed study is on the CIRB menu via www.ncicirb.org or https://www.ctsu.org. The PI or designee confirms that the “Annual Principal Investigator Worksheet About Local Context” and “Annual Signatory Institution Worksheet about Local Context” are current and approved by the CIRB.

Step 2.

The PI or designee downloads the cooperative group protocol, completes the CIRB Cover form, develops the consent/HIPAA forms,.

Step 3.

The PI submits a cooperative group protocol, and model consent form to the UVMCC TDT for committee review and endorsement of study participation. The TDT will decide if the study moves forward based on scientific merit, alignment with the strategic goals of the UVMCC, and other considerations (e.g. affiliate site interest).

Step 4.

Once Steps 1-3 are completed and permission is obtained from the TDT, the PI or designee submits the CIRB Cover form, cooperative group protocol, consent/HIPAA form, and Protocol Checklist form to the PRMC. The PRMC conducts its review for utilization and prioritization of UVMCC resources. PI or designee must send completed, signed Coverage and Analysis Budget form to Compliance.

Step 5.

At the time of submission to the CIRB & PRMC the responsible study coordinator will submit protocol related materials including the COG Supplemental Funding Memo (if applicable) to UVM Medical Center Integrity and Compliance for review and development of the study specific billing plan. UVM Medical Center Integrity and Compliance staff will send the proposed billing plan to the PI and responsible clinical research coordinator for review and confirmation of approval if it is correct. This will allow for any costs not billable to patient insurance or not covered by the study to be identified up front.

Step 6.

Following approval by the PRMC, the PI or designee submits the completed “Study-Specific Worksheet About Local Context” via IRB Manager at https://irbmanager.becirb.com.

Step 7.

The CIRB reviews and approves the “Study-Specific Worksheet About Local Context.” Following acceptance by the CIRB, OCTR staff will use a standard checklist to conduct a final content review for approval of the consent/HIPAA form, placing a stamp of approval on the form. The OCTR also notifies the UVM IRB of the final approval by submitting the completed UVM CIRB Cover Form which includes the CIRB approval. The OCTR/ Pediatric Oncology will not move forward with enrolling participants until the protocol is approved by CIRB and a billing plan has been approved by UVM Medical Center Integrity and Compliance.

Step 8.

The PI or designee submits the CIRB Cover form and a copy of the CIRB approval to the UVM IRB. The UVM IRB will enter minimal protocol data into InfoEd for tracking and reporting purposes.

Ongoing Institutional Responsibilities

Key Personnel Changes

  • Change in PI
    • CIRB – PI submits “Study Specific Worksheet” to CIRB
    • PRMC – PI or delegate submits “Request for Change in Principal Investigator” to PRMC
    • UVM IRB – PI or designee submits “Request for Change in Principal Investigator” to the UVM IRB – this information will be reflected in the monthly “All Active Protocols” report.
  • Change in key personnel
    • CIRB – Primary contact submits “Add or Remove Institution Personnel” form to the CIRB
    • PRMC - no submission is required
    • UVM IRB – PI or designee updates the Master Key Personnel lists by submitting the “Request for Change in Key Personnel” to the UVM IRB

Amendments

  • Cooperative Group-generated amendments affecting the use of UVM Cancer Center resources/or funding/or approved billing plan for the study
    • PRMC – PI or designee submits a “Request for Amendment” to PRMC
    • UVM IRB – no submission is required
    • UVMMC Integrity and Compliance – PI or designee submits updated protocol, consent and/or funding information to UVMMC Integrity and Compliance
  • Cooperative Group-generated amendments (affecting/not affecting the consent/HIPAA form)
    • PRMC – no action required unless amendment significantly impacts the scientific justification for the study, then the PI or designee must submit the updated documents to PRMC for review
    • UVM IRB – no submission is required
    • OCTR – PI or designee submits revised consent/HIPAA form, with local boilerplate language incorporated, to OCTR representative - if applicable

Safety/Non-compliance

  • Local Adverse events (not serious)
    • CIRB – Coordinator includes this information in the cooperative group data submission to the CIRB
    • PRMC – no submission is required
    • UVM IRB – no submission is required
  • Broadcast SAEs
    • PIs review and sign per the appropriate cooperative group policy. No further reporting or action is required.
    • PRMC – no submission is required
    • UVM IRB – no submission is required
  • Unanticipated problems (including local SAEs) potentially involving risk to subjects or others
    • CIRB – PI submits the “Unanticipated Problem and/or Noncompliance” form to the CIRB
    • PRMC – no submission is required
    • UVMCC DSMC – PI or delegate submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” form to the UVMCC DSMC
    • UVM IRB - PI or delegate submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” form to the UVM IRB
    • UVM Medical Center - SAFE report (if applicable)
  • Potentially serious/continuing non-compliance
    • CIRB – PI submits the “Unanticipated Problem and/or Noncompliance” form to the CIRB
    • UVMCC DSMC – PI or designee submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” to the UVMCC DSMC
    • UVM IRB – PI or designee submits the “Unanticipated Problem Potentially Affecting Risk to Subjects or Others” to the UVM IRB

Closure (by CIRB or UVMCC)

    • CIRB – OCTR will notify CIRB only in the event of local closure, otherwise no action is required.
    • PRMC – PI or designee submits the CIRB Closure form, regardless of closure type, to the PRMC
    • UVM IRB – PI or designee submits the CIRB Closure form, regardless of closure type, to the UVM IRB

Special Situations

  • Non-English Speaking Individuals

UVM will follow the current policy and procedures for non-English speaking individuals found in Section 9.4 of the Manual for Human Subjects Research, Informed Consent and HIPAA Authorization Process for Non-English Speaking Individuals. As per UVM IRB Manual for Human Subjects Research short forms and long forms (as appropriate) will be submitted for review and approval to CIRB with documentation of the certificate of accuracy. Once the document is approved by CIRB it will be made available to the participant/ participant’s legal guardian in native language of the participant/ participant’s legal guardian for the purpose of obtaining consent for participation.

  • Cognitively Impaired Individuals

UVM will follow the current policy and procedures for cognitively impaired individuals found in section 9.2 of the IRB Policies and Procedures, Surrogate Consent for Research (Legally Authorized Representatives).

  • Illiterate Individuals

The UVM IRB boilerplate consent language includes the statement below. Illiterate subjects will only make a mark or sign after having the consent read to and discussed with them, and they agree to participate.

Statement of Consent

You have been given and have read or have had read to you a summary of this research study. Should you have any further questions about the research, you may contact the person conducting the study at the address and telephone number given below. Your participation is voluntary and you may refuse to participate or withdraw at any time without penalty or prejudice to your present and/or future care.

  • Individuals Who Become Incarcerated

The CIRB is not constituted to review prisoner research. If a subject becomes incarcerated, UVM will follow the current policy and procedures for individuals who become incarcerated found in section 11.C. of the Manual for Human Subjects Research, Prisoners.

  • Individuals who Become Pregnant

An unexpected pregnancy during protocol treatment would be considered an unanticipated event and would need to be reported as such to the CIRB, UVMCC DSMC, and the UVM IRB.

Ongoing Monitoring

The UVM Cancer Center monitors the conduct of cancer-related research through the UVMCC CRU Quality Assurance Program. All COG studies open to enrollment at UVM that are under the purview of the CIRB will have a yearly administrative audit at the time of continuing review by OCTR staff to confirm the following:

  • The most current informed consent forms/HIPAA forms are being used
  • The most current CIRB-approved boilerplate language is appropriately incorporated into the model-consent forms

Continuing/Serious Noncompliance Review Process

UVM, through the UVM IRB and in coordination with the UVM CC, will follow the NCI CIRB procedures for reporting continuing and serious noncompliance, in accordance with Section 10.0 of the CIRB SOPs and, appropriate UVM IRB requirements, including any necessary local institutional reporting. If UVM IRB review of local issues is required, it will be conducted under the UVM IRB’s operating procedures and will be coordinated with the NCI CIRB. The UVM IRB will comply with the NCI CIRB reporting requirements.

Forms

CIRB (available to OCTR staff)

  • Annual Principal Investigator Worksheet About Local Context
  • Unanticipated Problem and/or Noncompliance
  • Study-Specific Worksheet About Local Context
  • Study Closure or Transfer of Study Review Responsibilities
  • Requesting an Assent Waiver Worksheet

Local Submission Forms (available through OCTR staff)

  • CIRB Protocol Cover form
  • CIRB Consent Checklist – Pediatric Oncology Specific
  • Protocol Checklist form – Pediatric Oncology Specific
  • PRMC Protocol Check List (which includes Modality Sign-off and TDT approval)
  • CIRB Protocol Closure form

UVM IRB (available on IRB forms page)

  • Request for Change in Key Personnel
  • Unanticipated Problem Potentially Affecting Risk to Subjects or Others

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13.6. Procedures for Reliance on Western IRB for NIH Projects

As of January 25, 2018, NIH policy (opens in a new window) requires that all NIH multi-site protocols use a single IRB of record. Institutional Officials have decided that UVM will subcontract with Western IRB (WIRB) (opens in a new window) for single IRB services where UVM researchers wish to be the lead single IRB for their NIH proposals. Proposals should include the use of WIRB as the IRB of record for the multi-site research activities and budgets must be developed to include the expense for the use of this commercial IRB.

Reference the Western IRB web page for Step-by-Step instructions.

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14. Funding/Contracts/Fees

RPO, SPA and the Office of Clinical Trials Research work together to ensure all institutional and sponsor approvals and contracts are in place prior to the initiation of sponsored research involving human subjects.

The IRB is required to ensure that all research described in a grant application or proposal is entirely consistent with any corresponding protocol(s) reviewed and approved by the IRB. Any discrepancies must be resolved prior to the start of the project. The IRB works with SPA and the Office for Clinical Trials Research to establish that an appropriate connection is made between the application and the protocol being reviewed.

Relevant information regarding sponsored projects is shared between Offices (e.g. conflict of interest, study incentives, key personnel). Protocol approvals are not released until applicable contracts or agreements have been fully executed.

 

14.1 When the Project is a New Competing or a Competing Renewal Application and the New Protocol is Identical or Substantially Similar to an Approved Protocol

Obtaining grant funding is extremely competitive. The same grant proposal may be submitted to multiple funding agencies at once or the same agency at different time points. If you obtain new funding, it is your responsibility to submit the corresponding grant and protocol for IRB review and approval.

The IRB treats identical protocols as new applications, however, a new committee review may not be required if the project is the same or substantially similar to the previously approved protocol.

If this is the case, you must submit the following:

1. One copy of your new grant application and any corresponding protocol.

2. One copy of an updated Common Protocol Cover Form.

3. One copy of a Request for Waiver of Consent/Authorization (if applicable).

4. A copy of the Consent Form(s).

5. A letter to the committee chair explaining that you are submitting a similar grant application to a different funding agency. State that this new protocol application is identical to the old one (provide CHRBSS/CHRMS file #) with regard to hypotheses, specific aims, and human subject involvement (or describe minor differences).

If this application is essentially the same as the previously approved application with only minor differences clearly described in a letter, the protocol will receive administrative review. If substantial changes are proposed, then a new committee review may be required.

Competing Resubmissions or Supplements

Grant resubmissions require an amendment to a previously approved protocol if it is identical or substantially similar to that protocol and grant. The amendment form and a copy of the resubmitted grant application are to be submitted for review and approval. Administrative and competitive supplements also require an amendment to a previously approved protocol. The amendment form and a copy of the supplement are to be submitted for review and approval.

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14.2 IRB Review of Just-in-Time (JIT) Protocols

What is a “Just-in-Time” (JIT) Request

The NIH just-in-time policy defers the submission of several proposal elements for grant submissions until after completion of Scientific Review and prior to Council Review and a decision of award. This policy is an effort to focus the NIH review on the science and to save the applicant time and effort submitting materials for a grant that might not be funded. One of the elements that can be withheld are protocol approvals.

A JIT notice is activated via an automated email from NIH to researchers with submissions that receive an impact score of 40 or less from the Scientific Review, regardless of the assigned Institute’s pay line. JIT requests are not a Notice of Award or even an indicator of possible funding. JIT requests are another step in the process of obtaining NIH funding.

Process for Obtaining Committee Approvals in the event of JIT Request

As soon as the researcher receives the automated notice from the NIH, he/she must evaluate whether or not the application has an impact score that merits committing time to the JIT process. NOTE: It is not necessary for the researcher to submit a protocol if the priority ranking is unfavorable.

If there is merit, the PI should contact their RPO analyst as soon as possible to discuss the recommended level of Committee review for the project. Full meetings are scheduled monthly. If the agenda allows, JIT protocols will be added to the next available convened meeting. The Committee does not have a mechanism to convene a separate meeting specifically for JIT. NIH, however, allows you to submit approvals at the earliest date they become available. You should be in communication with your program officer regarding timing of Committee approvals. While obtaining Committee approvals may delay an award it should not affect receipt of an award.

If the JIT request is a new or competing renewal and is identical or substantially similar to a previously approved protocol, see New Competing or Competing Renewal Grant Applications for further guidance.

If the JIT request is for a resubmission, see section New Competing or Competing Renewal Grant Applications for additional guidance.

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14.3 Grant Proposals Lacking Definite Plans for Involvement of Human Subjects

Certain types of applications may involve human subjects (within the funding period) but definite plans are not included in the application or protocol. This type of application would include such activities as institutional grants, training grants, and projects in which human subjects' involvement will depend upon completion of instruments, prior animal studies, or purification of compounds. Regulations give federal agencies and their grantee institutions the discretion to allow a limited release of federal research funding to investigators without approval or exempt status. Conditions include:

  • Human subjects involvement will depend upon completion of significant pre-human subjects development activities, or
  • The award is for a clinical research network or consortium that plans to add new protocols over the course of the award, or
  • The award is for funds that will be awarded to specific projects that will be selected and funded by the awardee (e.g., a pilot project program; some training grants).

The IRB must certify that all human subjects research contained within a grant application has been reviewed and approved prior to release of funds, even if the plans for human subject involvement is unknown. The NIH refers to these as “delayed onset awards”. Therefore, investigators should submit the “Initial Review of a Delayed Onset of Human Subjects Research or Projects to be Developed” form. “Delayed Onset of Research” review is recognized by the IRB only as a compilation of research being conducted under a specific grant. It does not constitute a review of the risk/benefit ratio of protocols to be conducted under it. 

NIH guidance states that PIs are required to obtain prior approval from the sponsor for the addition of human subject research activity prior to implementation. See notice below for additional information. Those protocols (including informed consent documents) must be submitted for IRB review and approval separate from this request.  The grant will also be reviewed and approved with the separate protocol submissions.

  • Prior NIH Approval of Human Subjects Research in Active Awards Initially Submitted without Definitive Plans for Human Subjects Involvement (Delayed Onset Awards)
    (NOT-OD-12-130) National Institutes of Health

No human subjects may be involved until the project has been reviewed and approved by the IRB and certification of approval submitted to the funding agency.

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14.4 Contracts/Agreements

Protocols which are supported by an industry sponsor where money, materials (test articles, equipment, or other supplies), or intellectual property are exchanged require a contract or agreement be in place between the sponsor and either UVM or UVM Medical Center. Most industry-sponsored research contract review is done through the Office of Clinical Trial Research (OCTR) however a select few are handled through SPA.

The IRB requires a copy of the final contract prior to release of a protocol approval. OCTR/SPA will forward a copy of the final contract to the IRB who will review for potential conflicts of interest and appropriate subject payments. Many times this contract review is the final step to protocol approval and release, so researchers should plan accordingly and submit their contracts to the appropriate individuals early in the review process.

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14.5 Changes to the Scope of a NIH Awarded Project

While most of the University’s NIH grants are under Expanded Authorities, eliminating the need for prior approval for most budget changes, NIH still requires prior approval before making changes that NIH considers changes in project scope.

The NIH Grant Policy Statement provides examples of actions requiring approval before they are made. Investigators should consult the complete NIH Grants policy statement for changes that may involve a change in scope.

In 2012 the NIH issued additional guidance for changes that involve human subjects in active awards and that will require prior NIH approval. (NOT-OD-12-129).

Some actions that may require prior approval as they represent a change in scope include:

  • Change in the specific aims approved at the time of award
  • Substitution of one animal model for another
  • Any change from the approved use of animals or human subjects
  • Shift of the research emphasis from one disease area to another
  • Application of a new technology
  • Transfer of the performance of substantive programmatic work to a third party if the third party is a foreign component
  • Change in key personnel including withdraw from the project, absence during any continuous period of three-months or more, reduction in time devoted to the project by twenty-five percent or more.

Prior approvals may be requested by an email from a University Authorized Official to the project’s Grants Management Officer. If you would like to request prior approval for any of the changes mentioned above, please be in touch with your SPA administrator. Your administrator will advise you on the content of the email request, review it, and forward it to the University’s Authorized Official who will send it on to NIH.

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14.6 Fees for Committee on Human Research Review of Sponsored Trials

Policy

The University’s Institutional Review Boards (IRBs) charge fees for initial review and annually for the life of the protocol for University of Vermont (UVM) and University of Vermont Medical Center (UVMMC) studies.

Fees will be applied to these types of protocols:

  • Industry
  • Pharmaceutical companies
  • Other for profit entities
  • Non-profit entities where such fees are not prohibited
  • Investigator-initiated protocols with for profit sponsors
  • Protocols initiated by affiliated Health Network sites

Fees will not be applied to these types of protocols:

  • Federal or federal flow through
  • State of Vermont
  • Non-profit where fees are prohibited
  • Investigator-initiated internally -funded studies.

IRB Fee Schedule

The fee schedule is reviewed each year by the IRB and is subject to change.

Initial Fee: $2,500.00

Annual Fee: $1,500.00

Network Affiliate Reliance Fee: TBD

The annual fee covers expenses of ongoing IRB review activities such as amendments, consent revisions, unanticipated events and compliance issues. It is not strictly tied to whether there is a continuing review.

Budgeting though the Office for Clinical Trials Research (OCTR) for IRB Fees

Contracts and budgets for industry or pharmaceutical-initiated projects are typically supported through OCTR. OCTR negotiates with sponsors to include the IRB fees in project budgets during the proposal negotiation processes. Many investigators like to include a “regulatory” fee as part of their budget. The regulatory fee covers the research coordinator cost of preparing materials for IRB review. This is a separate fee from the IRB fee and OCTR identifies these as separate line items in the budget.

Budgeting though Sponsored Projects Administration (SPA) for IRB Fees

Contracts and budgets for investigator-initiated with for profit sponsors and not for profit entities that do not prohibit IRB fees, are typically supported by SPA. There is a line item in the budget worksheet that addresses the required IRB fees. If the sponsor does not wish to provide fees, written justification must be provided. SPA will assist with negotiation of these fees. Many investigators like to include a “regulatory” fee as part of their budget. The regulatory fee covers the research coordinator cost of preparing materials for IRB review. This is a separate fee from the IRB fee and should be identified as a separate line item in the budget.

Frequently Asked Questions

When will the initial fee be charged?

  • The initial IRB fee for both full and expedited review studies, negotiated through OCTR, are invoiced monthly after the full Committee meeting.
  • The initial IRB fee for both full and expedited review studies, negotiated through SPA, are invoiced once the initial protocol review is complete.

How are IRB fees paid?

  • For studies negotiated through OCTR, the researcher or their research staff indicate that IRB fees apply. IRB provides an excel spreadsheet of applicable studies and once verified, OCTR staff initiates payment through University of Vermont Accounting services.
  • For studies negotiated through SPA, IRB staff will charge the study account by electronic journal.

What happens if the contract or study is not approved?

The IRB fees are assessments of real cost associated with protocol review by the IRB.  If subjects are never enrolled, the study terminates before milestones are met, expenditures exceed revenue, or a contract is never finalized, the investigator and department are responsible for all expenditures not covered by the sponsor, including the initial and any annual IRB fees.

When will the annual fee be charged?

The annual fees will be invoiced once per year after initial approval.

What if I wish to re-open a protocol after I closed it?

If you have requested that a protocol be re-opened after it has been closed, an annual fee will be applied regardless of when the prior review was conducted.

Will there be exceptions made to this policy?

Exceptions to this policy will be considered on a case-by-case basis by appropriate institutional officials. Requests for consideration must be submitted by the Principal Investigator or Sponsor in writing to the IRB. Requests for outright waiver of the fee must be received prior to protocol submission to the IRB.

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15. Amendment to Previously Approved Protocol

Requirement

Review of any changes to previously approved research is required by federal regulation [45 CFR 46.103(b)(4)] and is an essential element of the continuing review of research involving human subjects.

The IRB recognizes that research is a continuous process and that changes in the conduct of a study and/or changes to the consent document are necessary. However, no changes to an approved protocol should be implemented until the Committee has reviewed and approved the changes. This includes, but is not limited to, subject recruitment methods, consent form changes, treatment changes, amendments to the sponsor’s master protocol as well as changes or additions in study sites, investigators, or key personnel.

The CRC and UVMCC also require review of changes to protocols under their purview. Check their respective websites for further guidance.

Major Amendments

Major modifications/amendments potentially affecting the risk/benefit ratio are reviewed through the full committee review process.

When amendments impact the safety of subjects previously enrolled who continue to receive study interventions, it may be necessary to convey this information (e.g., to obtain the consent of the subjects) by means of an addendum to the existing consent form or providing the subjects with an informational sheet regarding the update (Consent). The IRB may determine, for example, that such subjects must be notified of new findings or toxicities not noted at the time they were originally consented. Such notification is consistent with the view of informed consent as a continuous process, and affords subjects the opportunity to determine whether or not they wish to continue their participation in the research. IRB policy is that a consent addendum be used instead of requesting the subject sign a full copy of the newly revised consent. Requesting subjects sign a full consent each time there is a revision is a practice that can confuse subjects unnecessarily. The IRB shall determine on a case-by-case basis when such notification, and its documentation, is required.

Minor/Administrative Amendments

Minor modifications not affecting the risk to subjects may be reviewed through the expedited review process.

Immediate Hazard

Federal regulations mandate that changes cannot occur until after IRB review and approval “except when necessary to eliminate apparent immediate hazards to the subject." The FDA has comparable criteria for implementing changes [21 CFR 56.108(a)(4)].

The definition of immediate hazard, as stated in the federal regulations for amendments, encompasses only those few instances where the immediate well-being of the subject is at risk. To that end, the subject’s well-being must benefit from

(1) continuing the research itself (rather than just discontinuing the research intervention and treating with standard of care) and

(2) the research must be changed immediately for the well-being of the subject.

Subjects may always be treated based on a physician’s determination of their needs, but might not be eligible to continue in the research protocol. If a protocol is clinically faulted it should be corrected (through the amendment process) and the patient should normally be removed from the protocol and treated with the standard of care.

Example of “Immediate Hazard”: A subject has been enrolled on a local surgical protocol. The protocol requires that a certain immune-suppressing medication be administered to the subject during surgery, but the subject has an allergic reaction to that medication once surgery commences. The physician would determine the appropriate medical course of action and, if appropriate, the procedure would proceed.

Immediately following the procedure the PI must:

- notify the IRB; then

- the PI must submit a “Unanticipated Problem Potentially Involving Risk…” form documenting the event;

- the PI should submit a “Request for Modification / Amendment to Approved Protocol” form altering the protocol to allow for treatment or optional medications in case of allergic reactions (if appropriate); and

- the PI must ask the Committee to determine if the subject can be included in the study population as the protocol, as approved by the Committee, was not followed for this subject.

Requesting an Amendment

Amendment requests may be submitted at any time but must be approved before any changes can be implemented in the conduct of the protocol.

Submit a completed “Request for Modification / Amendment to Approved Protocol" form to the Committee with all revised documents (i.e., protocol, questionnaires, recruitment flyers, consents, etc.) Please ensure that you have included a revised date to your materials.

If the amendment resulted in a revision to the consent form, the revised consent will be stamped with a new IRB approval date. This helps to track which consents apply to which version of the approved protocol.

Documentation

Once approved, the Committee will forward approval and a stamped consent form (if applicable) to the PI via email. Proof of the amendment approval as well as the stamped consent form must be kept by the PI (perhaps in a Research Regulatory Binder) as evidence that the Committee has approved the change.

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16. Continuing Review

Requirements

Federal Policy: Continuing review of research activity is required by federal regulations [(45 CFR 46.109 subpart (e)].

It is the policy of the IRB to review human research appropriate to the degree of risk involved, but not less than once per year. “Higher risk” research (as determined by the Committees on Human Research – hereafter “Committee”) may require more frequent reviews.

The purpose of continuing review is to determine:

1) whether the risks to subjects continue to be minimized and reasonable in relation to the anticipated benefits;

2) whether the selection of subjects continues to be equitable;

3) whether the informed consent continues to be appropriate;

4) changes in key personnel and whether mandatory training is complete;

5) whether there continue to be:

a. adequate provisions for monitoring the data collected to ensure the safety of the subjects, when appropriate;

b. adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data, when appropriate; and

c. appropriate safeguards for vulnerable populations.

All research protocols (except protocols determined by the Committee to qualify for exempt status) must undergo continuing review at least once a year, unless all research activity, including data analysis, has been completed.

Continued Approval Policy

In order to resolve the issue of indefinitely reviewing and reapproving protocols annually for which work has not ever been started, the IRB approved the following policy:

If the work on a research protocol has not yet begun after a three-year period, the protocol will be administratively closed by the IRB. A new protocol must be submitted for review at the point in time when activity is anticipated to begin. Exceptions may be made if the funding period exceeds three years and the human subjects’ protocol is not scheduled to begin until after that time period. You must indicate that is the case on your continuing review form.

In addition, the committee will be closing at time of continuing review any non-treatment protocols in which there has been no activity within the last 5 years.

This policy does not apply to protocols that have been and plan to remain open to accrual but have just not had any enrollment to date, such as many of the oncology group protocols that are approved for rare tumors. For that situation, the category “active - work in progress” should be checked on the continuing review form.

When to Report

The Committee will send a “Request for Continuing Review” form to the PI approximately three months before the approval is due to expire. Reminders will be sent at two months and one month prior to expiration.

Identifying the Point When Continuing Review is no Longer Necessary

Continuing review and re-approval of a research project at least annually is required so long as the project continues to involve human subjects.  OHRP considers a research project to continue to involve human subjects as long as the investigators conducting the research continue to obtain:

  • Data about the subjects of the research through intervention or interaction with them; or
  • Identifiable private information about the subjects of the research.

With respect to obtaining identifiable private information, OHRP considers this to include obtaining identifiable biological specimens originating from living individuals.  Furthermore, OHRP considers obtaining identifiable private information to include

  • Collecting or receiving identifiable private information (including identifiable biological specimens) from any source (i.e., not already in the possession of the investigator);
  • Collecting identifiable private information by observing or recording private behavior without interacting or intervening with the human subjects; and
  • Using, studying, or analyzing identifiable private information (including identifiable biological specimens), even if the information was already in the possession of the investigator before the research begins.  This includes using, studying, or analyzing any of the following:
    • Identifiable private information obtained by interacting or intervening with the human subjects;
    • Identifiable private information stored in documents, records, photographs, images, video recordings, or audio recordings provided to the investigators from any source;
    • Identifiable private information stored in documents, records, photographs, images, video recordings, or audio recordings already in the possession of the investigator before the research begins;
    • Identifiable private information obtained about an individual by interviewing other people (e.g., an individual’s healthcare provider or teacher);
    • Identifiable biological specimens provided to the investigators from any source; or
    • Identifiable biological specimens already in the possession of the investigator before the research begins.

A research project no longer involves human subjects once the investigators have finished obtaining data through interaction or intervention with subjects or obtaining identifiable private information about the subjects, which includes the using, studying, or analyzing identifiable private information.  Once all such activities described in the IRB-approved protocol are finished, the research project no longer needs to undergo continuing review.  For example, when the only remaining activity of a research project involves the analysis of aggregate data sets without individual subject identifiers, no further continuing review is necessary.  At that point the IRB can formally close the IRB file for that project and advise the investigator of that action. 

The Committee requires the PI to submit final closeout report for all protocols when a research study no longer involves human subjects. The PI must submit a continuing review form to officially change the designation to “Not Human Subjects”. A “Not Humans Subjects” certification will be forwarded to the PI for their records. Once the protocol has been certified with this designation, continuing reviews are no longer required.

Expired Approvals

Extensions beyond the expiration date cannot be granted. If the expiration date has passed, or is in jeopardy of passing, the Committee must be notified as soon as possible.

a) If the Committee does not provide continued approval of the research by the specified expiration date, subject accrual is suspended pending continued approval of the research by the Committee. Note: A valid consent form will not be available until after the Committee reviews and approves a continuation of the research.

b) Where subjects are patients in treatment studies, continuation of research interventions or interactions is allowable for the safety and well-being of the individual and is reportable to the IRB.

c) Department chairs and Faculty Sponors (if applicable) will be notified of a lapse in a researcher’s IRB approval.

d) Researchers found to be collecting data without a current IRB approval may not be allowed use the data.

As part of the continuing review process, the Committee may require that the research be restricted, modified, reviewed more frequently or terminated/suspended if risks have changed during the review period. Alternatively, special precautions or Committee-imposed restrictions, or shortened review periods, may be modified if current data support such actions. Ongoing approval will not be released until requested clarifications or changes have been received.

The most visible element of the continuing review process is the stamped IRB approval date on the signature page of the consent form.

Request for Continuing Review Form

The “Request for Continuing Review (DOCX)” form is intended to capture all of the required elements for a significant review of the research. This is located in the continuing review of our IRB forms page and should be downloaded each time you need one. Incomplete forms will be sent back to the investigator.

Documentation

a. Once approved, the Committee will return a signed Protection of Human Subjects Assurance and a stamped consent form (if applicable) to the PI via email.

b. Proof of continuing review must be kept by the PI (perhaps in a Research Regulatory Binder) as evidence that Continuing Review has occurred. The documentation should include:

i. An IRB Approval Memo;

ii. A signed Protection of Human Subjects Assurance;

iii. A stamped and dated consent form (if applicable);

iv. Copies of all additional documentation (e.g. amendments) submitted to the Committee at the time of Continuing Review.

**** The single most important practice to ensure compliance with the continuing review process is to make certain that the consent form given to the subjects is current (i.e., with a Committee approval stamp) ****

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16.1 Continuing Review (New section! Do not reference until the 2018 revised Common Rule takes effect)

Requirements

Federal Policy: Continuing review of research activity is required by federal regulations [(45 CFR 46.109 subpart (e)].

It is the policy of the IRB to review human research appropriate to the degree of risk involved, but not less than once per year. “Higher risk” research (as determined by the Committees on Human Research – hereafter “Committee”) may require more frequent reviews.

The purpose of continuing review is to determine:

1) whether the risks to subjects continue to be minimized and reasonable in relation to the anticipated benefits;

2) whether the selection of subjects continues to be equitable;

3) whether the informed consent continues to be appropriate;

4) changes in key personnel and whether mandatory training is complete;

5) whether there continue to be:

a. adequate provisions for monitoring the data collected to ensure the safety of the subjects, when appropriate;

b. adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data, when appropriate; and

c. appropriate safeguards for vulnerable populations.

Research protocols having a more than minimal risk determination (full committee review) are required to undergo a continuing review at least once a year. Continuing review is not required for some minimal risk research, including studies where the only remaining activity is the analysis of identifiable data/biospecimens or activity to obtain follow-up clinical data.

While the majority of expedited studies will not require continuing review, there may be reasons for maintaining the continuing review requirement such as:

  • The project is regulated by the Food & Drug Administration (FDA) or by another sponsor that requires continuing review
  • An amendment or incident report reveals new findings that require additional oversight
  • A Delayed Onset protocol has been received and the PI needs to develop and submit the human subjects protocol described in the grant application
  • The investigator has had previous serious non-compliance or a pattern of non-serious non-compliance. In these instances the investigator will be notified along with justification for the continuing review requirement.

Continued Approval Policy

In order to resolve the issue of indefinitely reviewing and reapproving protocols annually for which work has not ever been started, the IRB approved the following policy:

If the work on a research protocol has not yet begun after a three-year period, the protocol will be administratively closed by the IRB. A new protocol must be submitted for review at the point in time when activity is anticipated to begin. Exceptions may be made if the funding period exceeds three years and the human subjects’ protocol is not scheduled to begin until after that time period. You must indicate that is the case on your continuing review form.

In addition, the committee will be closing at time of continuing review any non-treatment protocols in which there has been no activity within the last 5 years.

This policy does not apply to protocols that have been and plan to remain open to accrual but have just not had any enrollment to date, such as many of the oncology group protocols that are approved for rare tumors. For that situation, the category “active - work in progress” should be checked on the continuing review form.

When to Report

The RPO office will send a “Request for Continuing Review” email to the PI and any study contacts approximately three months before the approval is due to expire. Reminders will be sent at two months and one month prior to expiration.

Expedited non-FDA regulated research that fits the criteria for no longer having to submit yearly continuing review reports still have ongoing responsibilities. Investigators are required to notify the IRB when the protocol is closed. The IRB has developed an annual update inquiry that will be sent to investigators to obtain that information. The system reminder will be sent prior to the last anniversary approval date for the study. The IRB must receive confirmation on an annual basis that the research is still ongoing and that no changes have been made to the research that would require the IRB to conduct continuing review of the research. PI’s are required to log into the InfoEd system and add an "Annual Update" submission to the protocol. An electronic-form will ask the PI if the protocol is to remain open or closed, have the PI review and update the key personnel roster and remind the PI to submit any protocol changes at this time.

Even when continuing review is not required for a project, the PI and study team must continue to submit the following items in real-time:

  • amendments for protocol changes
  • adverse events, noncompliance and unanticipated problems
  • DSMB and IDB reports
  • key personnel roster updates
  • protocol closure
  • notice when personal identifiers are removed from the data/biospecimens and all codes and keys are destroyed

Expired Approvals

Extensions beyond the expiration date cannot be granted. If the expiration date has passed, or is in jeopardy of passing, the Committee must be notified as soon as possible.

a) If the Committee does not provide continued approval of the research by the specified expiration date, subject accrual is suspended pending continued approval of the research by the Committee. Note: A consent form should not be used to enroll new subjects until after the Committee reviews and approves a continuation of the research.

b) Where subjects are patients in treatment studies, continuation of research interventions or interactions is allowable for the safety and well-being of the individual and is reportable to the IRB.

c) Department chairs and Faculty Sponsors (if applicable) will be notified of a lapse in a researcher’s IRB approval. The Committee views the lapse of protocol approval as noncompliance.

d) Researchers found to be collecting data without a current IRB approval may not be allowed use the data.

As part of the continuing review process, the Committee may require that the research be restricted, modified, reviewed more frequently or terminated/suspended if risks have changed during the review period. Alternatively, special precautions or Committee-imposed restrictions, or shortened review periods, may be modified if current data support such actions. Ongoing approval will not be released until requested clarifications or changes have been received.

Request for Continuing Review Form

The “Request for Continuing Review” form is intended to capture all of the required elements for a significant review of the research. This is located in the continuing review of our IRB forms page and should be downloaded each time you need one. Incomplete forms will be sent back to the investigator.

Documentation

a. Once approved, the Committee will return a signed Protection of Human Subjects Assurance to the PI via email.

b. Proof of continuing review must be kept by the PI (perhaps in a Research Regulatory Binder) as evidence that Continuing Review has occurred. The documentation should include:

i. An IRB Approval Memo;

ii. A signed Protection of Human Subjects Assurance;

iv. Copies of all additional documentation (e.g. amendments) submitted to the Committee at the time of Continuing Review.

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17. Closing or Reopening a Protocol

Investigators have the responsibility to formally close a study with current IRB approval once it is completed or discontinued. Among other reasons for closing out a study, this informs the IRB on the conduct and outcomes of the study, including any risks or problems that may have arisen since the last study renewal and which may need to be disclosed to the study participants or others.

Criteria for Closing a Protocol

Do not close-out a study if any of the following conditions apply as human subject protections are still required.

  • Enrollment ongoing.
  • Research-related interventions and/or follow-up ongoing.
  • Subject follow-up ongoing.
  • Biological specimens containing personally identifiable information are being maintained in a repository that has been approved as part of this study or upon which analysis or research is ongoing. If, however, specimens have been transferred to a separate repository that has ongoing IRB approval, the study may be closed.
  • Primary data analysis or manuscript preparation that involves the use or access to personally identifiable information ongoing.
  • If there is an external study sponsor and the sponsor has not provided permission to close the study with the IRB.

Notification of Closure to the IRB

Notification must be done by completing a Request for Continuing Review form. This provides the opportunity for the researcher to summarize all the activities into a final report. Researchers can not use an amendment form to close a protocol as a final report is required.

Storing Data

In addition to informing the IRB of the closure, the PI must store the research records for the required length of time in accordance with the federal regulations, UVM policy, and any additional requirements stipulated by research sponsors and/or investigators’ professional associations. See Records Retention section.

The PI must continue to follow appropriate data security procedures.

Subsequent Use of Data

Subsequent use of data collected under a closed protocol, whether by the original investigator or other investigators, may constitute human subjects research requiring IRB approval or a determination of Exemption from IRB review. For further information about storage of data, determinations of not human subjects, or future use and secondary uses of data, please see the Guidance on Data Management section.

If the principal investigator is leaving the institution, it is the principal investigator’s responsibility to either close the study or transfer the protocol to another UVM/UVM Medical Center principal investigator. See Managing Research Prior to Departure information.

Closure by Committee

The IRB may close projects without UVM/UVM Medical Center investigator notification in the following circumstances:

  • If the work on a research protocol has not yet begun after a three-year period.
  • Non-treatment protocols in which there has been no activity within the last 5 years.
  • If it is determined that the investigator is no longer affiliated with UVM/UVM Medical Center.
  • If the approval period for the research has expired, the study is closed to subject accrual and the IRB has not permitted ongoing research procedures for the safety of continuing subjects.
  • If the investigator has not responded to the IRB’s requests for revisions and/or clarifications within a reasonable timeframe, 120 days, and an extension has not been requested.
  • If the IRB approval has been terminated for compliance issues. This would only occur after IRB review and communication with the investigator. Termination of IRB approval is reportable to the appropriate federal department or agency head and institutional officials.

In any of the situations described above, the IRB office will notify the PI, as well as his/her department chair, of the study closure.

Reopening a Protocol

If the investigator needs to reopen a protocol and less than one year has passed since closure, a completed continuing review form must be submitted for review and approval. If the study is billable, it will be invoiced for this review regardless of the amount of time that has passed. If the study has been closed for greater than one year, a new protocol submission is required. If the study is billable, the review will be invoiced.

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18. Unanticipated Problems Reporting (includes adverse events)

Requirement

Review of unanticipated problems involving risk to subjects or others (hereinafter referred to as unanticipated problems) is required by federal regulations (45 CFR 46.103(b)(5) and for FDA regulated articles 21 CFR 312 and 21 CFR 812), and is an essential element of the continuing review of research involving human subjects.

The IRB is required under 45 CFR part 46 to submit to the Office for Human Research Protections (OHRP) any unanticipated problems involving risk to subjects or others (UAPs). [21 CFR 56.108 (b)(1) & 45 CFR 46.103(b)(5)(i)]. OHRP considers UAPs, in general, to include any incident, experience, or outcome that meets all the following criteria:

  1. unexpected (in terms of nature (type of event), severity (extent of harmfulness), or frequency (number of like events higher than anticipated) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
  2. related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

All UAPs must be promptly reported to the IRB. Investigators are encouraged to contact the Committee office for clarification in ambiguous circumstances. UAPs are to be submitted using the "Unanticipated Problem Potentially Involving Risk ….(DOC)" Form.

To assist investigators in identifying a UAP we have listed below four general categories of unanticipated problems that may require local reporting to the Committee.

Local Adverse Event

A local adverse event (includes death) is a negative side effect resulting from the study intervention that occurred to a subject enrolled at UVM, UVM Medical Center, or other research site under the jurisdiction of the UVM IRB.

  • UNEXPECTED: Any adverse event occurring in one or more subjects participating in a research protocol, the nature, severity, or frequency of which is not consistent with either: the known foreseeable risk of adverse events associated with the protocol procedures described in the (a) IRB-approved protocol, any drug or device brochure, and the IRB-approved informed consent, and (b) other relevant sources of information, such as product labeling and packing inserts; or
  • the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.

The vast majority of adverse events occurring in the context of research are expected in light of (1) the known toxicities and side effects of the research procedures; (2) the expected natural progression of subjects’ underlying diseases; and (3) subjects’ predisposing risk factors. Thus, most individual adverse events do not meet this criterion for an unanticipated problem and do not need to be reported.

  • RELATED: An adverse event is considered to be related if there is a reasonable possibility that the event may have been caused by the protocol or study interventions. A related event has a strong temporal relationship to the drug, device or intervention, and an alternative etiology is unlikely. Adverse events that are determined to be solely caused by (2) or (3) above would be considered unrelated to participation. If it cannot be determined whether an event is related, it should be reported as “possibly related.”

NOTE: The IRB may, in coordination with other institutional oversight committees, categorize a protocol as “higher risk” and require the Investigator to follow a specific “high risk” reporting procedure. This high risk determination will be made at time of initial review or any time after initial review if the IRB feels it is warranted. This determination and the requirements will be clearly communicated back to the Investigator. Examples of higher risk protocols of clinical trials for which the IRB may institute more stringent reporting are: local, investigator-initiated early phase (Phase I, Phase I/II) study without a DSMB; local, investigator-initiated trial in extremely vulnerable populations, e.g., very sick patients, subjects unable to consent for themselves, prisoners.

Adverse events that are not reportable to the Committee may also require reporting to UVM Medical Center SAFE, UVM Medical Center or UVM Risk Management, the sponsor and/or the FDA. Do not forward copies of reports that do not meet local reporting criteria to the Committee.

Interim Study Findings/New Safety Information

New Safety Information that requires a change to the protocol or consent form must be reported to the IRB utilizing the “Unanticipated Problem Potentially Involving Risk…(DOC)” form. A “Request for Amendment (DOCX)” form and applicable materials must accompany the report. Examples of new safety information are below:

Revised Investigator Drug/Device Brochures (IDB);

Toxicity Reports/NCI Action Letters;

Data and Safety Monitoring Reports/Progress Reports;

Literature Reviews; or

other safety information that may impact human subject welfare.

New Safety Information that does not require a change to the protocol or consent form must be reported to the IRB utilizing the “New Safety Information Not Affecting Risk to Subjects” form. Receipt of these submissions will be acknowledged.

Protocol Deviations

A protocol deviation is a divergence or departure from the expected conduct of an IRB-approved study that is not consistent with the current, approved research protocol, consent process or document or study addenda. The significance of a protocol deviation, in terms of subject safety, depends on the nature of the deviation and the study.

Protocol Deviations Involving Harm or Potential for Harm

Those protocol deviations that involve harm or have the potential to impact the health or welfare of the subject(s) or others must be reported in writing to the IRB by utilizing the “Unanticipated Problem Potentially Involving Risk…(DOC)” form. Examples of reportable deviations are below:

  • Medication or Laboratory Errors - administered as part of the research that involved increased risk to subjects;
  • Improper or Unapproved Consent Process or Consent Form;
  • Unintentional change to the protocol without prior IRB approval;
  • Intentional change to the protocol without prior IRB approval to eliminate immediate hazard to research subject.

Protocol Deviations that do not Involve Harm or Have Potential for Harm

Those protocol deviations (e.g., missed appointment, labs one day late) that do not involve harm or have the potential to impact the health or welfare of the subject(s) or others do not need to be individually reported. The PI needs to make this determination for each deviation. Deviations not affecting risk to subjects or others should be summarized and reported at time of continuing review for any FDA regulated protocols.

Other Unanticipated Problems

Other unanticipated problems are those which are 1) unexpected, 2) related, AND 3) involve harm or have the potential for harm to subjects or others. Below are examples of other types of protocol-related problems that must be reported to the IRB:

  • Complaint by a subject;
  • Breach of confidentiality/HIPAA violation;
  • Enforcement action e.g., unfavorable audit report, suspension or disqualification of investigator, FDA Form 483 or Warning Letter;
  • Study personnel misconduct;
  • Study personnel not on protocol;
  • Incarceration of a research subject during participation;
  • Other untoward events that present risk to the subject, investigator, research staff or others.

These unanticipated problems are to be reported to the IRB utilizing the “Unanticipated Problem Potentially Involving Risk…(DOC)” form.

IND Safety Reports and Study Progress Reports

Individual IND Safety Reports do not necessarily meet the reportable criteria and are recognized by OHRP and the FDA to not yield information that is useful to IRBs. The reports often lack context and detail, are often incomplete and unanalyzed, and as such, inhibit an IRB’s ability to assure the protection of human subjects. Therefore, IND safety reports do not require submission to the IRB. Similarly, study progress reports do not provide any additional safety information and are not reportable to the IRB.

However, if an individual IND report results in a revision to the protocol or consent, an a copy of the specific IND safety report, an Amendment Request form along with applicable materials, as well as an “Unanticipated Problem Potentially Involving Risk…(DOC)”must be submitted..

Notification Timelines for Reporting Unanticipated Problems

All unanticipated problems are to be reported as soon as possible. If all information is not available within 7 days, submit an initial report at 7 days and then follow-up with the IRB as information becomes available.

Disposition of Submissions and Communications Regarding Submissions

Unanticipated problems, as defined above, will be reviewed by the Safety Subcommittee.

If it is determined that the protocol or consent require revision or there are other corrective actions that are necessary, a request will be sent to the PI and/or study contact.

If the protocol and or consent do not require revision and there are no other corrective measures that are necessary, a memo stating that no further action is required will be sent to the study contact.

Only the full Committee will make determinations regarding additional reporting to the Office for Human Subject Protections (OHRP).

For new safety information that is not considered a UAP (e.g. does not require protocol or consent revisions), the IRB will acknowledge receipt.

Documentation

The PI must keep a copy of the “Unanticipated Problem Potentially Involving Risk…(DOC)” form (perhaps in a subject’s Research Binder) as evidence of IRB submission.

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19. Incidental Findings in Neuroimaging Protocols – Detection and Management

University and UVM Medical Center researchers must make adequate provisions for monitoring the data collected to ensure the safety of subjects. In the course of study monitoring, information incidental to the research goals may be identified which may impact the safety and/or wellbeing of the subjects. Scientists and clinicians should anticipate the potential for incidental findings in experimental design and establish a process to handle the discovery of an incidental finding.

Incidental Finding – Definition

A finding discovered in the course of research participation for which there is potential health importance. An incidental finding is beyond the specific aims of the protocol.

Note: The UVM MRI Research Center 3T magnet is not considered a clinical magnet and therefore neither the images nor reports can be incorporated into the subjects’ clinical medical record and should not be used for diagnosing or treating medical conditions. Any abnormality found utilizing this magnet would be considered an incidental finding.

IRB Requirements Regarding Protocols Which May Have Incidental Findings

The IRB requires that the way in which incidental findings will be handled is made explicit in the study design. The IRB also requires that the way in which incidental findings will be handled is made explicit to any potential research subject through the informed consent process.

Research x-rays that are included in a protocol should not be designed nor intended to detect health problems in subjects. The x-rays required as part of a research study do not substitute for an appropriate medical examination by a qualified health care provider. The information from these x-rays should not be shared with the subject or their personal physician, unless there is an incidental finding.

Disclosure of clinically meaningful findings should be conducted by a licensed physician (or psychologist, genetic counselor, or other professional as appropriate) whenever possible. The person responsible for communicating an incidental finding must be referenced in the plan for disclosure submitted to the IRB.

Consent Template Section

Incidental Findings

There is a possibility that while reviewing your (insert test) we may see an abnormality that may have health implications that we did not expect to see. This is what is called an “incidental finding.”

If we see an incidental finding, a qualified person (usually a member of the research team) will communicate the information to you. If you wish, we will provide information about this incidental finding to your primary doctor or we will refer you to an appropriate doctor for further evaluation.

This study is neither designed nor intended to detect health problems. The imaging that you will have as part of this research study does not substitute for an appropriate medical examination by a qualified health care provider. If you suspect that you might be suffering from injury or illness, you should not rely on this study as a way to determine your health status. The information from this image will not be shared with you or your personal physician, unless (as mentioned above) there is an incidental finding.

An incidental finding may cause you to feel anxious. If you have further tests done, those results will then become part of your medical record, which may affect current and future health or life insurance. The costs for any care that will be needed to diagnose or treat an incidental finding would not be paid for by this research study. These costs would be your responsibility.

 

19.1 Standards and Language for Studies Involving MRI

UVM has determined MRI procedures to be greater than minimal risk whenever the device is employed for research purposes if intravenous contrast, sedation, or drugs are also being used, since the probability and magnitude of harm or discomfort anticipated in the research are greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests [45 CFR 46.102(i)]. These protocols require full review.

For studies involving normal, healthy subjects in which sedation, drugs, or contrast are not used, or studies involving subjects with a disease/condition when the MRI/fMRI does not pose any additional risk, the study may be deemed to present no greater than minimal risk, as the probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. These protocols can undergo an expedited review.

This document reflects standard procedures accepted by the IRB for research protocols involving magnetic resonance imaging (MRI) and functional MRI (fMRI). It provides guidelines for how to describe the procedures in the protocol and consent form. These standards do not apply to therapeutic imaging.

MRI Risk Information for Researchers

1. Risks due to the static magnetic field of the scanner

The powerful magnetic field of the scanner can attract certain metallic objects known as “ferromagnetic” objects, causing them to move suddenly and with great force towards the center of the MR system (projectiles). This may pose a risk to the patient or anyone in the way of the object, and has resulted in several deaths worldwide.

  • Great care must be taken to prevent ferromagnetic objects from entering the MR scan room. It is vital that anyone entering the scan room removes metallic objects, including watches, jewelry, and items of clothing that have metallic threads or fasteners.

The powerful magnetic field of the scanner can also exert a force on metallic implants and other materials inside the subject’s body, including (but not limited to) aneurysm clips, metallic fragments in the eye, and bullets. Movement of such objects can cause serious injury or death.

  • Researchers must screen potential subjects for possible metal in their body and assume that such metal is unsafe, unless it has been approved by qualified personnel.

2. Risks due to time-varying magnetic field gradients

MRI uses spatial and time-varying magnetic field gradients to form images. Switching the electrical current used to generate these gradients results in the loud sounds associated with MRI. These rapidly varying magnetic fields can also induce electrical currents into conducting wires, such as cardiac monitoring leads and implanted electrical devices (which might cause the device to fail). It is also possible to stimulate nerves (peripheral nerve stimulation), although the scanner is designed to operate at FDA-approved limits below this level.

  • Subjects are required to wear earplugs or headphones to protect their hearing.
  • Care must be taken to use only MRI-compatible electrical devices. Correct placement of leads and devices is essential to their safe operation.
  • Patients with implantable electrical devices are not to be scanned
  • Subjects to be instructed not to cross their hands or feet to minimize the chance of peripheral nerve stimulation.

3. Risks due to radio-frequency (RF) power

The MRI uses RF transmission and reception, at similar frequencies to those used for FM radio. Some of this RF energy is absorbed by the body, and may cause a small temperature rise. The scanner is designed to operate at FDA-approved limits on patient heating. RF can also cause electrically conducting materials such as aluminum foil to heat up, and have caused severe burns to patients.

  • Medication patches may contain aluminum backing, and so should not be worn during the MRI scan
  • Metallic tattoos must be evaluated for safety
  • Extra caution should be exercised in patients with poor temperature regulation

4. Risks due to the use of MRI contrast agents

FDA-approved gadolinium-based contrast agents

Gadolinium contrast agents have been approved for use since the late 1980s. Although these agents can be differentiated on the basis of stability, viscosity, and osmolality, they cannot be differentiated on the basis of efficacy. Gadolinium chelates are extremely well tolerated by the vast majority of patients in whom they are injected. Acute adverse reactions are encountered with a lower frequency than is observed after administration of iodinated contrast media.

When gadolinium-based contrast is being used, subjects need to be screened for possible kidney or liver impairments and excluded appropriately.

Patients who answer yes to the following criteria must have had a blood serum creatinine drawn within 60 days of the MRI scan to determine if gadolinium can be safely administered:

  • Renal disease history (including solitary kidney, renal transplant, renal tumor)
  • Liver disease
  • Age >60
  • History of hypertension
  • History of diabetes

It is the Principal Investigator’s responsibility to obtain the above laboratory values prior to subject’s research scan.

Gadolinium contrast administered to patients with acute renal failure or severe chronic kidney disease can result in a syndrome of nephrogenic systemic fibrosis (NSF).

Nephrogenic systemic fibrosis (NSF) is a fibrosing disease, primarily involving the skin and subcutaneous tissues but also known to involve other organs, such as the lungs, esophagus, heart, and skeletal muscles. Initial symptoms typically include skin thickening and/or pruritis.

Other contrast agents

If your research study involves the use of an investigational agent or an agent other than gadolinium, the risk section must be specific to the agent being studied. Please check with your sponsor or the package insert. Consult with MRI staff if you are unsure about the contrast needs for your research.

5. High risk individuals

Pregnancy

The protocol must state that the risk of MRI to pregnant women and fetuses is currently unknown. Women must be informed of this fact and must take a pregnancy test prior to MRI. The protocol must specify whether female subjects who test positive are not allowed to participate in (1) the study or (2) the MRI component of the study.

Enrollment of Minor Research Subjects

For studies where minors will be scanned, parents/guardians may not have knowledge of the minor subject’s complete health history. For example, minors can consent to certain medical procedures, like requesting birth control procedures, supplies or information. On the other hand, a minor may not have knowledge of their own complete health history, so parents/guardians should not be excluded from the screening process. Extra measures may need to be taken to protect the privacy and confidentiality of these subjects, as well as to obtain a complete medical history. This should be taken into account when designing screening procedures for minors. Additionally, see policy “Pregnancy Testing in Minor Research Subjects.

Common Contraindications to MRI

The magnetic field of the MRI environment has the potential to cause burns or bodily injury if ferrous metal objects are implanted in the body or if personal articles containing ferrous material are brought into the environment. The protocol must specify how participants with contraindications for MRI studies (internal/implanted defibrillator or pacemaker, surgical brain aneurysm clips, cochlear implant, or known metal fragments embedded in the body) will be excluded.

The protocol must specify how participants with medical or electronic devices that may interfere with the scan or pose a risk will be evaluated and how risks to these participants will be minimized. Examples of such devices include but are not limited to:

  • Artificial heart valves;
  • Implanted drug infusion ports;
  • Artificial limbs or metallic joint prostheses;
  • Implanted nerve stimulators;
  • Metal pins, screws, plates, stents or surgical staples.

Incidental Findings

There is a risk that the image will reveal a potentially clinically important finding, but which is beyond the aims of the study. In the event of the confirmation of a significant anomaly, this information will likely be distressing to the subject and constitutes a psychological risk. Additionally, see “Incidental Findings in Neuroimaging Protocols – Detection and Management”

Informed Consent Text

MRI Procedure Section

As part of your participation in this research study, you will have a magnetic resonance imaging (MRI) scan or a functional MRI (fMRI). MRI makes images of your body by using magnetic fields and radiowaves. The MRI exam will take approximately _________ minutes. Prior to your scan, you will be asked to complete a standard safety questionnaire. The purpose of this questionnaire is to ensure that you are able to safely enter the MRI area.

The MRI scan is performed in a special room that houses the MRI system or “scanner”. You will be escorted into the room and asked to lie down on a comfortably padded table that gently glides you into the scanner. The MRI scanner is an upright donut shape with a tube through the middle. The table will move to ensure that the part of your body that we are imaging close to the center of the tube. Even though the tube is open at both ends, some people may feel confined (claustrophobic). If this bothers you, please notify the MRI staff. You will be required to wear earplugs and/or headphones to protect your hearing from the loud tapping, buzzing and beeping noises made as images are being acquired. These loud noises are a normal part of the MRI procedure. The MRI scanner is equipped with an intercom system that allows the MRI staff to communicate with you during the scan. However, while images are being acquired, the noise of the scanner will be too loud for them to hear you. You will be given a squeeze bulb to alert the staff if you become uncomfortable or anxious.

The most important thing for you to do is to relax and lie still. You will be asked to remain as still as possible during the time the imaging takes place, but between sets of images some minor movement may be allowed. The MRI staff will advise you accordingly.

You may end your participation in this study at any time by telling the MRI staff.

Risk Section

The effects of magnetic fields in an MRI scanner have been extensively studied, and there are no known significant risks with an MRI exam. You may, however, be bothered by feelings of confinement (claustrophobia), and by the noise made by the magnet during the procedure. There is a small risk of decreased hearing immediately after an MRI scan. To help lessen this risk, you will be asked to wear earplugs or earphones while in the magnet. Some degree of fatigue or anxiety could occur while undergoing testing. Should this occur, efforts will be made to minimize discomfort.

If contrast is used, explain risks here…example follows: With the IV catheter insertion you may experience discomfort with insertion of the needle and a flushing sensation when the contrast agent is injected. A bruise to the area may develop afterwards.

If gadolinium-based contrast is utilized use the following risk language: The contrast agent you will receive is FDA-approved and used routinely for MRI exams. It contains a material called gadolinium. The injection of contrast may cause discomfort, tingling or warmth in the lips, metallic taste in the mouth, tingling in the arm, nausea, or headache. These symptoms occur in less than 1% (less than 1 in 100) of people and go away quickly.

There is a small risk of an allergic reaction to gadolinium; however, a severe allergic reaction occurs in less than one in 300,000 people.

People with moderate to advanced kidney failure or chronic liver disease are at risk for developing nephrogenic systemic fibrosis (NSF) is a serious progressive disease which causes thickening of the skin and other organs resulting in decreased movement and possibly death. The cause is unknown and not treatable. If you answer yes to the following criteria you will need to have a blood serum creatinine drawn to determine if gadolinium can be safely administered:

Renal disease history (including solitary kidney, renal transplant, renal tumor), liver disease, history of hypertension, history of diabetes and/or if you are of age 60 or older.

If your research study involves the use of an investigational agent or an agent other than gadolinium, the risk section must be specific to the agent being studied. Please check with your sponsor or the package insert. Consult with MRI staff if you are unsure about the contrast needs for your research.

The presence of certain metals or devices in the body may present a risk (due to movement of the metal or mis-operation of the device) if placed in a very strong magnetic field. You may not be allowed to enter the MRI scanner if you have any of the following: cardiac pacemakers or implantable defibrillators, aneurysm clips, neural stimulators, artificial heart valves, ear implants, implanted devices such as insulin pump or drug infusion device, IUDs, magnetic dental appliances, metal fragments or foreign objects in the eyes, skin or body, metal plates, screws and prosthetics, non-removable metal piercings, tattoos on the head and neck, other certain older tattoos with metal containing inks, and permanent makeup (eyeliner). Some medicated patches that are applied to the skin may contain aluminum or other metals. The metal may not be visible. Wearing a patch with a metal backing during a MRI may result in a burn on the skin. You should make the MRI staff aware of any medicated patches that you are wearing prior to your MRI.

If you have other metals in your body, we will need to evaluate your case before you can participate in the study.

There are no known long-term risks associated with MRI scans.

The risk of MRI to pregnant women and fetuses is currently unknown.

Include within the consent, as appropriate, the chance of an incidental finding. Language can be found in the Incidental Findings in Neuroimaging Protocols – Detection and Management.

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20. Investigational Drugs (including Biologics)

Food and Drug Administration (FDA) regulations that govern the use of investigational drugs, devices, or biological products (a biologic is a preparation, such as a drug, a vaccine, or an antitoxin, that is synthesized from living organisms or their products and used as a diagnostic, preventative, or therapeutic agent) in human subjects are substantially similar to the HHS regulations as outlined in these Guidelines. However, they have some requirements for approval, record keeping and reporting that are more rigid than HHS. The FDA audits projects and inspects files, including subject records and, for this reason, subjects must be informed (in the consent form) that FDA may inspect their research records.

Definition of an Investigational Drug

a. A new drug in any of the clinical phases of evaluation which has not been released by the FDA for general use or cleared for sale in interstate commerce.

b. A drug that is commercially available in the U.S. may be considered investigational and require that an investigational new drug (IND) form be filed with the FDA if the proposed use involves a controlled study aimed towards seeking a significant change in the labeling, advertising, route of administration, dosage level, or other factor that affects the risks associated with the use of the product.

c. Drugs which are not on the Hospital Formulary and are to be dispensed within the context of research protocols will also be considered “investigational”.

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20.1 Use of Approved Drugs for Off-Label Indications

Investigational Purposes

If an investigator is using an approved drug in the context of a study protocol (i.e., to gather data for the purpose of changing the drug’s labeling) then the investigation would be subject to IRB review and approval, including informed consent requirements and may also be subject to regulation by the FDA.

Non-Investigational Purposes

If a physician prescribes a marketed drug for an indication not in the approved labeling, s/he has the responsibility to be well informed about the product and to base its use on a firm scientific rationale and on sound medical evidence, and to maintain records of the products and its effects. However, use of a product in this manner as part of the practice of medicine, where no data will be gathered for research purposes, does not require the approval of the IRB.

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20.2 Expanded Access of Investigational Drugs (Compassionate Use)

Expanded access, sometimes referred to as “compassionate use," is the use outside of a clinical trial of an investigational medical product (i.e., one that has not been approved by FDA).

The FDA has an extensive website with information about how to access compassionate use drugs and devices. Wherever possible, use of an investigational medical product by a patient as part of a clinical trial is preferable because clinical trials can generate data that may lead to the approval of products and, consequently, to wider availability. However, when patient enrollment in a clinical trial is not possible (e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials), patients may be able to receive the product, when appropriate, through expanded access.

Requirements for All Expanded Access Uses

Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), a patient may seek individual patient expanded access to investigational products for the diagnosis, monitoring, or treatment of a serious disease or condition if the following conditions are met.

  • The patient and a licensed physician are both willing to participate.
  • The patient's physician determines that there is no comparable or satisfactory therapy available to diagnose, monitor, or treat the patient’s disease or condition.
  • That the probable risk to the person from the investigational product is not greater than the probable risk from the disease or condition.
  • FDA determines that there is sufficient evidence of the safety and effectiveness of the investigational product to support its use in the particular circumstance;
  • FDA determines that providing the investigational product will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval;
  • The sponsor (generally the company developing the investigational product for commercial use) or the clinical investigator (or the patient’s physician in the case of a single patient expanded access request) submits a clinical protocol (a document that describes the treatment plan for the patient) that is consistent with FDA’s statute and applicable regulations for INDs or investigational device exemption applications (IDEs), describing the use of the investigational product; and
  • The patient is unable to obtain the investigational drug under another IND or to participate in a clinical trial.

Also under the FD&C Act statute, a sponsor or a physician may submit a protocol intended to provide widespread access to an investigational product for multiple patients. In this scenario, FDA will permit the investigational product to be made available under a treatment IND if certain criteria are met. 

Ensuring patient safety is a priority - FDA must determine that the potential patient benefit justifies the potential risk of the expanded access use of the investigational drug, and that the potential risk is not unreasonable in the context of the disease or condition to be treated. Even with safeguards, there may be significant unknowns about safety and effectiveness.

Expanded Access Categories

21 CFR part 312 subpart I provides general requirements, describes criteria that must be met to authorize expanded access, lists requirements for expanded access submissions, and describes safeguards that will protect patients and preserve the ability to develop meaningful data about the use of the investigational product.

Under FDA’s current regulations for investigational drugs and biologics, there are three categories of expanded access:

Expanded Access for Individual Patients

  • Individual Patient Expanded Access IND (Single Patient IND)

Access to an investigational drug (including a biologic) for use by a single patient submitted as a protocol under a new IND. The investigational product may or may not be under development. Unless FDA notifies the sponsor that treatment may begin earlier, there is a 30-day waiting period before treatment with the drug may begin.

  • Individual Patient Expanded Access Protocol (also referred to as Single Patient Protocol)

Access to an investigational drug (including a biologic) for use by a single patient submitted as a new protocol to an existing IND by the sponsor of the existing IND.  Typically, several patients may follow the same protocol. The investigational product may or may not be under development.  There is no 30- day waiting period before treatment with the investigational product may begin, but the protocol must be received by FDA and have approval by an Institutional Review Board (IRB) before treatment may begin.

  • Individual Patient Access in an Emergency (also known as emergency expanded access use and emergency access)

Please note that Emergency INDs and protocols are a subset of Individual Patient Access.

(1) Emergency IND: Individual Patient Access IND for Emergency use: Access to an investigational drug (including a biologic) for use by a single patient in an emergency situation (i.e., a situation that requires a patient to be treated before a written submission can be made) submitted as a protocol under a new IND. Treatment is initially requested and authorized by telephone or other rapid means of electronic communication, and may start immediately upon FDA authorization. The written submission (i.e., the individual patient expanded access IND) must be submitted within 15 business days of the telephone authorization.

(2) Emergency Protocol: Individual Patient Expanded Access Protocol for Emergency Use: Access to an investigational drug (including a biologic) for use by a single patient in an emergency situation (i.e., a situation that requires a patient to be treated before a written submission can be made) submitted as a new protocol to an existing IND by the sponsor of the existing IND. Treatment is initially requested and authorized by telephone or other rapid means of communication, and treatment may start immediately upon FDA authorization. The written submission (i.e., the individual patient expanded access protocol) must be submitted within 15 business days of the telephone authorization.
 

In an emergency situation where there is not sufficient time to secure IRB review prior to beginning treatment, the emergency use of the investigational drug must be reported to the IRB within 5 working days, as required under 21 CFR 56.104(c). See additional guidance on Emergency Use of an Investigational Drug or Biologic.

Expanded Access for Intermediate-Size Patient Populations

  • Intermediate-size Patient Population Expanded Access IND

Access to an investigational drug (including a biologic) for use by more than one patient, but generally fewer patients than are treated under a typical treatment IND or protocol, submitted as a protocol under a new IND. The investigational product may or may not be under development for marketing. Unless FDA notifies the sponsor that treatment may begin earlier, there is a 30-day waiting period before treatment may begin.

  • Intermediate-size Patient Population Expanded Access Protocol

Access to an investigational drug (including a biologic) for use by more than one patient, but generally fewer patients than are treated under a typical treatment IND or protocol, submitted as a protocol to an existing IND by the sponsor of the existing IND. The investigational product may or may not be under development for marketing. There is no 30-day waiting period before treatment with the investigational product may begin, but the protocol must be received by FDA and have IRB approval before treatment may begin.

An intermediate-size patient population protocol may also be requested to allow access to treatment with an approved drug (including a biologic) or a related product that is not available through marketing channels because of failure to meet the conditions of approval or a drug shortage, provided the drug and the patient meet the general criteria for expanded access as well as the criteria specific to use in an intermediate-size patient population.

Expanded Access for Widespread Use

  • Treatment IND:

Access to an investigational drug (including a biologic) for treatment use by a large (widespread) population, submitted as a protocol under a new IND. The investigational product must be under active development for marketing. Unless FDA notifies the sponsor that treatment may begin earlier, there is a 30-day waiting period before treatment may begin.

  • Treatment Protocol:

Access to an investigational drug (including a biologic) for treatment use by a large (widespread) population, submitted as a protocol to an existing IND by the sponsor of the existing IND. The investigational product must be under development for marketing. Unlike other access protocols submitted to existing INDs, there is a 30-day waiting period before treatment may begin, unless FDA notifies the sponsor that treatment may begin earlier.

Consider Investigational Product Availability and Costs

  • The medical product company must agree to provide the investigational drug for expanded access use. FDA cannot require a company to provide an investigational drug for expanded access use to proceed.
  • A company may decide to turn down a request if, for example it is not able or willing to provide access to an investigational drug outside of clinical trials intended to support marketing approval.
  • In some cases, patients may have to pay (PDF) for using the investigational drug and/or for medical care associated with the use of the investigational drug. In others, pharmaceutical companies may elect not to charge.

IRB Review

If a researcher wishes to treat a patient who is eligible to receive an expanded access investigational drug, the IRB must be notified immediately. The IRB will need to know under which category the use falls (individual, intermediate, or widespread as listed above), the timeline for treatment, and be provided with a protocol (which can be from the sponsor or investigator written), a consent (which can be developed from either the sponsor template or the IRB template), completion of the appropriate FDA IND submission forms and the IND application number if the PI has obtained it already. At time of continuing review, the PI must provide the IRB committee with a copy of the annual update to the FDA on the patient as well as completing the continuing review forms.

To Allow for IRB Chairperson Concurrence (versus convened meeting) for an Individual Patient IND

Having trouble viewing Form FDA 3926 in the browser? Download the form and open with Adobe to complete.

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A physician submitting an individual patient expanded access IND using PDF icon Form FDA 3926 (PDF), may select the appropriate box on that form to request authorization to obtain concurrence by the IRB chairperson or by a designated IRB member before the treatment use begins, in lieu of obtaining IRB review and approval at a convened IRB meeting at which a majority of the members are present. In order to utilize the expedited Chair review process, PI’s must complete PDF icon Form FDA 3926 (PDF) and check box 10.b. under 21 CFR 56.105. 

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21. Investigational Devices

Definition of an Investigational Device

Investigational devices are medical devices which are the object of clinical research to determine their safety or effectiveness. Studies undertaken to develop safety and effectiveness data for medical devices involving human subjects must be conducted according to the requirements of the Investigational Device Exemption (IDE) regulations (21 CFR 812). Investigational devices are classified as either significant risk or non-significant risk devices.

Non-Significant Risk Device

A non-significant risk device is one that does not present a potential for serious risk to the health, safety, or welfare of the subject. Examples of non-significant risk devices are: most daily wear contact lenses, lens solutions, heel cups, antibacterial surgical garments, incontinence devices, oral training splints, and ultrasonic tooth cleaners.

Unless otherwise notified by FDA, an investigation of a non-significant risk device is considered to have an approved IDE if the sponsor fulfills the abbreviated requirements of the IDE regulations. Prior IRB approval is required.

Significant Risk Device

A significant risk device is one that presents a potential for serious risk to the health, safety, or welfare of the subject. Such a device is intended as an implant; is to be used in supporting or sustaining human life; or is of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health. Examples of significant risk devices are catheters (other than urological), ventilators, CPR devices, TMJ prostheses, stents, lithotripters, sutures and absorbable bandages/materials, ECT devices, extended wear contact lenses, pacemakers, contraceptive devices, most laser systems, and most hemodialysis systems.

Investigations involving significant risk devices must meet the full IDE requirements including the submission of an IDE application to the FDA. Prior IRB approval is required.

IRB Review of Investigational Device Protocols

It is the responsibility of the IRB to determine which device studies pose significant risk or non-significant risk when the studies do not have an Investigational Device Exemption.

In deciding if a device presents significant or non-significant risks, the IRB will consider the device’s total risks, and not compare these with the risks of alternative devices or procedures. If the device is used in conjunction with a procedure involving risk, the IRB will consider the risks of the procedure in conjunction with the risks of the device. Once a decision on the degree of risk is reached, the IRB will consider whether the study should be approved or not.

Some studies involving non-significant risk devices may also be considered minimal risk studies and thus may be reviewed through the expedited review procedure established by the IRB.

FDA considers studies of all significant risk devices to present more than minimal risk; thus, IRB review at a convened meeting is required for all studies involving significant risk devices. In considering whether a study should be approved, the IRB will use the same criteria it would use in considering approval of any research involving an FDA-regulated product. The IRB will consider the risks and benefits of the test medical device compared to the risks and benefits of alternative devices or procedures in deciding the approvability of a study.

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21.1. Expanded Access of Investigational Devices

When a patient has a serious or life-threatening condition that is not addressed by current approved treatments, options may exist to use an investigational medical device (i.e., one that has not been approved or cleared by FDA) to treat the patient.

Normally, such investigational devices with significant risks may only be used on human subjects through an FDA-approved clinical trial for which an investigational device exemption (IDE) allows the investigational device to be used in a clinical study. However, there are circumstances under which a health care provider may use an investigational device outside of a clinical study to save the life of a patient or to help a patient suffering from a serious disease or condition for which no other alternative therapy exists.

The use of an investigational device outside of a clinical trial for treatment of a patient is called “expanded access.”  If enrollment in an existing clinical trial protocol is not possible (e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials to address the patient’s condition), patients/physicians have the potential to receive expanded access to investigational devices under one of three alternative mechanisms: emergency use, expanded access use, and treatment use. The FDA has an extensive website with information on process and how to apply.

Emergency Use

Emergency use is the use of an investigational device in an emergency situation. It is intended to provide patients and physicians with access to devices intended to treat life-threatening or serious diseases or conditions when there is no available alternative and no time to obtain FDA approval. Criteria for emergency use are:

  • The patient has a life-threatening or serious disease or condition that needs immediate treatment;
  • No generally acceptable alternative treatment for the conditions exists; and
  • Because of the immediate need to use the device, there is no time to use existing procedures to obtain FDA approval for the use.

See Emergency Use of an Investigational Drug or Biologic or Investigation Device section for information regarding process for informing the IRB.

Expanded Access Use

FDA recognizes that there are circumstances in which an investigational device is the only option available for a patient faced with a serious or life-threatening disease or condition.

The use provision provides a path to accessing investigational devices that have not received FDA approval or clearance for patients for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. use can be for devices that are being studied in a clinical trial under an IDE for patients who do not meet the requirements for inclusion in the clinical investigation but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. It can also be used for devices that are not being studied in a clinical investigation (i.e., an IDE for the device does not exist). This provision is typically approved for individual patients but may be approved to treat a small group. Criteria for compassionate use are:

  • The patient has a life-threatening or serious disease or condition; and

No generally acceptable alternative treatment for the condition exists.

Prior full committee IRB review and approval is required.

Treatment Use

An approved IDE specifies the maximum number of clinical sites and the maximum number of human subjects that may be enrolled in the study. During the course of the clinical trial, if the data suggest that the device is effective, then the trial may be expanded to include additional patients with life-threatening or serious diseases. This is called treatment use. Criteria for treatment use are:

  • The device is intended to treat or diagnose a serious or immediately life-threatening disease or condition;
  • There is no comparable or satisfactory alternative device available to treat or diagnose the disease or condition in the intended patient population;
  • The device is under investigation in a controlled clinical trial for the same use under an approved IDE, or all clinical trials have been completed; and
  • The sponsor of the controlled clinical trial is pursuing marketing approval/clearance of the investigational device with due diligence.

Prior full committee IRB review and approval is required.

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22. Humanitarian Device Use (HUD)

The Humanitarian Use Device or HUD program was established in 1990 with passage of the Safe Medical Devices Act and creates an alternative pathway for getting market approval for medical devices that may help people with rare diseases or conditions. As defined by 21 CFR 814.3(n), and updated by the 21st Century Cures Act 2016, a HUD is a “medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year.” 

The regulation provides for the submission of a humanitarian device exemption (HDE) application, which is similar in both form and content to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of a PMA.

An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The application, however, must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. Additionally, the applicant must demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.

An approved HDE authorizes marketing of the HUD. However, a HUD may only be used after IRB approval has been obtained for the use of the device for the FDA approved indication. The labeling for an HUD must state that the device is a humanitarian use device and that, although the device is authorized by Federal Law, the effectiveness of the device for the specific indication has not been demonstrated.

Initial and Continuing Review

Initial proposed use of the humanitarian use device must be reviewed and approved at a convened meeting of the IRB, in accordance with 21 CFR 56.111.

FDA recommends the use of an expedited procedure for subsequent continuing reviews because a HUD is a legally marketed device and no safety and effectiveness information is being collected systematically, as is required for a research protocol.

Consent

Prospective consent is not always attainable or necessarily in the best interest of the patient in these cases.  Often, the use of the particular HUD is not anticipated yet does not meet the criteria for an “Emergency Use” either. FDA regulations and guidance leave it to the discretion of the local IRB whether or not to require prospective written consent.

Given the complexity of obtaining prospective consent in these situations, the Committee does not require written consent for HUD protocols. Physicians should document consent in the medical chart whenever possible.

Reporting/Administrative Requirements

1. Submit any proposed changes to the protocol for approval prior to initiation.

2. Report adverse events and unanticipated problems to subjects or others related to the use of the device to the IRB and the sponsor in accordance with FDA regulations and UVM/UVM Medical Center Adverse Event and Unanticipated Problems Reporting Policy and Procedures.

3. Complete and submit continuing review forms as requested (at least once annually). Attach a copy of the current FDA-approved product labeling for the HUD.

Using HUDs in Compassionate Use Situations

If a HUD is used outside its approved indication(s), FDA recommends that the physician obtain informed consent from the patient and ensure that reasonable patient protection measures are followed, such as devising schedules to monitor the patient, taking into consideration the patient's specific needs and the limited information available about the risks and benefits of the device. FDA further recommends that the physician submit a follow-up report on the patient’s condition to the HDE holder.

In such circumstances, the physician shall, after the use of the device, notify the Committee of the use within five working days. The date on which the device was used, along with the reason for the use should be reported using the “Unanticipated Problem Potentially Involving Risk…” form.

Using HUDs in Emergency Use Situations

If a HUD is used in an emergency situation and consent is unable to be obtained then the Committee’s policy on waiver of consent for emergency use is applied.

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23. Emergency Use of an Investigational Drug or Biologic or Investigation Device

Emergency use is defined as the use of a test article (investigational drug or biological product or investigational device) on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval." 21 CFR 56.102(d)

Generally, IRB approval is required prior to conducting human subject research. However, an exception to this is the one-time use of an investigational drug or device (test article) for a single participant in a life-threatening (emergency use) situation.

An emergency use of a test article is exempt from prior IRB review and approval, provided that the emergency use of a test article is reported to the IRB within 5 working days of the date of the emergency use.

Any subsequent use of the test article at UVM is subject to IRB review and approval.  Only one emergency use of the test article is permitted  and  any  subsequent use needs to be done under an IRB approved protocol.  However , the FDA acknowledges that it would be inappropriate to deny emergency treatment to a second individual if the only obstacle is that the IRB has not had sufficient time to convene a meeting to review the issue. (FDA Information Sheet, 2003 Update)

The IRB Chair or designated IRB member will review the submission of Emergency Use of an Investigational Drug, Biologic, or Device Certification of Compliance Form  (DOCX) in support of an emergency use of a test article.

Criteria for Emergency Use

All the following must be satisfied

  • Existence of a life-threatening/severely debilitating condition where no standard acceptable treatment is available
  • No current IRB approved protocol covering the situation and no time to obtain prior FDA and IRB approval
  • Availability of an investigational agent or device which in the opinion of the physician might be beneficial, and
  • Availability of an investigational agent or device from a sponsor or elsewhere.
  • The Emergency Use of a Test Article is  not  a systematic investigation designed to develop or contribute to generalizable knowledge.

If the proposed use meets this definition, the investigator must contact the IRB office to request concurrence with administration of the test article.

During Normal Business Hours

Contact the RPO Office at 656-5040

Outside Normal Business Hours Use Provider Access System to Contact One of the Chairs

David Kaminsky, M.D., CHRMS Chair

Alan Homans, M.D., CHRMS Executive Chair

Consent Requirement

The process of informed consent must meet FDA requirements [21 CFR 50.25]. The investigator is required to obtain legally effective informed consent of the subject or the subject’s legally authorized representative, using an appropriate consent document. Whenever possible, a copy of the consent form to be used is requested in advance (generally a standard form exists and the IRB does not require that it be put into the usual institutional format for an emergency use). The IRB has a consent template located on its forms page for use.

Exception from Informed Consent Requirement

Informed consent of the subject or the subject’s legally authorized representative is required, unless both the investigator and a physician (not otherwise participating in the investigation) certify in writing  that:

  1. the patient is confronted with a life-threatening situation;
  2. informed consent cannot be obtained from the patient (because patient cannot communicate or is incompetent to give consent);
  3. consent cannot be obtained from the legally authorized representative (unavailable or unknown); and
  4. no alternative approved treatment/therapy is available that provides an equal or greater likelihood of saving the patient’s life. (21 CFR 50.23(2)).

Emergency Use with Drugs and Biologics

The investigator must submit the following materials to the IRB within five (5) working days, following the use of the test article:

  • information about the patient
  • indication of the life-threatening or severely debilitating nature of the situation
  • explanation as to why this drug or treatment was necessary
  • and , if the emergency use occurred  without obtaining prior informed consent Section D  on this form must also be completed: Independent Physician Certification - Emergency Use of a Test Article Without Informed Consent
  • Written permission from the manufacturer for the use of the test article under their IND.  Generally the investigator will contact the manufacturer and determine if the drug or biologic can be made available for the emergency use under the company’s IND. If the company only allows cross-referencing to their IND, declines permission or cannot be reached, the investigator should contact the FDA for authorization of the shipment of the drug in advance of the IND submission. In such a case the FDA may authorize shipment of the test article in advance of the IND submission. The IRB will request that the investigator contact the FDA to obtain an Emergency Use IND.
  • A copy of the signed Consent Form.

Emergency Use with Devices

The investigator must submit the following materials to the IRB within five (5) working days following the procedure:

  • information about the patient
  • indication of the life-threatening or severely debilitating nature of the situation
  • explanation as to why this device was necessary
  • and,  if the emergency use occurred  without obtaining prior informed consent Section D  on this form must also be completed: Independent Physician Certification - Emergency Use of a Test Article Without Informed Consent
  • Written permission from the manufacturer for the use of the test article under their IDE. Generally the investigator will contact the manufacturer and determine if the device can be made available for the emergency use under the company’s IDE. The IRB will request that the investigator contact the FDA to obtain an IDE. If the company only allows cross-referencing to their IDE, declines permission or cannot be reached or an IDE does not exist, the FDA expects the investigator to:
    • Determine whether the criteria for emergency use have been met;
    • Assess the potential for benefits from the unapproved device and to have substantial reason to believe that benefits exist;
    • Assure that the decision of the investigator that an emergency exists is not based solely on the expectation that IDE approval procedures may require more time than is available.
    • Obtain an independent assessment by an uninvolved physician.

In addition, if the device is used and  there is no IDE :

  • The use must be reported to the FDA within 5 working days (to CDRH). This report should contain a summary of the conditions constituting the emergency, patient outcome information, and the patient protection measures that were followed.
  • Copy of signed Consent Form.

FDA Emergency use requests

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24. Subjects Vulnerable to Coercion or Undue Influence

If there is a possibility that any group of research subjects may be vulnerable to injury, coercion or undue influence, the investigator should include additional safeguards in the consent process and protocol that attempt to minimize, to the greatest extent possible given the specific research, those risks. The special populations for which there are currently additional federal regulations providing additional protections are:

Pregnant Women, Fetuses and Neonates;

Prisoners; and

Children.

Additional populations not currently specifically covered by federal regulations but for which additional unspecified safeguards could be required by the IRB, are listed below.

1. Economically disadvantaged subjects;

2. Students;

3. Subjects with HIV;

4. Adult Subjects Lacking Capacity to Consent (including, but not limited to the following);

  • Dementia (including Alzheimer’s)
  • Anxiety disorders
  • Depression
  • Obsessive / compulsive disorders
  • Manic / bipolar disorders
  • Personality disorders
  • Mental retardation
  • Psychoses

5. Subjects with drug and/or alcohol addictions (certificates of confidentiality are strongly recommended for this group);

6. Subjects with other disabilities; or

7. Non-English speaking subjects.

Depending on the research, exclusion of any of the above populations might be construed as unfair and attempts should be made to include these populations, with appropriate protections, if they are applicable to the research question. If the protocol is records or specimen collection only and the vulnerable population cannot be identified or there is no risk to the vulnerable subject they should not be listed as targeted subjects on your protocol cover form.

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24.1 Pregnant Women, Fetuses, Neonates of Uncertain Viability and Non-Viable Neonates 45 CFR 46 Subpart B

Pregnant Women or Fetuses may be involved in research if all of the following conditions are met:

1. Preclinical studies (studies on pregnant animals, and clinical studies, including studies on non-pregnant women), have been conducted and provide data for assessing potential risks to fetuses, if appropriate;

2. If there is the prospect of direct benefit for the fetus; the risk to the fetus is caused solely by interventions or procedures;

3. If there is no prospect of benefit for the fetus; the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;

4. Any risk is the least possible for achieving the objectives of the research;

5. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;

6. Researchers will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and

7. Researchers will have no part in determining the viability of a neonate.

Consent: The consent of the pregnant woman and the father should be obtained in accordance with normal informed consent processes. Individuals providing consent should be fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate.

The father's informed consent is not required if:

1. The purpose of the activity is to meet the health needs of the mother (direct benefit to the mother); OR

2. The purpose of the activity is to meet the health needs of the mother and fetus (direct benefit to the mother and fetus); OR

3. When risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means; OR

4. He is unavailable; OR

5. His competency is in question; OR

6. He is temporarily incapacitated; OR

7. The pregnancy resulted from rape or incest.

The father’s informed consent should be secured when:

1. The purpose of the activity is to meet the health needs of the fetus (direct benefit to the fetus) only.

For children who are pregnant (less than 18 yo) assent and permission should be obtained in accord with normal procedures for children.

Neonates of uncertain viability may be involved in research if all of the following conditions are met:

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.

2. Researchers engaged in the research will have no part in determining the viability of a neonate.

3. The IRB determines that:

a) The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or

b) The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research.

Consent Regarding Neonates of Uncertain Viability:

1. Informed consent can be obtained from either parent of the neonate. If neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of either of the parents’ legally authorized representatives should be obtained. If the pregnancy resulted from rape or incest, consent need not be obtained from the father nor his legally authorized representative;

2. Each individual providing consent must be fully informed regarding the reasonably foreseeable impact of the research on the neonate.

Nonviable neonates may be involved in research if all of the following conditions are met:

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates;

2. Researchers engaged in the research will have no part in determining the viability of a neonate;

3. Vital functions of the neonate will not be artificially maintained;

4. The research will not terminate the heartbeat or respiration of the neonate;

5. There will be no added risk to the neonate resulting from the research; and

6. The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means.

Consent Regarding Nonviable neonates:

1. Informed consent must be obtained from both parents of the neonate. In some cases a waiver and/or alteration of consent is applicable, see Sec. 46.116(c) and (d). However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements. If the pregnancy resulted from rape or incest, consent need not be obtained from the father. Informed consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements for consent; and

2. Each individual providing consent must be fully informed regarding the reasonably foreseeable impact of the research on the neonate.

Viable neonates. A neonate, after delivery, that has been determined to be viable may be included in research only in accordance with the policies for including children in research (see children below).

Consent for viable neonates. See section on Children.

Research involving, after delivery, the placenta, the dead fetus or fetal material.

Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.

If information associated with material described in this section is recorded for research purposes in a manner that individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent regulations are applicable.

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24.2 Prisoners

Consult 45 CFR 46 Subpart C (Sections 301, 302, 303, 304, 305 and 306)

Prisoners as defined by HHS regulations are any individuals involuntarily confined, detained, or incarcerated in a penal institution or other alternative facility (by virtue of statuses or commitment procedures) and individuals detained pending arraignment, trial, or sentencing.

OHRP does not automatically consider a person under a court order to be a “prisoner” under Subpart C. Study participants on parole or probation are NOT considered to be prisoners under Subpart C. Persons in post-release criminal justice halfway houses are presumptively NOT considered by OHRP to fit the Subpart C definition of prisoners. This is dependent upon whether detainment or confinement is voluntary.

The only categories of research permitted with prisoners are:

1) Study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;

2) Study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;

3) Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction and sexual assaults) provided that the study may proceed only after the Secretary of Health and Human Services (HHS) has consulted with appropriate experts including experts in penology, medicine and ethics, and published notice in the Federal Register of his intent to approve such research;

4) Research on practices, both innovative and accepted, that have the intent and reasonable probability of improving the health or well-being of the subject. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups that may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine and ethics, and published notice in the Federal Register of his intent to approve such research.

The IRB must make the following findings during its review in order to approve the research:

1) Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;

2) The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;

3) The procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless you provide to the IRB justification in writing for allowing some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;

4) The information is presented in language that is understandable to the participant population;

5) Adequate assurance exists that parole boards will not take into account a prisoner’s participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and

6) Where the IRB finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners’ sentences, and for informing participants of this fact.

What happens if a human subject becomes a prisoner during the course of a research study?

If a human subject involved in ongoing research becomes a prisoner during the course of the study, and the relevant research proposal was not reviewed and approved by the IRB in accordance with the requirements for research involving prisoners under subpart C of 45 CFR part 46, the investigator must promptly notify the IRB. All research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-subject must be suspended immediately, except as noted below. Upon receipt of the investigator's report that a previously enrolled research subject has become a prisoner, if the investigator wishes to have the prisoner subject continue to participate in the research, the IRB must promptly re-review the proposal in accordance with the requirements of subpart C, and the institution(s) engaged in the research involving the prisoner subject must send a certification to OHRP and wait for a letter of authorization in reply when federal funds support the research. Otherwise, the prisoner subject must stop participating in the research, except as noted below.

OHRP allows one important exception to the requirement that all research interactions or interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-subject must cease until the regulatory requirements for research involving prisoners are met. In special circumstances in which the investigator asserts that it is in the best interests of the subject to remain in the research study while incarcerated, the subject may continue to participate in the research until the requirements of subpart C are satisfied. The investigator must promptly notify the IRB of this occurrence, so that the IRB can re-review the study. Note that in these circumstances, some of the findings required by 45 CFR 46.305(a) may not be applicable; for example, the finding required under 45 CFR 46.305(a)(4) regarding the selection of subjects within the prison may not be applicable, if the subject was recruited outside of an incarcerated context. The IRB will need to document findings of non-applicability accordingly.

When preparing for an amendment to your protocol to request the continuation of a research subject who has become a prisoner, it is unlikely that previous review of the research and the consent document contemplated the constraints imposed by incarceration. In this case, an amendment that includes appropriate justification (benefits to the individual outweigh the additional risks due to incarceration) should be written including specific examples of benefits to the individual prisoner-subject. As part of the submission a consent addendum that the now prisoner-subject will need to sign in addition to the original consent must also be submitted for review and approval.

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24.3 Children

Research that is allowable with children is determined by the degree of risk involved. These categories of allowable research are:

1) No greater than minimal risk where adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians.

2) Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects, if the IRB finds that:

a. The risk is justified by the anticipated benefits to the subjects;

b. The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; AND,

c. Adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

3) Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition, if the IRB finds that:

a. The risk represents a minor increase over minimal risk;

b. The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social or educational situations;

c. The intervention or procedure is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance for the understanding or amelioration of the subject's disorder or condition; AND

d. Adequate provisions are made for soliciting assent of the children and permission of the parents or guardians.

4) Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children if:

a. The IRB finds the above to be true; AND

b. The Secretary of HHS, after consultation with a panel of experts in pertinent disciplines has determined:

1. The research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children is present;

2. the research will be conducted in accordance with sound ethical principles;

3. adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

NOTE: The regulations define Minimal Risk as the risks of harm anticipated in the proposed research are not greater, considering the probability and magnitude, than ordinarily encountered in the daily life of the research subject, or during the performance of routine physical or psychological examinations or tests. Physical, psychological, social, legal or other risks should be assessed/considered.

Children Who Are in State Custody

Children who are wards of the State or any other agency, institution, or entity may be included in research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition, only if such research is:

  1. Related to their status as ward; or
  2. Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

If the research meets the condition(s) above, an advocate should be appointed for each child who is a ward (one individual may serve as advocate for more than one child), in addition to any other individual acting on behalf of the child as legal guardian or in loco parentis.

The advocate should be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child’s participation in the research and who is not associated in any way (except in the role as advocate) with the research, the investigators, or the guardian organization. The advocate does not provide informed consent, that is only provided by the legal guardian as determined by DCF.

For guidance on consenting children, see the section on consenting children.

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24.4 Non-English Speaking Individuals Participating in Research

The Department of Health and Human Services (DHHS) regulations for the protection of human subjects require that informed consent information be presented in "language understandable to the subject," and, in most situations, that informed consent be documented in writing (45 CFR §46.116 and §46.117).

Steps must be taken to assure true informed consent is obtained when non-English speaking individuals are being approached for research participation. This does not simply mean that a form is signed, but rather that steps are taken to assure the study and voluntary nature of the research is understood by the subject. A translator may need to be involved in the informed consent discussion and a translated consent document may be needed. Further, the IRB may require the investigator to submit a back-translation of the informed consent.

If the majority of subjects are expected to be non-English speaking, use of the Long Form Consent and Authorization Process is required.

If the protocol is already approved for English speaking subjects and a non-English speaking subject presents for participation, the Oral Translation with Short Form Consent Process and Authorization Process may be used. To do this, researchers must submit an amendment to include a non-English speaking individual as a subject addressing all of the requirements listed in that section.

For information regarding the consent process of this population, See the section n Informed Consent and HIPAA Authorization Process for Non-English Speaking Individuals.

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25. Pregnancy Testing in Minor Research Subjects

A minor is defined as a person under the legal age of full responsibility. All persons under 18 years of age are considered minors. Research involving minors requires special consideration on the part of both the research team as well as the IRB.  This is particularly so if the study requires pregnancy testing of minor subjects, either to confirm eligibility or as part of routine safety monitoring, for example, before the administration of study drug.  Researchers must consider how results of such tests will be handled and to whom they will be disclosed.  This plan must be clearly outlined in the protocol as well as in any consent and assent documents.

Pregnancy Testing Requirement

Any protocols that utilize UVM Medical Center resources, would require point-of-care pregnancy testing. UVM Medical Center staff should refer to UVM Medical Center Policies and Procedures Labpoct 110.21 for information about those procedures. There is no pregnancy testing policy for protocols that only utilize UVM resources.

Plan for Disclosure of Pregnancy

If pregnancy is an exclusion criterion and screening procedures to determine eligibility require a pregnancy test, the researcher must determine whether the results of screening tests will be disclosed to the minor subject’s parent(s)/legal guardian or only to the minor subject.  There are factors that may necessitate disclosure to parents even for a screening pregnancy test, or that may make reporting to parents after enrollment inappropriate.  Researchers may consider both the age and maturity of the minor subjects, as well as any other factors that may impact the reporting decision, such as developmental delays or other relevant physical or mental characteristics of the subject population being studied.  For example, if a researcher is enrolling autistic subjects, a positive pregnancy test in this population, regardless of age, would almost certainly need to be disclosed to the parents whether it was a screening test or not.  On the other hand, a pregnancy in a 17-year old participating in a study for which parental permission was waived (see section 11.D. Children, Waiver of Consent would not necessarily need to be reported to parents.

Reporting Pregnancy of a Minor to Authorities

Researchers should be aware that there is no age specified at which point the researcher becomes required to report the pregnancy of a minor under state law.  Pregnancy of a minor does not necessarily indicate suspected abuse and many other factors may need to be considered. Researchers may consider both the age and maturity of the minor subjects, as well as any other factors that may impact the reporting decision, such as developmental delays or other relevant physical or mental characteristics of the subject population being studied.  State child abuse laws governing healthcare providers or persons receiving information about a child who has received healthcare services outline when mandatory reporting is required. See Appendix N. Exceptions to Confidentiality.

Language in Consent Form

Regardless of the specifics of the reporting plan, both the parental consent form and the minor’s assent form (they may be the same form depending on the age of the minor subjects) should clearly outline when pregnancy tests will be performed, to whom the results will be disclosed, and whether there may be any exceptions to this. Additionally, an exception to confidentiality statement must be included when it is possible that suspected child abuse or neglect be revealed, requiring mandatory reporting to regulatory authorities.

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26. Human Subject Research Monitoring Program

The IRB has developed a system for monitoring on-going research to ensure congruence with the IRB-approved protocol and compliance with applicable human subject protection guidelines and regulations. The IRB is committed to administering a process that is educational for the personnel involved in the human subjects research, with the goal of fostering a collegial environment, and thus contributing to a culture of compliance.

Our monitoring program covers a sampling of all studies that are currently active. Highest priority is given to investigator-initiated studies that do not have other formal monitoring processes in place.

The monitoring process may include representatives from other institutional entities which oversee the specific protocol to be monitored. The IRB is currently collaborating with the University of Vermont Cancer Center (UVMCC) and with the Research Subject Advocate (RSA) Office of the Clinical Research Center (CRC).

The monitoring process includes a review to determine that:

1. the protocol on file with the IRB is the protocol being used and being followed;

2. all modifications have been submitted to and approved by the IRB and have been implemented;

3. the consent document being used is that which was approved by the IRB;

4. the consent forms are appropriately signed and dated; and

5. adverse event and unanticipated problem reporting guidelines are being followed.

Monitors:

- IRB Staff

- Others as necessary, i.e., IRB Chair, IRB Administrator, or other IRB member

- When appropriate, representative(s) from collaborating units, i.e., CRC RSA Office or UVMCC

Notice:

- Investigator will be given advance notice of the monitoring visit and a list of studies to be reviewed.

- A representative number of subject research files will be reviewed. Copies of any documents reviewed at the site visit may be requested at that time.

- Investigator and/or designee should be prepared to answer questions about the timing of procedures for the specific subjects identified.

Review:

Data will be reviewed to determine whether: 1) the signed consent forms were the correct version; 2) the date of informed consent corresponds with date of procedures; 3) approved protocol is being used; 4) amendments were approved and are being followed; 5) adverse reactions and unanticipated problems were reported according to IRB policy; and 6) other items deemed appropriate for review during collaborative monitoring visits are in compliance.

Possible Outcomes:

An immediate exit interview will be conducted with the principal investigator or his/her designee. After a preliminary report has been reviewed internally, a final report will be forwarded to the principal investigator. Categories of possible monitoring outcomes are as follows:

- Acceptable;

- Additional action required by Investigator; or

- Further Committee review required.

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27. Noncompliance Policy and Procedures

It is the responsibility of the Committees on Human Research (also referred to as CHRMS, CHRBSS, the Committee(s), or the IRB(s)), in accordance with the Federal-Wide Assurances between UVM/UVM Medical Center and the Department of Health and Human Services Office of Human Research Protections (OHRP), to investigate and review possible noncompliance; develop and ensure implementation of appropriate corrective actions; and ensure required reporting of any serious and/or continuing noncompliance. In all cases of noncompliance, the IRBs must assess the level of risk of harm, determine whether the research may safely continue, and specify those conditions necessary for the continued protection of human subjects. This document describes the procedures for handling these matters. This policy is not all encompassing, and the IRB reserves the right to use its discretion in individual cases.

Definitions

Noncompliance is defined as the conduct of research in a manner that deviates from the approved protocol or disregards or violates federal regulations or institutional policies and procedures applicable to human subjects research. Noncompliance may result from actions or omissions by study personnel, and can range from relatively minor or technical deviations to serious deviations that threaten subjects’ rights or welfare.

Serious Noncompliance is defined as noncompliance that, in the judgement of the IRB, potentially increases the risk of harm to research subjects, reduces benefits to human subjects, or compromises the integrity of the research oversight process.

Continuing Noncompliance is defined as a pattern of noncompliance (recurring or ongoing) that, in the judgement of the IRB, may indicate an underlying deficiency in knowledge of the regulations or IRB requirements or an unwillingness or inability to comply with these regulations/requirements.

General Noncompliance Review Procedures

The investigation of potential noncompliance begins when the IRB becomes aware of potential noncompliance. This may include an allegation (unproved assertion) of noncompliance, a self-disclosure of noncompliance, or any other indication that noncompliance may have occurred. The process for the review of potential noncompliance involves initial administrative review, followed by an inquiry/fact finding process if indicated. Once complete, the IRB makes a determination as to whether the noncompliance is serious, continuing, or neither. The IRB determination will be documented in a summary report that contains a corrective action plan in cases of serious or continuing noncompliance. This process is detailed below, however at any point in the review process, the IRB designee may at their discretion:

  • Recommend intervention for the safety of the research subjects
  • Recommend the suspension of research activities
  • Inform, involve, and/or provide salient documents to the PI, members of the research team, the Department Chair, Dean, legal counsel, or Institutional Officials, as appropriate
  • Initiate reporting per federal regulations
  • Initiate a monitoring visit
  • Recommend immediate corrective actions

Process of Noncompliance Review and Determination

Initial Review of Allegation or Indication of Noncompliance: When there is an allegation or indication of noncompliance, the first step is an administrative review to determine if, in the judgement of the person(s) conducting the review, there is the potential for serious or continuing noncompliance. The initial review may be conducted by the RPO Director, RPO Assistant Director(s), an IRB Chair (Executive Chair, Associate Chair, or Chair), or another Institutional Representative. Allegations/indications which are determined to have no potential to be serious and/or continuing noncompliance are resolved with either no follow-up (i.e. when an allegation or indication has no merit) or directly with the PI.

Inquiry/Fact Finding Process: If it is determined that the noncompliance has the potential to be serious or continuing or if questions remain following the initial review, then an inquiry (fact finding) process will begin. The particular circumstances of the noncompliance will determine when the fact finding begins and when the committee is briefed. The fact finding may be conducted by any IRB designee including a sub-committee or subcommittee member, the RPO Director, Assistant Director(s), an IRB Chair (Executive Chair, Associate Chair, or Chair) or other Institutional Representatives. The IRB may be briefed at any point throughout the fact finding process, as deemed appropriate by the designee. The fact finding process continues until the designee has arrived at a recommendation of determination (i.e. serious noncompliance and/or continuing noncompliance, or neither). A fact finding report is then prepared and includes the recommendation of determination and draft corrective actions. This fact finding report will be shared with the PI, and if applicable, other person(s) involved. All parties will be provided an opportunity to respond to any factual inaccuracies within the report before the committee deliberates.

Deliberation by the IRB: At a convened meeting, the IRB will consider all available information and make a determination as to whether the fact finding revealed serious noncompliance and/or continuing noncompliance, or neither. The following factors will be taken into consideration by the IRB or designee in making their initial determination as to whether the noncompliance is serious and/or continuing noncompliance. As each situation is unique, the indicators of noncompliance that are important in one case may not be relevant in other cases.

Factors in the Determination of Serious Noncompliance:

  • Level of risk or potential risk to subjects
  • Severity of violation of the research process
  • Frequency or number of minor deviations or errors
  • Intent
  • Threat to integrity of the IRB review processes and requirements for the protection of human subjects (i.e. falsification of IRB documents)
  • Other factors that, in the judgement of the IRB or designee, are relevant to the situation being reviewed.

Factors in the Determination of Continuing Noncompliance:

  • Similarity of noncompliance to previous deviations and/or noncompliance within the same protocol.
  • Similarity of noncompliance to previous deviations and/or noncompliance in other protocols conducted by the investigator.
  • Likelihood that instances of noncompliance will continue without intervention

Final Determination of the IRB: If, in the judgement of the committee, the noncompliance is neither serious nor continuing, this determination will be shared with the PI. If, in the judgement of the committee, the noncompliance is serious and/or continuing. The designee will prepare a summary report including the IRB’s determination and an approved corrective action plan. This report will be shared with the PI, who will be given 14 days to review it before it becomes final.

Development of Corrective Action Plans:

The IRB/designee will develop a proposed plan for corrective actions based on the information gathered during fact-finding and input from the principal investigator and/or other affected individuals. The proposed plan may:

  • Require no further action
  • Require minor corrective actions to achieve compliance
  • Institute limitations on the use of data
  • Require additional education
  • Require the investigator and/or other affected individuals to develop and implement procedures to prevent recurrence
  • Review internal departmental or institutional mechanisms and systems for opportunities to prevent recurrence or similar occurrences by others
  • Require additional oversight (e.g., by other faculty member or department process)
  • Require more frequent IRB reviews
  • Require internal monitoring visits or monitoring plans
  • Suspend or terminate individual protocols
  • Restrict researcher’s research activities

Request for Reconsideration

A PI may request a reconsideration of the IRB’s determination. Requests must be limited to claims that either (1) the process was faulty, resulting in considerable risk that the outcome was incorrect; or (2) that the findings and/or corrective actions imposed by the IRB were excessive or unjustified. The written request must be submitted within 14 days of receipt of the summary report and must specify the nature of any claimed procedural error or the perceived unfairness of actions taken. Reconsiderations will be conducted by an IRB Chair (Executive Chair, Chair, or Associate Chair), or Designee. The reconsideration process will result in one of three outcomes, either the summary report will stand and it will become final, the summary report will be modified and become final, or further investigation is necessary and will be initiated.

Required Reporting

When noncompliance is determined to be serious and/or continuing, the final report will be forwarded to federal regulators if required, and to applicable Institutional Officials, the Departmental Chair, the Dean, University Compliance Services, and sponsors, if applicable.

Guiding Principles for NonCompliance Review

Protection of Human Subjects: The University of Vermont and UVM Medical Center are responsible for safeguarding the rights and welfare of human subjects involved in any research activity.

Fairness: The IRB strives to maintain a review that is impartial and honest, free from self-interest, prejudice or favoritism.

Communication: The committee will communicate with the PI during the review process at points determined to be appropriate by the IRB designee.

Confidentiality: All IRB discussions and documents regarding a situation of noncompliance are considered sensitive and will be handled in a confidential manner and in accordance with state and federal regulations. The IRB cannot, however, guarantee complete anonymity to informants or witnesses. Confidentiality will be maintained to the extent possible to protect privacy and prevent retaliation, while still allowing for a full and fair review. Information may be shared, as described above under Required Reporting.

Conflict of Interest: Any IRB member who feels that they have a conflicting interest must recuse themselves from reviewing the issue of noncompliance. IRB members who are also listed as key personnel on the protocol(s) will not participate in the review but may be asked for information.

Procedures: In addition to what has been stated within this policy, the Committee will follow all applicable procedures that are outlined within the Committee Operating Procedures document.

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28. Electronic Signatures Policy

Requirement for Compliance

FDA issued 21 CRF part 11 regulations that provide criteria for FDA acceptance of, under certain circumstances, electronic records, electronic signatures, and handwritten signatures executed to electronic records as equivalent to paper records and handwritten signatures executed on paper. These regulations, which apply to all FDA program areas, were intended to permit the widest possible use of electronic technology, compatible with FDA's responsibility to protect the public health.

Part 11 requires assurances in three basic areas: Record Archiving (audit trail), Electronic Signatures, and Security Controls.

Achieving Compliance

InfoEd in combination with institutional controls, meets the regulatory requirements in each of the areas of Record Archiving (audit trail), Electronic Signatures, and Security Controls.

The system and information tracked in it includes, but is not limited to, versioning of submissions, time and date stamps on routing, time and date stamps on status history, record access history and login history.

Institutional policy regarding authentication, configuration of security and workflow controls, and limits on access to the database, this supports the record archiving (audit trail) and security controls necessary for compliance.

The electronic signature procedure, which secures the user authentication (proof of claimed identity) at the same time the signature is generated, provides the same assurance as an original signature on a paper document, and signifies acceptance and adherence to the Committees’ certification and investigator agreement.

Definitions

Principal Investigator (PI) – The researcher who is responsible for the conduct of a research study at an institutional site.

InfoEd – An online protocol submission and review system utilized by the Research Protections Office, also referred to as “the system.”

InfoEd Delegate – The PI has the option to delegate a specific person or persons to create submissions and in some instances submit the protocol package. The delegation feature in the InfoEd system allows the assigned delegate(s) to view everything that the PI can view within the InfoEd system, including all protocol and grant information for that PI.

InfoEd electronic signature – InfoEd electronic signatures are based on use of a UVM NetID and the associated network account password (authentication). Authentication ensures no two individuals have the same combination of identification. Passwords must be regularly updated in accordance with University information security policies.

Current Procedure for Signatures on Paper Applications Uploaded to the System

The PI signs and dates the paper application, and the signed application is submitted electronically through the InfoEd system. The PI must submit the application in InfoEd or alternatively, the PI may request to the RPO office that their primary contact person be delegated the ability to submit the application on his/her behalf. Consistent with PI requirements, delegates are required to sign into the system with a UVM NeID and password.

Future Procedure for Electronic Signatures within the System

In the future, the electronic submission of documents will be replaced with electronic forms directly in the system. At that point there will no longer be a physical PI signature on the application. To meet the regulatory requirement for a valid electronic signature, all protocol submissions utilizing InfoEd’s electronic form sets must be submitted by the PI and may no longer be submitted by a primary contacted who has been delegated that authority.

The PI may request to the RPO office that their primary contact person be delegated the ability to assist in the preparation of the protocol submission. Once a delegate has completed his/her work on the submission, the PI must then enter their NetID and password into InfoEd to review the materials, agree to the Investigator Certification language, and click the submit button.

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29. Regulatory Definitions

  • Accrual. The number of subjects who have completed or are actively in the process of completing a study. This does not include screen failures. It does include withdrawals. Example: You enroll 100 to accrue 25.
  • Administrative hold. A voluntary action initiated by the principle investigator whenever specific research activities, including subject enrollment, are placed temporarily on hold.
  • Adverse event. An untoward or undesirable experience associated with the use of a medical product, such as a drug, device or biologic, in a patient or research subject.
  • Advocate. An individual who has the background and experience to act in, and agrees to act in, the best interest of the child for the duration of the child's participation in the clinical investigation.
  • Agent. For purposes of this document, an institution's employees or agents refers to individuals who: (1) act on behalf of the institution; (2) exercise institutional authority or responsibility; or (3) perform institutionally designated activities. "Employees and agents" can include staff, students, contractors and volunteers, among others, regardless of whether the individual is receiving compensation. A student's affiliation with an academic institution makes him or her an agent of that institution; and thus the academic institution is engaged in the research regardless of where the research takes place.
  • Allegation of noncompliance. An unproven assertion of noncompliance.
  • Alternate member. Alternate Institutional Review Board (IRB) committee members may be designated, as needed, for regular voting members. The appointment of alternate members should be based on expertise similar to that of the regular voting member. An alternate member may vote only when the regular voting member is absent.
  • Anonymous data. Information that was previously recorded or collected without any of the 18 identifiers as defined by HIPAA, and no code is assigned that would allow data to be traced to an individual.
  • Assent. A child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.
  • Assured institution. An institution with a federalwide assurance (FWA) that has filed with the federal Office for Human Research Protections. Employees and agents of the institution holding an approved FWA are covered whenever they are involved in the conduct of the research covered by the FWA. Employees and agents are individuals performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility.
  • Belmont Report. Report by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research identifying the basic ethical principles underlying the conduct of research involving human subjects, that is, respect for persons, beneficence and justice.
  • Beneficence. Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. Such treatment falls under the principle of beneficence. Two general rules have been formulated as expressions of beneficent actions (Belmont Report, 1978):
    1. Do no harm, and
    2. Maximize possible benefits and minimize possible harms.
  • Benign behavioral interventions. Interventions brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. Examples:
  • Requesting subjects play an online game
  • Solve puzzles under various noise conditions
  • Decide how to allocate a nominal amount of received cash between themselves and someone else.
  • Biologic product. A biological product (biologic) is a medical product. Many biologics are made from a variety of natural sources, such as humans, animals or microorganisms. Like drugs, some biologics are intended to treat diseases and medical conditions. Other biologics are used to prevent or diagnose diseases. Examples of biological products include:
    1. Vaccines
    2. Blood and blood products for transfusion and or manufacturing into other products
    3. Allergenic extracts, which are used for both diagnosis and treatment, such as allergy shots
    4. Human cells and tissues used for transplantation, such as tendons, ligaments and bone
    5. Gene therapies
    6. Cellular therapies
    7. Tests to screen potential blood donors for infectious agents, such as HIV
    8. In general, the term "drugs" includes therapeutic biological products
  • Broad Consent. Broad consent is an option for storage, maintenance, and secondary research use of identifiable private information and identifiable biospecimens. Not in use at UVM.
  • Certification. Official notification by the institution to the supporting Federal department or agency component, that a research project or activity involving human subjects has been reviewed and approved by an IRB in accordance with an approved assurance.
  • Children. People who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.
  • Clinical investigation. The Food and Drug Administration (FDA) has defined clinical investigation to be synonymous with research. The FDA defines clinical investigation as any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA or the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit.
  • Clinical Trial. Clinical trial means a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
  • Coded information and data. Identifying information that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol or combination thereof and a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.
  • Conflict of interest. Any interest that could reasonably be expected to affect the objectivity of an IRB member or consultant in relation to an application or other matter under IRB review. An IRB member or consultant has a conflict of interest if the individual:
    1. Is or will be an investigator or member of the research team (that is, listed on the IRB application)
    2. Has an immediate family member (that is, spouse, dependent children) or personal relationship with an individual who is one of the investigators
    3. Has a financial or managerial interest in a sponsoring entity or product being evaluated or provided by a commercial entity in the research, as defined by UVM/UVMMC policies
    4. Has received or will receive compensation with value (as defined by UVM/UVMMC policies) that may be affected by the outcome of the research project
    5. Has a proprietary interest in the research, such as a nonprovisional patent application, patent, trademark, copyright or licensing agreement as defined by UVM/UVMMC policies
    6. Has a nonfinancial interest (personal circumstance, ethical belief, or other factor) that may be conflicting, for example, the IRB member has an interest that he or she believes conflicts with his or her ability to review a project objectively
    7. Has responsibility for institutional business development, such as raising funds or garnering support for research or as an officer within the Department of Development
  • Consent capacity. An individual's ability to understand and process information relevant to making an informed, voluntary decision to participate in research. Several kinds of information are crucial to such decisions, including an understanding of the purpose of the study, its experimental nature, risks and anticipated benefits, the right to withdraw, alternatives to participation, confidentiality protections, and the safeguards used to minimize risks. A wide variety of diseases, disorders, conditions, situations and injuries can affect a person's ability to understand such information, to weigh the advantages and disadvantages of participation in research, and to reach an informed decision regarding study participation.
  • Consent document. A structured, written description in understandable terms of relevant research project information. The consent document is not consent itself; it is the record of what has been communicated to a potential participant. It is the document that ensures all regulatory elements are present and communicated to a potential participant. When signed by the potential participant, the consent document is a record of the receipt of research-related information by the participant. It also serves as reference material for the participant as the research project progresses. It is not a contract and is not legally binding, and the participant may choose to withdraw consent at any time.
  • Consultant. A scientist or nonscientist from within or external to UVM/UVMMC who has special expertise to act — at the request of the IRB — as an ad hoc reviewer of a research project application. These individuals have access to all documents relevant to the specific project under review, may participate in the deliberations and make recommendations on the project, but may not vote and are not counted toward quorum.
  • Continuing noncompliance. A pattern or multiple instances of noncompliance that, if unaddressed, could: a) compromise the rights and welfare of subjects; b) impact the integrity and validity of the study data; and/or c) compromise the integrity and effectiveness of the UVM Research Protection Program.
  • Continuing review. Periodic review of research activities at intervals appropriate to the degree of risk, but not less than once per year. The criteria for approval are defined by federal regulations. Unless the IRB determines otherwise, continuing review will no longer be required for: projects under expedited categories, projects requiring limited IRB review, or projects that have progressed to data analysis (including analysis of identifiable private information or identifiable biospecimens).
  • Cooperative research project. Research projects that involve more than one institution as defined by federal regulations.
  • Coordinating center. An institution, department or center that agrees to be responsible for the conduct and administrative or coordinating functions of a multicenter research project.
  • Co-principal investigator (co-PI). UVM/UVMMC investigator who plays a key role in scientific development and conduct of the study. The co-PI collaborates with the principal investigator who has overall responsibility for study conduct. Conditions of eligibility for the role of co-PI are the same as for a PI. Students, residents, fellows and research temporary professional personnel (appointees) are not eligible to be a PI or co-PI on IRB or IACUC-approved research.
  • Covered entity. HIPAA regulations apply to health plans, health care clearinghouses and health care providers who transmit health information. Any individual creating or accessing protected health information (PHI) for the delivery of health care at UVM/UVMMC is within the covered entity.
  • Custom device. Custom device means a device that:
    1. Necessarily deviates from devices generally available or from an applicable performance standard or premarket approval requirement in order to comply with the order of an individual physician or dentist;
    2. Is not generally available to, or generally used by, other physicians or dentists;
    3. Is not generally available in finished form for purchase or for dispensing upon prescription;
    4. Is not offered for commercial distribution through labeling or advertising; and
    5. Is intended for use by an individual patient named in the order of a physician or dentist, and is to be made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice (such as a particular operating tool).
  • Data safety monitoring board (DSMB). A data safety monitoring board is an independent committee set up specifically to monitor data throughout the duration of a study to determine if continuation of the study is appropriate scientifically and ethically. Factors that suggest a DSMB is needed:
    1. A large study population and
    2. Multiple study sites. It is more difficult to recognize a pattern of increased or unusual problems or events when investigators treat small fractions of the population separately;
    3. Highly toxic therapies or dangerous procedures;
    4. High expected rates of morbidity or mortality in the study population;
    5. High chance of early termination of the study. DSMB membership is usually comprised of experts in the fields of medicine and science that are applicable to the study — statistical experts, lay representatives and others who can offer an unbiased assessment of the study progress.
  • Data safety monitoring plan (DSMP). A DSMP is a quality-assurance plan for a research study. A data and safety monitoring plan (DSMP) is meant to ensure that each clinical investigation has a system for appropriate oversight and monitoring of the conduct of the clinical investigation. The purpose of a DSMP is to ensure the safety of the participants, the validity of the data and the integrity of the study, and the appropriate termination of studies for which significant benefits or risk has been uncovered or when it appears that the investigation cannot be concluded successfully. A DSMP is commensurate with the risks involved with the research study. The DSMP may include a data and safety monitoring board (DSMB).
  • Data use agreement. An agreement into which UVM/UVMMC and the investigator enter with the intended recipient of a limited data set that establishes the ways in which the information in the limited data set may be used and how it will be protected.
  • Dead fetus. A fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles nor pulsation of the umbilical cord.
  • De-identified health information. Health information that has been stripped of all 18 identifiers as defined by HIPAA so that the information cannot be traced back to an individual. De-identified data also pertains to health information that has been assigned and retains a code or other means of identification provided that:
    1. The code is not derived from or related to the information about the individual;
    2. The code could not be translated to identify the individual; and
    3. The covered entity does not use or disclose the code for other purposes or disclose the mechanism for re-identification.
The 18 identifiers:

1. Names

2. All geographic subdivisions smaller than a state*

3. Telephone numbers

4. Fax numbers

5. Electronic mail addresses

6. Social Security numbers

7. Medical record numbers

8. Health plan beneficiary numbers

9. Account numbers

10. Certificate/license numbers

11. Vehicle identifiers and serial numbers, including license plate numbers

12. Device identifiers and serial numbers

13. Web Universal Resource Locators (URLs)

14. Internet Protocol (IP) address numbers

15. Biometric identifiers, including finger and voice prints

16. Full face photographic images and any comparable images

17. All elements of dates (except year)**

18. Any other unique identifying number, characteristic or code

*including street address, city, county, precinct, zip code, and their equivalent geocodes, except for the initial three digits of a zip code, if according to the current publicly available data from the Bureau of the Census: (1) The geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and (2) The initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000.

**for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older.

  • Delivery. Complete separation of the fetus from the woman by expulsion or extraction or any other means.
  • Disclosure of PHI. The release, transfer, or provision of access to, or divulging in any manner of, information outside the covered entity.
  • Documentation. The act or an instance of furnishing or authenticating with documents.
  • Emergency research. Planned research involving human subjects who have a life-threatening medical condition that necessitates urgent intervention (for which available treatments are unproven or unsatisfactory), and who, because of their condition (such as traumatic brain injury) cannot provide informed consent.
  • Emergency treatment IDE. A mechanism through the FDA for providing eligible participants with investigational devices for the treatment of an immediate serious or life-threatening illness for which there are no satisfactory alternatives.
  • Emergency treatment IND. A mechanism through the FDA for providing eligible participants with investigational drugs, agents or biologics for the treatment of an immediate serious or life-threatening illness for which there are no satisfactory alternatives.
  • Emergency use. Use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval [21 CFR 56.102(d)].
    1. Life-threatening includes both life-threatening and severely debilitating diseases or conditions where likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the endpoint of clinical trial analysis is survival.
    2. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened IRB meeting is feasible.
    3. Severely debilitating: Diseases or conditions that cause major irreversible morbidity, such as blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis, or stroke.
  • Engagement of institutions in human subject research. An organization is considered engaged in human research when its employees or agents, for the purposes of the nonexempt research project, obtain:
    1. Data about the subjects of the research through intervention or interaction with them;
    2. Identifiable private information about the subjects of the research;
    3. The informed consent of human subjects for the research; or
    4. When the institution receives a direct federal award to conduct human subject research, even when all activities involving human subjects are carried out by a subcontractor (that is, employees or agents of another institution).
  • Enrollment. Occurs when an eligible, informed, potential participant undergoes the initial informed consent process and voluntarily agrees to participate in a research project. Example: You enroll 100 to accrue 25. See also Accrual.
  • Exempt human subjects research. Studies determined by the IRB to meet the exempt criteria as defined by the federal regulations. Exempt studies do not require periodic review by the IRB unless a change in the project is planned.
  • Expedited review. A review of research involving human subjects by the IRB chair or by one or more experienced reviewers designated by the chair from among members of the IRB in accordance with the requirements set forth in 45 CFR 46.110.
  • Experimental subject (as defined by Department of Defense, or DOD). Research involving a human being as an experimental subject is an activity, for research purposes, where there is an intervention or interaction with a human being for the primary purpose of obtaining data regarding the effect of the intervention or interaction [32 CFR.210.102 (f) reference (c)]. Examples include, but are not limited to, a physical procedure, a drug, a manipulation of the subject or subject's environment, and the withholding of an intervention that would have been undertaken if not for the research purpose.
  • Expired study. When continuing review of the research does not occur prior to the end of the approval period specified by the IRB, IRB approval expires automatically. The study expires on the date specified on the approval letter and the consent document. No activities can occur after the expiration date.
  • External Unanticipated Problem.  A problem or event involving research subjects enrolled by other institutions in multicenter research projects that fall under the purview of an external IRB, that is, not the UVM IRB.
  • Federalwide assurance (FWA). A formal, written, binding attestation in which an institution ensures to the Department of Health and Human Services (HHS) that it will comply with applicable regulations governing research with human subjects.
  • Fetus. The product of conception from implantation until delivery.
  • Final report. A report the principal investigator may elect to submit to the IRB to serve as a final record of any pertinent activity since the last continuing review report and to record research project completion.
  • Fluctuating capacity. Capacity to consent may alter as a function of the natural course of an illness, response to treatment, effects of medication, general physical health, and other factors. Therefore, a participant's ability to provide ongoing informed consent must be re-evaluated periodically throughout the course of his or her participation in a study.
  • Food and Drug Administration (FDA). The regulatory authority in the United States that oversees the pharmaceutical and medical device industries. The FDA is responsible for ensuring that the drugs and medical devices marketed in the U.S. are safe and have a greater benefit than risk when used according to manufacturer's directions.
  • Full committee review. Studies reviewed by the full, convened IRB committee with a recorded vote and corresponding minutes to document the discussion.
  • Greater than minimal risk. The research involves more than minimal risk to subjects.
  • Guardian. An individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care when general medical care includes participation in research.
  • HIPAA authorization. A customized document or form that gives permission to use specified protected health information (PHI) for a specific purpose, or to disclose PHI to a third party specified by the investigator other than for treatment, payment or health care operations.
  • Honest Broker. An honest broker is an individual who has access to the desired data by virtue of his or her responsibilities and who is not involved as a listed researcher on the respective research study.
  • The honest broker accesses the desired medical record information and provides the researcher with de-identified data or a limited data set.
  • If the honest broker is providing the researcher with a limited data set, the broker must present an internal data use agreement to the researcher prior to receiving the data set.
  • The honest broker can assign a code to the data, provided that the researcher does not have access to the information linking the code to the identities of the research subjects. Using the code, the researcher can request, through the honest broker, additional medical information corresponding to a given research subject.
  • If the honest broker provides coded data to the research but not the method to de-code the data, then the information provided will be considered de-identified or a limited data set depending upon the data elements included in the data set.
  • Human biospecimens. A quantity of tissue, blood, urine or other human-derived material. A single biopsy may generate several biospecimens, including multiple paraffin blocks or frozen biospecimens. The molecular makeup of such specimens reflects the physiologic or pathologic condition of the person from whom they derive; therefore, they provide sensitive and specific insight into the biologic state of the donor. A biospecimen can include subcellular structures (such as DNA), cells, tissue (such as bone, muscle, connective tissue and skin), organs (such as liver, bladder, heart and kidney), blood, gametes, embryos, fetal tissue, and waste (such as urine and stool). Portions or aliquots of a biospecimen are referred to as samples. (Derived from National Cancer Institute Best Practices for Biospecimen Research.)
  • Humanitarian use device exemption (HDE). An FDA approval for a physician to use a humanitarian use device (HUD) in clinical treatment or as the subject of a clinical investigation.
  • Humanitarian use device (HUD). A device that is intended to benefit patients by treating or diagnosing a disease or condition that affects fewer than 4,000 individuals in the U.S. per year.
  • Human specimen research repository. A collection of human specimens and associated data for research purposes, the physical structure where the collection is stored, and all relevant processes and procedures.
  • Human subject as defined by Department of Defense:
    1. Research involving a human being as an experimental subject. An activity, for research purposes, where there is an intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction.
    2. Research involving human subjects. An activity that includes both a systematic investigation designed to develop or contribute to generalizable knowledge and involve a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or identifiable private information.
  • Human subject as defined by FDA. An individual who is or becomes a subject in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient. A human subject includes an individual on whose specimen a medical device is used.
    1. Test article: Any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product or any other article subject to FDA regulation.
  • Human subject as defined by HHS. Human subject means a living individual about whom an investigator (whether professional or student) conducting research:
  • (i)Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; OR
  • (ii)Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.
  • Human subject identifier. Any word, number, symbol, or combination of words, numbers or symbols that can be used by a third party to uniquely identify an individual, such as name, Social Security number, address or patient registration number that is provided for use in a research protocol.
  • Identifiable private information. Is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information.
  • Identifiable biospecimen. A biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.
  • Impaired consent capacity. Impaired consent capacity may involve partial impairment, impairment that fluctuates over time or complete impairment. For example, consent capacity can be affected by a wide range of disorders and conditions, such as dementia, stroke, traumatic brain injury, developmental disorders, serious mental illness, intoxication and delirium.
  • Individually identifiable health information. Any information collected from an individual (including demographics) that is created or received by a health care provider, health plan, employer, and or health care clearinghouse that relates to the past, present or future physical or mental health or condition of an individual, or the provision of health care to an individual or the past, present or future payment for the provision of health care to an individual and identifies the individual and or to which there is reasonable basis to believe that the information can be used to identify the individual.
  • Informed consent. An ongoing process of communication between the participant and the study team. Informed consent is a continuing process by which a participant, after having been informed, voluntarily confirms his or her willingness to participate in a research project and can demonstrate understanding of all aspects of the research project that are relevant to the participant's decision to participate.
  • Institutional official. The institutional official (IO) who is the signatory on the federal wide assurance (FWA) filed with OHRP to ensure compliance with regulations governing protection of human subjects. OHRP requires the institutional official to be a high-level official who has the authority to represent the institution named in the FWA.
  • Institutional review board (IRB). A specifically constituted review body established or designated by an entity to protect the rights and welfare of human subjects recruited to participate in biomedical or behavioral or social science research.
  • Interaction. Includes communication or interpersonal contact between investigator and subject.
  • Intervention. Physical procedures by which information or biospecimens are gathered, such as venipuncture, and manipulations of the subject or the subject's environment that are performed for research purposes.
  • Investigational agent. A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes products with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, products used for an unapproved indication or products used to gain further information about an approved use.
  • Investigational device. Any health care product that does not achieve its primary intended purposes by chemical action or by being metabolized. A medical device that is the subject of a clinical study designed to evaluate the effectiveness and or safety of the device. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices.
  • Investigational device exemption (IDE). Application document submitted to the FDA proposing human clinical research to study an unapproved significant risk device, or a cleared or approved device for use other than its approved indication or intent. FDA grants permission so a device that otherwise would be required to comply with a performance standard or to have premarket approval can be shipped lawfully for the purpose of conducting investigations of that device. This FDA permission is evidenced by the assignment of an IDE number.
  • Investigational drugs or investigational biologics. New drugs or biologics that have not yet been approved by the FDA or approved drugs that have not yet been approved for a new use, and are in the process of being tested for safety and effectiveness.
  • IND (investigational new drug) application. Means by which permission may be obtained to 1) ship an investigational drug, biologic or agent across state lines and 2) use in humans prior to FDA review of clinical data that has determined a new drug, agent or biologic to be safe and effective for a specific use. Testing of an investigational product may proceed once a valid IND is in effect or an IND exemption has been granted.
  • IRB authorization agreement. A formal, written agreement in which the reviewing IRB agrees to serve as the IRB of record for a relying institution, including an academic institution. Agreements are generally used to cover a single research study, categories of research studies or research studies within a research program.
  • IRB of record. A reviewing IRB that assumes IRB responsibilities for another institution and is designated to do so through an approved federal wide assurance on file with the federal Office for Human Research Protections.
  • Label. The FDA-approved label is the official description of a drug or biologic product that includes indication (what the product is used for); who should take it; adverse events (side effects); instructions for uses in pregnancy, children and other populations; and safety information for the patient. Labels are often found inside product packaging.
  • Legally authorized representative (LAR). Legally authorized representative (LAR) means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research. If there is no applicable law addressing this issue, legally authorized representative means an individual recognized by institutional policy as acceptable for providing consent in the nonresearch context on behalf of the prospective subject to the subject’s participation in the procedure(s) involved in the research.
  • Legally effective informed consent. A potential participant has been provided enough information to make a decision; the potential participant has the capacity to make a decision; the potential participant understands the consequences of his or her decision; and the potential participant can communicate that decision.
  • Limited data set. A limited data set allows retention of specific elements of identifying private information: geographic subdivisions, town, city, state, ZIP code, dates, age. Limited data sets are not considered to be de-identified information.
  • Limited Review. Limited IRB review is a term that the 2018 Common Rule uses to describe an expedited review of an exempt level project.
  • Local research context. Knowledge of the institution and community environment in which human subjects research will be conducted.
  • Material transfer agreement (MTA). A contract that governs the transfer of tangible research materials between two organizations when the recipient intends to use the materials for his or her own research purposes.
  • Medical device. A medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory that is:
    1. Listed in the online FDA database.
    2. Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease, in man or other animals, or
    3. Intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes [21 U.S.C. 321(h)].
  • Minimal risk. The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
  • Minimal risk for prisoners. The probability and magnitude of physical or psychological harm that is normally encountered in the daily lives or in the routine medical, dental or psychological examination of healthy persons. The regulations further state that the IRB must find that the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers [45 CFR 46.305(a)(3)]. If Subpart C does not apply, the IRB may use an equivalent definition of minimal risk for prisoners. [45 CFR 46.303(d)]
  • Modification. Any change to an IRB-approved study protocol regardless of the level of review it receives initially.
  • Neonate. A newborn zero to 28 days old.
  • Nonaffiliated member. Any IRB member who is not currently affiliated with UVM/UVMMC and whose immediate family members are not affiliated with UVM/UVMMC. Examples of UVM/UVMMC affiliation include employment, participation as a student in a UVM academic program or receipt of post-employment benefits, such as health and wellness or a pension.
  • Noncompliance. An act or omission in the conduct or oversight of human subject research that represents a failure to follow: 1) federal, state or local regulations; 2) institutional policies relevant to human subject research; 3) the approved research plan; and/or 4) the determinations of the IRB.
  • Non-unanticipated problem involving risk to subjects or others. A reportable event that does not meet the UVM IRB's definition of an unanticipated event involving risk to subjects or others. See Unanticipated problem involving risk to subjects or others.
  • Nonviable neonate. A neonate after delivery that, although living, is not viable.
  • Notification. Process of notifying research subjects of changes in the research by letter or phone.
  • Not Research. The following activities are deemed not to be research:
    (1) Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected.
    (2) Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).
    (3) Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.
    (4) Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
  • Office for Human Research Protections (OHRP). The office under the Department of Health and Human Services responsible for implementing HHS regulations (45 CFR 46) governing biomedical and behavioral and or social science research involving human subjects.
  • Oral (verbal) consent. A spoken presentation of the elements of informed consent to the prospective subject or their legally authorized representative. The presentation may be based on information contained within an oral consent script or the written consent document. Oral consent is often associated with waiving the documentation of consent. Oral consent is usually recorded in the research project files.
  • Permission. The agreement of parents or guardians to the participation of their child or ward in research.
  • Pregnancy. Encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as a missed menses, until the results of a pregnancy test are negative or until delivery.
  • Preparatory to research. Any action taken in assessing the research question or hypothesis, such as accessing medical records, querying of databases for any type of individually identifiable health information, or any activity where PHI is accessed to prepare a research protocol.
  • Principal investigator (PI). Adheres to federal regulations, state and local laws, institutional policies, IRB policies and procedures regarding the safety and protection of human subjects, and good clinical practice (GCP) guidelines. The principal investigator ensures adherence by:
    1. Supervising the research process.
    2. Taking responsibility for ensuring that key study personnel are properly trained, qualified, and have appropriate facilities and resources to conduct the research.
    3. Ensuring adherence to the study protocol.
    4. Monitoring the informed consent process.
    5. Communicating regularly and effectively with the research staff.
    6. Taking responsibility for protecting the safety and welfare of research subjects.
  • Prisoner. Any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures that provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial or sentencing. If Subpart C does not apply, the IRB may use an equivalent definition of prisoners. [45 CFR 46.303(c)]
  • Prisoner of war. Any person captured, detained, held or otherwise under the control of Department of Defense personnel (military and civilian, or contractor employee) except DOD personnel held for law enforcement purposes (DOD directive 3216.2, section 4.42).
  • Privacy versus confidentiality. Privacy is about people and their choice to share personal information. It is a right in health care and research. Confidentiality is about data. It is the investigator's obligation to protect subjects' information.
  • Private information. Information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place. It includes information that has been provided for specific purposes by an individual, and the individual can reasonably expect will not be made public, such as a medical record. Private information must be individually identifiable in order to be considered information to constitute research involving human subjects. This may include identifiable private information obtained from a primary subject about a third party.
  • Protected health information. Individually identifiable health information transmitted by electronic media, maintained in electronic media or maintained in any other form.
  • Protocol violation. Problems that violate the terms of a study but do not meet the criteria for an unanticipated risk to subjects or others. See Unanticipated problem involving risk to subjects or others.
  • Public Health Authority. Agency or authority that is responsible for public health matters as part of its official mandate.
  • Reconsenting. Process of notifying research subjects of changes in the research, including documentation of the subject's continued informed consent through signature on a revised written consent form.
  • Recruitment. Recruitment, a component of the consent process, is the process of distributing or presenting information that describes the research project and eligibility criteria so that a prospective subject may consider enrollment.
  • Recruitment screening/waivers. Allows waiver of informed consent for subject recruitment or screening, under certain conditions.
  • Relying organization. An organization, including an academic institution, with whom UVM has either entered into an IRB Authorization Agreement or an agreement entered into as part of a cooperative research project.
  • Reportable event. A process (with an associated IRB form) used by an investigator to report any problem or event or other act or omission to the IRB that in their opinion is a an unanticipated problem involving risk to subjects or others. Repository. A repository compiles data, specimens, or both for future research purposes. The repository receives, processes, stores, and distributes data with or without specimens to researchers. The repository may or may not have an honest broker.
  • Research activities. Research activity includes all contact with the research subject (such as enrolling subjects, intervention or interaction), data collection and data analysis.
  • Research (as defined by DOD). An activity that includes both a systematic investigation designed to develop or contribute to generalizable knowledge and involves a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or identifiable private information, or activities covered by section 32 CFR 219.101 (including exempt research involving human subjects) and DOD Instruction 3216.02.
  • Research (as defined by FDA). Any experiment that involves a test article and one or more human subjects, and that meets any one of the following:
    1. Must meet the requirements for prior submission to the FDA under section 505(i) of the Federal Food, Drug, and Cosmetic Act, meaning any use of a drug other than the use of an approved drug in the course of medical practice
    2. Must meet the requirements for prior submission to the Food and Drug Administration under section 520(g) of the Federal Food, Drug, and Cosmetic Act, meaning any activity that evaluates the safety or effectiveness of a device
    3. Any activity the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit
  • Research (as defined by HHS). A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes. Some demonstration and service programs may include research activities. For the purposes of this part, the following activities are deemed not to be research:
    1. Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected.
    2. Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).
    3. Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.
    4. Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
  • Research involving a human being as an experimental subject (as defined by DOD). An activity, for research purposes, where there is an intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction. Research involving a human being as an experimental subject is a subset of research involving human subjects. This definition relates only to the application of section 980 of Title 10 USC; it does not affect the application of 32 CFR 219. This definition does not include activities that are not considered research involving human subjects, activities that meet the exemption criteria at section 32 CFR 219.101(b), and research involving the collection or study of existing data, documents, records, or specimens from living individuals. Section 980 of Title 10 USC imposes limitations on waiving informed consent when using DOD appropriated funds. Section 980 of Title 10 USC is applicable only to DOD funded research involving a human being as an experimental subject. Section 980 of Title 10 USC is not applicable to exempt research involving human subjects.
  • Research involving human subjects (as defined by DOD). An activity that includes both a systematic investigation designed to develop or contribute to generalizable knowledge and involves a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or identifiable private information, or activities covered by section 32 CFR 219.101 (including exempt research involving human subjects) and DOD Instruction 3216.02.
  • Screen failures. Subjects who consented to participate in research but who were disqualified during screening procedures.
  • Serious noncompliance. Any noncompliance that results in or has the potential to: a) substantially compromise the rights and welfare of subjects; b) substantially impact the integrity and validity of the study data; and c) compromise the integrity and effectiveness of the UVM Human Research Protection Program.
  • Short-form consent document. A written consent document stating that the elements of consent have been presented orally. A witness to the oral presentation is required.
  • Significant risk (SR) device study. A study of a device that presents a potential for serious risk to the health, safety or welfare of a participant and:
    1. Is intended as an implant;
    2. Is used in supporting or sustaining human life, or otherwise prevents impairment of human health;
    3. Is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health; or
    4. Otherwise presents a potential for serious risk to the health, safety or welfare of a participant.
  • Single IRB. Single IRBs have overall regulatory review responsibilities (by agreement) for multiple-site research protocols. U.S. Institutions engaged in cooperative (multi-site) research must rely upon approval by a single IRB by January 2020.
  • Sponsor-investigator. An individual who both initiates and conducts an investigation, and under whose immediate direction:
    1. The investigational drug is administered or dispensed, and or
    2. The investigational device is administered, dispensed or used. The term does not include any person other than an individual.
  • Study expiration. If IRB approval of a specific study expires before continuing review and approval occur, investigators must stop all research activities involving human subjects related to that study except where they judge that it is in the best interests of already enrolled subjects to continue to participate. When investigators make this judgment, they must promptly notify the IRB. When the IRB reviews the investigator's decision, it may decide whether it is in the best interests of already-enrolled subjects to continue to participate in the research by considering the best interests of subjects either one at a time or as a group. If an IRB determines that it is not in the best interests of already-enrolled subjects to continue to participate, investigators must stop all human subjects research activities, including intervening or interacting with subjects, or obtaining or analyzing identifiable private information about human subjects. Investigators may resume the human subjects research activity once continuing review and approval by the IRB has occurred.
  • Surrogate consent. Consent obtained from the participant's legally authorized representative (LAR).
  • Suspension for cause. An action initiated by the IRB to stop temporarily some or all research procedures pending future action by the IRB or by the investigator or his or her personnel. Examples of a suspension for cause might include:
    1. Inappropriate involvement of human subjects in research
    2. Violation of the rights or welfare of human subjects or others
    3. Serious or continuing noncompliance with federal regulations or IRB policies
    4. New information regarding increased risk to human subjects or others
  • Termination for cause. An action initiated by the IRB to stop permanently some or all research procedures.
  • Test article. Any investigational drug, biologic product, such as blood or a vaccine, or medical device for human use.
  • Therapeutic misconception. The term "therapeutic misconception" is used to describe the assumption by research participants that decisions about their care are being made solely with their benefit in mind. Therapeutic misconception can be defined as the situation where a participant or a LAR either overestimates the direct therapeutic benefits that may be gained by participation in the research and/or underestimates the risks, thereby compromising his or her ability to provide and/or maintain a voluntary and knowing informed consent. Investigators must be especially careful to make participants and their families or caretakers aware of the differences between individualized treatment versus research and the separate and distinct roles of the clinician and the research investigator.
  • Treatment investigational device exemption (IDE). A mechanism through the FDA for providing eligible participants with investigational devices for the treatment of a serious or life-threatening illness for which there are no satisfactory alternatives.
  • Treatment investigational new drug (IND). A mechanism through the FDA for providing eligible participants with investigational drugs for the treatment of a serious or life-threatening illness for which there are no satisfactory alternatives.
  • Unanticipated problem involving risk to subjects or others. Any unanticipated problem or adverse event that meets these three criteria:
    1. Serious. Serious problems or events that result in significant harm (which may be physical, psychological, financial, social, economic or legal) or increased risk for the subject or others (including individuals who are not research subjects). These include:
      1. Death;
      2. Life-threatening adverse experience;
      3. Hospitalization, whether inpatient, new or prolonged;
      4. Disability and or incapacity, whether persistent or significant;
      5. Birth defect or anomaly;
      6. Breach of confidentiality; and
      7. Other problems, events or new information (such as publications, DSMB reports, interim findings, product-labeling change) that in the opinion of the local investigator may adversely affect the rights, safety or welfare of the subjects or others, or substantially compromise the research data.
    2. Unanticipated. Unexpected problems or events are those that are not already described as potential risks in the protocol consent document, not listed in the investigator's brochure or not part of an underlying disease. A problem or event is unanticipated when it was unforeseeable at the time of its occurrence. A problem or event is unanticipated when it occurs at an increased frequency or at an increased severity than expected.
    3. Related. A problem or event is related if it is possibly related to the research procedures.
  • Viable. As it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.
  • Vulnerable populations in research. Vulnerable populations are individuals that are vulnerable to coercion or undue influence, such as children, prisoners or individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.
  • Ward. A child who is placed in the legal custody of the state or other agency, institution or entity, consistent with applicable federal, state or local law.
  • Withdrawals. Subjects who signed the consent form, but later withdrew from the study, either before or after receiving a study drug, device or intervention. This does not include screen failures.
  • Written or in Writing. Writing on a tangible medium (e.g., paper) or in an electronic format

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30. Statement of Compliance for the Committees on Human Research

statementofcompliance