The University of Vermont

Committees on Human Research

Serving The University of Vermont and Fletcher Allen Health Care

http://www.uvm.edu/irb/

 

 

November 18, 2011

 

 

Research Protections Office

 213 Waterman Bldg, 85 South Prospect St, Burlington, VT 05405, (802) 656-5040

INTRODUCTION 

 

The University of Vermont and Fletcher Allen Health Care have made a firm commitment to the protection of human research subjects.  The US Department of Health and Human Service regulations require each institution that conducts research involving human subjects to describe, in detail, the procedures it will use to protect the rights and welfare of the human subjects. Each institution prepares a document that describes these procedures. The document is called a “Federalwide Assurance” (FWA). 

 

UVM and FAHC each have a FWA which have identical written statements regarding our program of protections for human subjects in research. This includes our adherence to the ethical standards as well as our policies and procedures for the conduct of research involving human subjects.  These guidelines cover all internal and external funded research, as well as unfunded projects and are applicable to faculty, fellow, resident, and student-initiated projects.

 

Research with human subjects is considered any systematic investigation in which an investigator (student or professional) obtains data through intervention or interaction with an individual or identifiable private information.  This not only applies to physical interventions but to such activities as mail or telephone surveys, questionnaires or tests, interviews and observational research.  Review of records, especially those containing information individuals expect will not be made public (a medical or school record, for example) is also considered to be research.

 

As indicated in the Manual, different review procedures may be applied to research projects depending on the degree of risk presented to the subject and the nature of the procedures.  In addition to the medical sciences, these guidelines cover what may be considered behavioral, social science, and educational research, however benign, and must, at the very least, be submitted to the administrative office of the Committees on Human Research. 

 

Throughout this manual, all references to Committees on Human Research is interchangeable with the term Institutional Review Board (IRB).

 

The need for faculty attention to the conduct of human research projects by fellows, residents, and students is essential.  These projects are covered by University review requirements.  Some departments that have students conducting research with human subjects appoint a department representative to advise students on the conduct of such research projects and to act as a liaison between the student/department and the Committee office.  If there are any questions about students conducting research, they may be directed either to the department representative or the Committee office. 

 

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 Vermont Cancer Center (VCC) and the General Clinical Research Center (GCRC) are entities across UVM and FAHC 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 your research is supported by one of these units 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 protocol status, adverse events and monitoring information.  This sharing avoids duplication of efforts and also affords a higher level of protection for the subjects.

 

 

RESEARCH MANUAL FOR HUMAN SUBJECTS RESEARCH: 

 [Click here for a printer friendly PDF version.]

 

INTRODUCTION.. 2 1. COMMITTEE’S MISSION.. 6 2. COMMITTEE’S RESPONSIBILITIES/AUTHORITY.. 6 3. CONTACTS. 7 4. DETERMINATION IF PROJECT IS CONSIDERED RESEARCH OR INVOLVES HUMAN SUBJECTS. 9 A.  Before developing a proposal for research activity, you need to answer two critical questions about it:. 9 B.  Grant Proposals Lacking Definite Plans for Involvement of Human Subjects. 11 5. TRAINING REQUIREMENTS. 11 6. NON-FACULTY RESEARCHERS WHO CONDUCT HUMAN SUBJECT RESEARCH.. 13 6.A. Use of Human Subjects by UVM Students. 14 Research Practica or Class Projects. 14 Responsibility of Course Instructors When Class Projects are Exempt 15 Individual Research Projects, Directed or Independent that are Not Exempt 15 Responsibility of Course Instructors/Faculty Sponsors When Class Projects are Not Exempt 16 7. TYPES OF COMMITTEE REVIEWS. 16 7.A. “Full” Committee Review... 16 7.B. “Expedited” Review... 16 7.C. “Exempt” Research Review... 18 7.D.  “Research Not Involving Human Subjects” Review and Determination.. 20 8. Submission Materials for Initial Review... 20 8.A.  Protocol.. 20 8.A.1.   Elements. 20 8.A.2.  Common Protocol Cover Form or Research Involving Human Subjects Determination and Exemption. 25 8.A.3.  Blood Drawing Protocols. 25 8.A.4.  Biological Specimens/Data Repository Protocols. 27 8.B.  Informed Consent/HIPAA Authorization.. 30 8.B.1.  Consent Requirements/Elements. 30 8.B.2.  Consent Form/HIPAA Authorization Formats. 35 8.B.3.  Requirements for Preparing Consent Forms and HIPAA Authorizations in Foreign Language. 35 8.B.4.  Authorization Cover Form.. 36 8.B.5.  Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation of Informed Consent 36 8.B.6.  Waiver of Authorization. 38 8.B.7.  Request for Waiver of Informed Consent /Authorization/Documentation Form.. 38 8.B.8.  Request for a Partial Waiver of Authorization for Recruitment Purposes. 39 8.B.9. Request for Partial Waiver of Authorization for Recruitment Purposes Form.. 39 8.B.10.  “Legally Authorized Representatives” for Provision of Consent for Research in Emergency Settings. 39 8.B.11.  Guidelines for Non-Emergent Research Involving Individuals with Questionable Capacity to Consent 41 8.B.12.  Documentation:. 45 8.C.  Review of Grants/Contracts/Review Fees. 45 8.C.1.  New Competing or Competing Renewal Grant Applications. 45 8.C.2.   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 45 8.C.3.  Competing Resubmissions or Supplements. 46 8.C.4.  Just-in-Time Provision for IRB Submissions. 46 8.C.5.  Grant Proposals Lacking Definite Plans for Involvement of Human Subjects. 46 8.C.6.  Contracts. 47 8.C.7.  Review Fees. 47 8.C.8.  Changes to the Scope of a NIH Awarded Project 47 9. Submission of Materials After Initial Approval is Obtained.. 47 9.A. Continuing Review... 48 9.A.1.  Requirements. 48 9.A.2.  When to Report 49 9.A.3.  Request for Continuing Review Form.. 50 9.A.4.  Documentation:. 51 9.B.  Adverse Event and Unanticipated Problems Reporting.. 51 9.B.1.  Policies. 51 9.B.2.  Determining When to Report Local Unanticipated Problems:. 53 9.B.3.   The Local Report for Serious & Non-Serious Adverse Events Form.. 56 9.B.5.   Amendments to Protocol Submitted Due to New Safety Information. 56 9.B.6.  Documentation. 56 9.C.  Request for Modification/Amendment to Previously Approved Protocol.. 56 9.C.1.   Requirements:. 56 9.C.2    When to Request 58 9.C.3.   The Request for Modification / Amendment to Approved Protocol Form.. 58 9.C.4.   Documentation:. 58 9.D.  Notice of Protocol Closure or Request to Reopen a Closed Protocol.. 58 10. Investigator Responsibilities. 59 10.A.  Expectations of an Investigator.. 59 10.B.  Requirements of the Principal Investigator.. 59 10.B.1.  Ensure Proper Training of the Research Team.. 60 10.B.2.  Ensure Protocol Adherence. 60 10.B.3.  Create a Process of Informed Consent and HIPAA Authorization. 60 10.B.4.  Provide Reports on the Progress of the Study. 61 10.B.5  Coverage for PI or Faculty Sponsor. 62 10.B.6  Investigator’s Responsibilities when Leaving the University. 63 10.C.  Guidance for the Investigator.. 63 10.C.1.  Communication with the IRB.. 63 10.C.2.  Written Communication of IRB Decisions. 63 10.C.3.  Retention of Research Records. 64 10.C.4.  Accessibility of Records. 65 10.C.5.  Human Subject Recruitment/Retention Guidance. 65 10.C.6.  Investigator Financial Interest 68 11. Additional Protections For Special Populations. 70 11.A. Guidelines. 70 11.B. Pregnant Women, Fetuses, and Neonates. 71 11.C. Prisoners. 73 11.D. Children.. 74 12. Investigational Drugs and Devices. 77 12.A.  Research Involving Investigational Drugs. 77 12.A1.  Definition of an Investigational Drug from the FDA Regulations:. 77 12.A.2.  Use of Approved Drugs for Off-Label Indications:. 77 12.A.3.  Expanded Access of Investigational Drugs:. 77 12.B.  Research Involving Medical Devices. 80 12.B.1.  Definition of an Investigational Device. 80 12.B.2.  IRB Review of Investigational Device Protocols. 81 12.C.  Humanitarian Use Devices. 81 13. Multi-Institutional Research Studies. 83 13.A.  UVM/FAHC Researcher Collaborating with Another Institution.. 83 Multi-Institutional Research Studies FLOWCHART.. 84 13.B.  UVM/FAHC Researcher as the Lead PI in a Multi-Institutional Study.. 85   Attachments A: Emergency Use of an Investigational Drug, Biologic, or Device                     Certification of Compliance Form.. 88 B: POLICY – Subject Compensation for Participation in Research. 89 C: POLICY – Enrollment Incentives. 90 D: POLICY – Fees for Committee on Human Research Review of Sponsored Trials. 91 E: Committee Policies, Procedures and Guidance Documents. 92 F: Statement of Compliance for the Committees on Human Research. 93 G: Committee Forms. 94 H: POLICY – Human Subject Research Monitoring Program.. 95 I:  Guidance on Research Involving Coded Private Information or Biological Specimens. 96 J:  CHART: Research Involving Coded Private Information or Biological Specimens. 100 K:  Standards and Language for Studies Involving MRI 101

1. COMMITTEE’S MISSION

 

The University of Vermont and Fletcher Allen Health Care 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 Fletcher Allen Health Care 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 Sciences (CHRBS).  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. 

 

2. COMMITTEE’S RESPONSIBILITIES/AUTHORITY

 

The Committees on Human Research are charged with certain responsibilities and authority according to federal regulations and institutional policy. 

 

A. Review and have authority to approve, require modifications in, or disapprove research activities.

 

B. Require that information given to subjects as part of informed consent is in accordance with all requirements and 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 add to the protection of the rights and welfare of subjects.

 

C. Require documentation of informed consent or waive documentation in accordance with the regulations.

 

D. Require that waivers or alterations of consent comply with the requirements outlined in the federal regulations.

 

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.

 

F. Investigate and report to the appropriate institutional officials, OHRP, and, when applicable FDA and/or funding agency, any serious or continuing noncompliance with the federal regulations and requirements and determinations of the IRB.

 

G. Suspend or terminate approval of research that is not being conducted in accordance with the federal regulations and the IRB's requirements or 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 and OHRP.

 

H. Provide training for all individuals involved in the conduct of research involving human subjects, regardless of funding source.

 

I. Review all adverse events and unanticipated problems to subjects and others meeting local IRB criteria. 

 

J. Function as the Privacy Board by reviewing all HIPAA authorizations or requests to waive authorization for research undertaken at both UVM and FAHC.

 

K. Monitor active protocols to ensure compliance with the IRB-approved protocol and with applicable human subject protection guidelines and regulations.

 

 

 

3. CONTACTS

 

The administrative office of the Committees on Human Research is located in 245 South Park, Suite 900, 656-5040. 

 

Nancy Stalnaker

Research Protections Office Director

Nancy.Stalnaker@uvm.edu

(human subjects program management and

regulatory compliance issues)

 

Donna Silver

Research Protections Office Assistant Director

Donna.Silver@uvm.edu

(human subjects program management and

regularoty compliance issues)

 

Nancy Heller

Research Review Administrator

Nancy.Heller@uvm.edu

(protocol submission and review management for

Medical committee)

 

Gale Weld

Research Review Administrator

Gale.Weld@uvm.edu

(protocol submission and review management for

Behavioral committee and expedited medical)

 

Melanie Locher

Research Review Administrator

Melanie.Locher@uvm.edu

(continuing review and compliance monitoring)

 

Linda Warner

Research Review Assistant

Linda.Warner@uvm.edu

(pre-review of materials, data entry and followup of same)

 

Laurel Nolet

Research Review Administrator/System Specialist

Laurel.Nolet@uvm.edu

(Safety Subcommitee)

 

Kay Fay

Staff Assistant

Kay.Fay@uvm.edu

(data/records and website management)

 

 

Committee Chairs:

 

Deborah Rubin, M.D., Chair

Committee on Human Research in the Medical Sciences

Deborah.Rubin@vtmednet.org

 

David Kaminsky, M.D., Associate Chair

Committee on Human Research in the Medical Sciences

David.Kaminsky@uvm.edu

 

Theodore Marcy, M.D., Chair

Committee on Human Research in the Behavioral Sciences

Theodore.Marcy@uvm.edu

 

Katharine Sheperd, Ed.D., Associate  Chair

Committee on Human Research in the Behavioral Sciences

Katharine.Sheperd@uvm.edu

 

 

 

4. DETERMINATION IF PROJECT IS CONSIDERED RESEARCH OR INVOLVES HUMAN SUBJECTS

 

A.  Before developing a proposal for research activity, you need to answer two critical questions about it:

 

1. Is the activity in which you will be engaged RESEARCH?

2. Will the activity involve HUMAN SUBJECTS?

 

Federal Regulations (45 CFR 46: HHS Policy for the Protection of Human Research Subjects) provide the following definitions on which to base an initial decision.

 

1. RESEARCH:  "A systematic investigation including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge." 

2. HUMAN SUBJECT:  "A living individual about whom an investigator (whether professional or student) conducting research obtains (i) data through intervention or interaction with the individual or (ii) identifiable private information."

3. INTERVENTION: "...includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes."

4. INTERACTION:  "…includes communication or interpersonal contact between investigator and subject."

5. PRIVATE INFORMATION:  "…includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical or school record)."

 

1. Is the activity in which you will be engaged RESEARCH?

 

Is the activity designed to produce generalizable knowledge? In other words, will the information derived from the activity be applicable to other cases?  Will the information be gathered systematically? In other words, will it be arranged so that conclusions can be drawn, and so that others can review those conclusions?

 

Note:  Intent to publish results of an activity nearly always means it is research.

If there are no human subjects, with the exception noted above, involved in research as per the definitions above, the project usually may proceed without any Committee contact.  If there are questions regarding applying the definition, consult with IRB.

 

When might the activity not be considered research?

 

- Quality Assurance

All actions taken solely to ensure that standards and procedures are adhered to and that delivered products or services meet performance requirements.

 

Activities conducted solely for the intent of maintaining or improving quality of services provided by an institution (UVM, FAHC, etc.) are not considered research activities. However, if the data collected are generalizable and are to be shared outside of the institution through discussion, presentation, or publication, the activity qualifies as research.

 

Journalism - the periodical collection and publication of current news

 

Oral History

Most oral history projects do not need IRB review.  We make decisions whether or not an oral history project needs IRB review by whether or not the project also meets the definition of "research" found in the human subjects protection regulations.  This definition is:

 

§46.102 (d) Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

 

There are many oral history projects that are not research projects.  Those are generally projects that involve data gathering practices with the purpose of documenting a specific historical event or the experiences of individuals without the intent to draw conclusions or to generalize findings.  Oral history projects that are not research do not require IRB review or approval.

Conversely, there are research projects that involve the use of oral history methodology - those projects are not as common, but would need IRB review and approval.  The following are links to additional guidance for determination of whether a project is research and the corresponding form that can be found on our website:  http://www.uvm.edu/irb/inst-guide-template/not_research_determination_flow.pdf and http://www.uvm.edu/irb/?Page=m1_forms.php&SM=humanmenu1.html. 

 

Exercises Performed Solely Within a Classroom without intent to publish*

 

Marketing and Assessment Surveys without intent to publish*

 

Educational Assessments without intent to publish*

 

Case Studies – The IRB has defined a case study as a retrospective analysis of one, two or three clinical cases.  Publishing retrospective case studies does not constitute research, and therefore, does not require prior IRB review and approval.  However, investigators need to keep in mind that if there are any individual identifiers associated with the protected health information to which HIPAA applies, patients may need to provide authorization for use of their data.  You may use the FAHC Authorization template for this non-research purpose but its’ use does not require IRB review.

 

NOTE: If you intend to publish, the results will be ‘generalized knowledge’ and the exercise is RESEARCH.

 

If the answers to the questions are NO, then your proposed activity does not meet the definition of RESEARCH; therefore the FWA does not apply to the activity and the IRB does not need to review the activity.

 

If the answers to the questions are YES, then your proposed activity meets the criteria for RESEARCH. Now you need to ascertain if the research involves HUMAN SUBJECTS.

 

2. Will the activity involve HUMAN SUBJECTS?

 

Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains

 

- data through intervention or interaction with the individual, or

 

- identifiable private information.

 

ADDITIONALLY, THE DEFINITION OF HUMAN SUBJECT INCLUDES:

 

- research involving previously collected data or tissue specimens that are identifiable.

 

NOTE: Research that involves only coded private information or coded biological specimens may not constitute human subject research under regulations if

 

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

 

- The investigators on the proposed research cannot readily ascertain the identity of the individuals to whom the coded private information or specimens pertain (access to subject identities are prohibited by written repository procedures or a written agreement between the repository and the recipient researcher).

 

The determination of "research not involving human subjects" has to be made by the IRB not the investigator.  See Attachment I and Attachment J for additional guidance regarding “Research Involving Coded Private Information or Biological Specimens.”

 

If human subjects are involved in the proposed research activity, as per the definitions above, utilize the “Protocol Exemption Review and Determination Checklist” on our forms page to assist in establishing which type of review is required.

 

B.  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. 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.  Therefore, investigators should submit the Initial Administrative Review of an Umbrella Grant or Projects to be Developed form.  This will allow the IRB to certify what is in the grant with the caviat that not all activities specific to human subject involvement have been reviewed.  This will allow the release of grant funds so that work may begin. 

 

However, no human subjects may be involved until a human subjects protocol has been reviewed and approved by the Committee.  This new certification would be the approval of record going forward and you may be required to submit this to the funder.  

 

 

5. TRAINING REQUIREMENTS

 

 

6. NON-FACULTY RESEARCHERS WHO CONDUCT HUMAN SUBJECT RESEARCH

 

 

6.A. Use of Human Subjects by UVM Students  

 

 

7. TYPES OF COMMITTEE REVIEWS

 

See Attachment D for the IRB policy on fees.

 

7.A. “Full” Committee Review

 

One or more Committee member(s) are assigned to review the complete protocol or amendment, consent form, Investigational Drug/Device Brochure and any other protocol materials.  They summarize the protocol or amendment for the full Committee at a convened meeting and answer questions during the discussion. Committee members are provided summary information and the protocol consent form.  Members have the opportunity to review all other documentation related to the study as necessary. 

 

7.B. “Expedited” Review

 

Protocols, amendments, or continuing reviews that meet specific criteria outlined below qualify for an expedited review.  The complete protocol, consent form, and any other protocol materials receive review and approval by the Chairperson or one or more designated Committee members.

 

 

 

           

 

7.C. “Exempt” Research Review

 

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 Fletcher Allen Health Care 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.

 

To determine if your research qualifies for exemption from formal committee review, complete the “Protocol Exemption Review and Determination Checklist.”  This checklist will guide you as to whether it qualifies and what the next steps are.

 

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.  Where consent documents are used in exempt research, the consent document should be modeled after the consent template located on our website.  The investigator is responsible for ensuring that all the required elements are present in the consent form.  The IRB will check for these elements and stamp the consent form with an IRB exemption certification which will have no expiration date.  Exempt researchers are held to the same standards as non-exempt researchers.  These standards are found in section 10. 

 

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.

 

 

 

7.D.  “Research Not Involving Human Subjects” Review and Determination

 

Federal guidance states that there is a 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.

 

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.  See Attachments I and J for further guidance.

 

 

8. Submission Materials for Initial Review

 

As noted in the introduction, there are other departments or other entities within the University that are mandated to review human subject research.  In addition to the IRB, the following may apply.  The GCRC reviews only those studies for which the investigator wishes to utilize any of the GCRC resources.  The VCC reviews only studies related to cancer.  To assist in the submission process and avoid duplication of effort, the three committees developed combined submission instructions.  Please refer to our Protocol Submission Information for Research Involving Human Subjects to familiarize yourself with each of the committees’ requirements.   The IRB submission materials will be covered in this section.

 

8.A.  Protocol

 

One requirement for Committee review is a protocol.  Researchers may submit an industry-sponsored (written by industry) protocol, an investigator-written protocol, or use the Protocol Form which is available on our form page.  The Protocol 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 Committee strongly suggests that the Protocol Form be utilized any time a researcher is writing his/her own protocol, or when a grant is being submitted for review. 

 

8.A.1.   Elements

 

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

 

8.A.1.a.   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)

 

8.A.1.b.  Table of Contents (not a required element)

 

8.A.1.c.   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.

 

8.A.1.d.   Objectives. Clearly state the primary objective(s) of the study.

 

8.A.1.e.   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.

 

8.A.1.f.    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.

 

8.A.1.g.   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.  

 

8.A.1.h.   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).

 

8.A.1.i.    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.

 

8.A.1.j.    Human Subject Protections.  

 

8.A.1.j.1. 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 11.

 

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 11D.

           

8.A.1.j.2.  Recruitment/Informed Consent/HIPAA Authorization:  Describe plans for the recruitment of subjects and the process for obtaining informed consent, and HIPAA authorization (if applicable).  See Attachment B for guidance on compensation for subject participation. 

 

Include a description of the circumstances under which consent and authorization will be sought and obtained, the general information that will be provided to prospective subjects, and the method of documenting consent and authorization.  Where some or all of the subjects are likely to be vulnerable to coercion or undue influence, describe appropriate safeguards to protect the rights and welfare of these subjects.  See the section on recruitment and Attachment B for additional guidance.

 

If prospectively obtained and documented consent and authorization can not to be obtained from each and every subject or subject’s legal representative, then include a request for waiver or alteration of elements of informed consent and authorization and/or a waiver of documentation of informed consent and authorization using the Request for Waiver of Informed Consent/Authorization/Documentation form.

 

All advertising and recruitment materials, if applicable, must be included with the protocol for review.  See also recruitment.

 

NOTE:  Research subjects who are eligible for reimbursement from the research study through UVM are required to provide personal information such as name, address and social security number. This information along with the study name is forwarded to Procurement Services. At the first visit all the information noted above will be collected. Through the duration of their participation, only the last four digits of the social security number will be collected.

 

Research subjects who are eligible for reimbursement from the research study through FAHC have virtually the same process as above. The only difference is that FAHC 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.

 

 

8.A.1.j.3. 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.  In studies that involve interventions, describe the plan for data safety and monitoring of the research.  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.

 

8.A.1.j.4. Confidentiality:  A statement describing the extent to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Institutional Review Board and regulatory authorities may inspect the records.

 

8.A.1.j.5. 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; General Clinical Research Center protocols; 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.

 

8.A.1.j.6.  Adverse Event and Unanticipated Problem 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 “Adverse Event and Unanticipated Problems Reporting Policy and Procedures” will be followed.  The UVM/FAHC requirements for reporting adverse events and unanticipated problems to subjects and others should be included in the DSMP. 

 

For research protocols utilizing the UVM T3 research magnet, you must have a plan for handling incidental findings.  Refer to guidance on incidental findings in Attachment L.

 

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

 

8.A.1.j.7. 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.

 

8.A.1.j.8. Collaborating Sites.  When research involving human subjects will take place at collaborating sites or other performance sites when UVM/FAHC 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 Section 13.

 

8.A.1.j.9. Consent and HIPAA Authorization.  The consent form and HIPAA authorization (if protected health information (PHI) is included, (see Section 8.B for further information about PHI)) shall accompany the protocol as an appendix or attachment. 

 

8.A.1.j.10. References. Include references.

 

8.A.2.  Common Protocol Cover Form or Research Involving Human Subjects Determination and Exemption

 

These combined submission forms that are utilized by the Committees on Human Research, VCC and GCRC for the initial submission of protocols.

 

All the necessary forms and instructions for submission are located in the forms section of our website and should be downloaded each time you need one.  This will ensure that the most recent version is submitted.  Outdated versions will not be accepted.

 

 

8.A.3.  Blood Drawing Protocols

 

There is a category of expedited protocols that include only the collection of blood. Researcher’s conducting bench science often times require human cells for their laboratory research.  These researchers, as well as 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.  Follows is guidance for blood drawing protocols.

 

 

Guidance Blood Drawing Protocols Final 04/15/08

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 new Blood Drawing Protocol form have been developed to help standardize procedures to establish safe practices in the collection of human blood and human blood products for research purposes.                                                              Submission of the Blood Drawing Protocol for review and approval will assist the IRB in ensuring that donors’ who are participating are protected.    Blood Drawing 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:   Furniture – Blood draw chair or table should be made of materials that can easily be disinfected  (example vinyl or plastic furniture) 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. Disinfectant – Bleach solution or an EPA registered disinfectant should be available in the draw area in the event of a spill. Spill or Emergency Procedure - A procedure to handle spill cleanup or emergency response information should be posted at the point of use. Biohazardous Waste Disposal - Biohazardous waste bags and boxes must be used to dispose of all plastic ware and personnel protective equipment. 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. 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 bloodborne pathogen training on an annual basis.  Information on training is available on the University Environmental Safety website or is part of the Fletcher Allen mandatories.   Approved Standard Practices for Obtaining Blood   Healthy adults individuals will be asked to participate in this minimal risk procedure.  Education and review of the consent will be performed. After the consent is signed, the volunteer will be brought to ______________________ 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. The volunteer will be observed for any lightheadedness, bruising or bleeding during and after the procedure. If the volunteer is lightheaded, he/she will be reclined and monitored until symptoms resolve. If the volunteer is asymptomatic after the phlebotomy procedure, he/she will be released. 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.

 

8.A.4.  Biological Specimens/Data Repository Protocols

                       

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

 

NOTE:  UVM investigators sending data or specimens outside of the institution should contact the UVM Office of Technology Commercialization to determine if a Material Transfer Agreement or any other agreement defining the respective institutional responsibilities is warranted.

 

 

Biological Specimens/Data Repository Policy – 01-09 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.  Banking 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 means that identifying information (such as name or social security number) 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 “banking consent form”/authorization 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-purpose banking, 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 and 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 or Selling Tissue/Data to Other Researchers IRB review required: A UVM/FAHC 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/FAHC IRB, and the IRB has no jurisdiction over how non-UVM/FAHC 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/FAHC research, the IRB generally will not permit providing subject identifiers along with tissues or data to non-UVM/FAHC researchers. If necessary, the samples/data may be coded, but the key must be maintained at UVM/FAHC.  For those University of Vermont or FAHC 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/FAHC 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 banking (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 banking 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 for future research use, then the major part of the procedures and risks sections should discuss banking. 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 the banking 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.”

 

 

8.B.  Informed Consent/HIPAA Authorization 

           

8.B.1.  Consent Requirements/Elements

 

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

 

The information that is given to subjects should be in a language understandable to them or their representative.  Whether informed consent is written or oral, it should include no 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.

 

The Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for health insurance companies, group health plans, and most employers to discriminate based on a person’s genetic information.  All health insurance companies and group health plans must follow this law by May 21, 2010.  All employers with 15 or more employees should have been in compliance with this law as of November 21, 2009. 

 

GINA does not protect persons against genetic discrimination by companies that sell life insurance, disability insurance, or long-term care insurance.  GINA also does not prohibit discrimination on the basis of an existing genetic disease or disorder. 

 

Given that GINA has implications regarding the actual or perceived risks of genetic research and an individual's willingness to participate in such research, OHRP Guidance has indicated that investigators and IRBs should be aware of the protections provided by GINA as well as the limitations in the law's scope and effect.  They note that IRBs should consider the provisions of GINA when assessing whether genetic research satisfies the criteria required for IRB approval of research, particularly whether the risks are minimized and reasonable in relation to anticipated benefits and whether there are adequate provisions in place to protect the privacy of subjects and maintain the confidentiality of their data. GINA is also relevant to informed consent. When investigators develop, and IRBs review, consent processes and documents for genetic research, they should consider whether and how the protections provided by GINA should be reflected in the consent document's description of risks and provisions for assuring the confidentiality of the data.

 

If genetic materials are 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.

 

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 HIPPA 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 what is referred to as a HIPAA authorization.  The authorization must be signed by the subject prior to beginning research activities. 

 

The IRB provides instructions and a consent template to assist with consent form development.  FAHC, as the covered entity, has instructions and a HIPAA authorization template.   Use of the IRB consent template is strongly recommended whereas use of the FAHC authorization template is mandatory.  Refer to FAHC HIPAA policy.  These templates capture the basic and additional elements of consent as well as the required elements of HIPAA.  The elements are listed below.

 

Basic Elements of Informed Consent:

 

a. 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.

b. A description of any reasonably foreseeable risks (physical, psychological, social, legal, or others) or discomforts to the subject.

NOTE:  See section 8.A.1.j.3. Risks/Benefits, for additional information regarding GINA.  

c. 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.

d. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.

e. A statement describing the extent to which confidentiality of records will be maintained.

f. 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.

g. 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.

h. 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.

i. The name, address, and telephone number of the principal investigator(s) or contact person(s).

j. The amount of compensation, if any, for participation.

 

Additional Elements of Informed Consent:

 

a. 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.

b. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.

c. Any additional costs to the subject that may result from participation in the research.

d. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.

e. 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.

 f. The approximate number of subjects involved in the study.

g. 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.

 

 

Basic Elements of HIPAA Authorization:

 

a. States who the covered entities are.

b. What PHI will be used or disclosed by a covered entity.

c. Who within each covered entity may use or disclose PHI.

d. To whom a covered entity may disclose PHI.

e. How long a covered entity may use and disclose PHI.

f. Subject rights to access PHI associated with the research.

g. What occurs if subject does not sign an authorization.

h. Revocation of authorization.

i. What occurs once the PHI has been disclosed.

j. PHI and publications

k. Contact in case of questions.

 

8.B.1.a.  Ongoing Consent

                       

Over the course of a study new information may become available that may impact a subject's willingness to continue in a study. The Principal Investigator must consider the following questions:

 

1. How will new findings be communicated?

2. How will you determine if the subject is willing to continue study participation?

3. How will ongoing consent be documented?

 

The following are acceptable options for sharing new information.

 

1. Verbal Exchange

Information should only be shared in this way if it does not affect risk to subject.  The exchange can be conducted during a routine study visit or by phone.  Researcher needs to document discussion in the research record.

 

2. Informational Sheet

Information shared in this way typically does not substantially affect risk to subject.   This option does not require a subject signature, but the researcher needs to document that information was provided to the subject in a research record.  IRB review/approval is required prior to distributing to subjects.

 

3. Informed Consent Addendum

A consent addendum provides the subject with an update to the originally signed consent form.   This is option is typically used when there is a substantive change to the risk/benefit profile.   The addendum document includes only that information which is new or different from the originally signed document, reducing the potential for participant confusion.  The subject’s signature indicates their willingness to continue participation in the study given the new information.  Use of a consent addendum requires IRB review/approval and IRB stamp with an expiration date prior to use. Reviewed, signed and dated by the subject and the researcher in the same manner as the original consent document.

 

4. Full Consent

IRB policy is that a consent addendum be used instead of requesting the subject sign a full copy of the newly revised consent again.  Requesting that subjects sign a full consent every time there is a revision to the consent document is a practice that can confuse subjects unnecessarily. Changes to this policy will be reviewed on a case-by-case basis.

 

Note:  Consent form version numbers or dates 

The Committee requests that a consent form version number or date appear on the consent form document footer.  This assists both the investigator and the Committee in making sure that we are all working on the appropriate consent version for a specific amendment. 

 

Some sponsors, however, are requesting that investigators update their consent form every year at time of continuing review or with every protocol amendment, even if there have been no actual changes to language in the consent form.  The Committee does not allow this practice for the reason stated above.  The consent version number or date must remain the same if there have been no actual changes to the consent language.  When actual language changes are necessary as a result of new information, only then can the version number or date be changed.   

8.B.1.b.  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 IRB finds and documents that the required conditions for a wiaver of consent are met.  Complete and submit the “Request for Waiver of Informed Consent” form to the IRB for this determination. 

 

The IRB has created a sample consent for “Continued Participation in a Research Study” that should be used for consenting the now-adult subjects.  This consent form is essentially a continuation cover consent that explains why they are 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.  The 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 their parents 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 their parents or guardians were they still minors.

8.B.1.c.  Media Consent

 

If a subject consents to participate in a protocol and then agrees to be interviewed regarding their protocol 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 giving up that protection by agreeing to 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 can be found on our website in the forms section and should be completed by the subject prior to the interview.  The IRB does not require a copy.

 

8.B.2.  Consent Form/HIPAA Authorization Formats

 

For guidance in consent and authorization development, as well as templates for these two documents, see the forms section of the IRB website. 

 

8.B.3.  Requirements for Preparing Consent Forms and HIPAA Authorizations in Foreign Language

 

New Policy:  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.

 

For studies that will need the consent translated into another language, the standard operating procedure is to hold the translation until the IRB has approved the English language consent form.  Once the IRB has approved the consent form, a foreign language consent form can then be prepared and the following needs to be resubmitted for final approval of the foreign language consent form:

 

1. Original English version of the consent.

2. Foreign language version of the consent.

3. A letter describing the qualifications (e.g., Spanish speaking native or Vietnamese speaking native) of each translator and date of translation.

 

If the research is deemed “high” risk or is very complex, the IRB reserves the right to additionally request the following:

 

1.  A back translation from the foreign language back to English.  This will ensure that the foreign language consent contains all of the key elements.

2. A letter or a memo indicating that this translation was done by a different translator than the one who did the original translation.

 

Alternatively, 46.117(b)(2) permits oral presentation of informed consent information in conjunction with a short form written consent document (stating that the elements of consent have been presented orally) and a written summary of what is presented orally.  A witness to the oral presentation is required, and the subject must be given copies of the short form document and the summary.

 

At the time of consent, (i) the short form document should be signed by the subject (or the subject’s legally authorized representative); (ii) the summary (i.e., the English language informed consent document) should be signed by the person obtaining consent as authorized under the protocol; and (iii) the short form document and the summary should be signed by the witness.  When the person obtaining consent is assisted by a translator, the translator may serve as the witness.

 

The IRB must receive all foreign language versions of the short form document as a condition of approval under provision 46.117(b)(2).  Expedited review of these versions is acceptable if the protocol, the full English language informed consent document, and the English version of the short form document have already been approved by the convened IRB. 

 

Any necessary deviation from these alternatives requires review and approval by the IRB.

 

8.B.4.  Authorization Cover Form

 

The Authorization Cover Form is a form utilized by the Committees on Human Research to review HIPAA Authorization forms.  In this function, the Committees on Human Research are operating as the Privacy Board for FAHC, which is the Covered Entity.  Every HIPAA Authorization approved by the Committees/Privacy Board must have an Authorization Cover Form.

 

All the necessary forms and instructions for submission are located in the forms section of our website and should be downloaded each time you need one.  This will ensure that the most recent version is submitted.  Outdated versions will not be accepted.

 

8.B.5.  Waiver of Informed Consent, Alteration of Informed Consent, or Waiver of Documentation of Informed Consent

 

A.  Waiver of Informed Consent:  In some research, written or verbal consent is not possible.   A typical example would be retrospective record or pathology reviews.  Consent is not possible because the subjects are not available to sign a consent form.   Alteration of Consent:  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 debriefed after the research is complete. The requirement to obtain written or verbal informed consent may be waived 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.

 

NOTE:  The FDA does not typically allow for a waiver of consent when regulated test articles are being used.   Only in the case of emergency care will a wavier be considered, see below 8.B.5.B.

                                   

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. 

 

B.  Waiver or Alteration of Informed Consent: “Emergency Use” If your protocol includes an FDA regulated test article (drug or device), an exemption from the consent requirement is permitted for “Emergency Use” providing the additional following four conditions are met and certification of compliance is provided to the IRB by both the investigator and a physician who is not otherwise participating in the clinical investigation prior to use of the test article, if possible.

 

1) The human subject is confronted by a life-threatening situation necessitating use of the test article;

 

2) Informed consent cannot be obtained from the subject because of an inability to communicate with or obtain legally effective consent from the subject;

 

3) Time is not sufficient to obtain consent from the subject's legal representative; and

 

4) There is available no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject. (21 CFR 50.23(a))

 

If certification of compliance with the four conditions specified above cannot be obtained prior to using the test article, certification (See Attachment A) must be submitted to the IRB within 5 working days after the use of the test article.

 

The Committee is aware of the difficulty in addressing these issues; however, this is a specific regulatory requirement.

 

 

C.   Waiver of Documentation of Informed Consent:  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 lay summary about the research.  This written statement must be reviewed and approved by the Committee prior to use.  The principal investigator or a research team member must document in the research file that verbal consent was obtained.

 

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 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. 

 

8.B.6.  Waiver of Authorization

 

FAHC 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.

 

To apply for a waiver 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 the waiver is granted, then the waiver approval signed by the IRB chair or designee shall be forwarded to the Principal Investigator. 

 

8.B.7.  Request for Waiver of Informed Consent /Authorization/Documentation Form

 

Note:  The Request for Waiver of Informed Consent /Authorization/Documentation Form is a form utilized by the Committees on Human Research to review the specifics of any requested waiver of normally required research materials.   Every waiver approved by the Committees must have submitted a Request for Waiver of Informed Consent /Authorization/Documentation Form. If you are applying for a waiver of both consent and authorization, only one form need be completed and submitted. 

 

All the necessary forms are located in the forms section of our website and should be downloaded each time you need one.

 

 

8.B.8.  Request for a Partial Waiver of Authorization for Recruitment Purposes

 

Recruitment of potential research subjects at FAHC/UVM is a regulated research activity and must be conducted in accordance with the policies and procedures promulgated by the UVM Institutional Review Board.

 

FAHC may use or disclose PHI for the recruitment of FAHC patients into a research study without authorization or an IRB waiver of authorization only if such recruitment is performed by a “FAHC Health Care Provider” who has a “direct treatment relationship” with the patient. 

 

Note:  For purposes of this policy, a “FAHC Health Care Provider” is defined as a licensed health care professional who is employed on a full-time or part-time basis by FAHC, regardless of whether or not the provider holds a faculty appointment at UVM or has an employment relationship with UVM.  For purposes of this policy, a “direct treatment 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.

 

A FAHC provider or his/her agent may, without patient authorization or an IRB waiver of authorization, review the medical records of patients with whom he or she has a direct treatment 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.

 

Note:  For purposes of this policy, an “agent” is defined as an individual who is under the direct supervision and control of the FAHC 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, FAHC 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.

 

8.B.9. Request for Partial Waiver of Authorization for Recruitment Purposes Form

 

Request for Partial Waiver of Authorization for Recruitment Purposes Form is a form utilized by the Committees on Human Research, which are operating as the Privacy Board for FAHC, 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.

 

Note:  All the necessary forms for submission are located in the forms section of our website and should be downloaded each time you need one.

 

8.B.10.  “Legally Authorized Representatives” for Provision of Consent for Research in Emergency Settings

 

 

 

 

8.B.11.  Guidelines for Non-Emergent Research Involving Individuals with Questionable Capacity to Consent

 

 

8.B.12.  Documentation: 

 

The PI must keep a copy of all forms/documents submitted to the IRB (perhaps in a Research Regulatory Binder) as evidence of IRB submissions and approval record.

 

NOTE:  Initial protocol approval periods begin on the date the protocol was reviewed by the fully convened IRB, not on the date the IRB chair or designee verifies that IRB-specified conditions for approval have been satisified.

 

8.C.  Review of Grants/Contracts/Review Fees

 

RPO, Pre-Award Services 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 Pre-Award Services and 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 or study incentives).  Protocol approvals are not released until applicable contracts have been fully executed. 

 

8.C.1.  New Competing or Competing Renewal Grant Applications

 

To meet the requirement listed above, any time you will be submitting a new competing grant or a competing renewal application, a new protocol must be submitted to the IRB for review and approval.  Pre-Award Services will not clear funds for release until there is an approved protocol.  Continued approvals will be checked on an annual basis for the life of the grant.  

 

Note:  It is very important that the proposal and protocol be matched correctly for the reason mentioned above and to ensure that the required reference to the sponsor made in the consent form is accurate. 

 

8.C.2.   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)/Authorization (if applicable).

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 CHRBS/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.  Refer to Protocol Submission Information.

 

8.C.3.  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.

 

8.C.4.  Just-in-Time Provision for IRB Submissions

What is “Just-in-Time” Review

The NIH just-in-time policy allows grant applications to be submitted to NIH for peer review without prior IRB approval.  This policy has been extended by the University to all UVM grant proposals where the granting agency does not require IRB approval at the time the proposal is submitted.  Researchers should check with the Pre-Award Services Office to determine the funding agency’s IRB approval requirements.

 

Process for “Just-in-Time” Review

If the sponsor accepts just-in-time human subjects review, as soon as the researcher is notified that the proposal received a favorable priority ranking from the granting agency, the protocol should be submitted to the IRB for review.   If the project is a new or competing renewal and is identical or substantially similar to a previously approved protocol, see section 8.C.2. for further guidance.  If the project is not identical or substantially similar, researchers should check the IRB submission deadlines for the next available IRB meeting as special requests for insertion onto an agenda after the scheduled deadline may not be possible.  NOTE:  It is not necessary for the researcher to submit a protocol if the priority ranking is unfavorable. 

 

If the just-in-time request is for a resubmission, see section 8.C.3. for submission guidance.

 

The delay in submission of a protocol for IRB review approval may delay an award but should not affect the receipt of an award.

 

8.C.5.  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.  These applications may not need to be reviewed by the Committee before an award can be made by DHHS or another federal agency.  Examples of this may include activities such as research training programs, research, pilot, or developmental projects in which human subjects' involvement will depend upon development of instruments or pre-clinical animal studies.

 

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. 

 

8.C.6.  Contracts

 

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 be in place between the sponsor and either UVM or FAHC.  Most industry-sponsored research contract review is done through the Office of Clinical Trial Research (OCTR) however a  select few are handled through Pre-Award Services (PAS).

 

The IRB requires a copy of the final contract prior to release of a protocol approval.  OCTR/PAS 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.

 

8.C.7.  Review Fees

 

                        Refer to fee policy in Appendix D.

 

8.C.8.  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 lists the following actions as those requiring approval before they are made.

 

·        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, e.g., changing assays from those approved to a different type of assay.

·        Transfer of the performance of substantive programmatic work to a third party if the third party is a foreign component.

·        The following changes in the involvement of the principal investigator or other key personnel named in the award notice: Withdrawal from the project entirely, an absence from the project during any continuous period of three-months or more, or reduction in time devoted to the project by twenty-five percent or more from the level that was approved when the project was awarded.

 

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 OSP Pre-Award Services 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.

 

 

9. Submission of Materials After Initial Approval is Obtained

 

      The following are materials that require submission after initial approval.

 

9.A. Continuing Review

 

9.A.1.  Requirements

 

Federal Policy: Continuing review of research activity is required by federal regulations [(45CFR46.109 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: (updated 11/11)

 

In order to resolve the issue of indefinitely reviewing and reapproving protocols annually for which work has not ever been started and wasting valuable staff and IRB reviewer time, 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 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.

 

The majority of protocols that we have been reviewing and reapproving for many successive years actually never get started.  If the work was to begin many years after submission, the original forms and protocol would likely be outdated and it would be beneficial for the protection of human subjects to give the project a new review. 

 

9.A.2.  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

OHRP Guidance Released November 10, 2010 K.  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: o  Identifiable private information obtained by interacting or intervening with the human subjects; o  Identifiable private information stored in documents, records, photographs, images, video recordings, or audio recordings provided to the investigators from any source; o  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; o  Identifiable private information obtained about an individual by interviewing other people (e.g., an individual’s healthcare provider or teacher); o  Identifiable biological specimens provided to the investigators from any source; or o  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 is completed or no longer involves human subjects. The PI must can 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 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.

 

The most visible element of the continuing review process is the stamped IRB approval date on the signature page of the consent form.  The date expires every year (or sooner for those requiring review less than annually) and can only be extended through the Continuing Review process.

 

9.A.3.  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.  All forms are located in the forms section of our website and should be downloaded each time you need one. Incomplete forms will be sent back to the investigator.

 

9.A.4.  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 interoffice mail. 

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); and

iv. Copies of all additional documentation submitted to the Committee at the time of Continuing Review. 

 

c. Stamped Consent Forms: Copies of the newly approved consent form with the Committee stamp and the expiration date should be made directly from the copy placed in the research binder.  These copies must be used for all new subjects. 

d. All previous unsigned versions of the consent form should be destroyed (with the exception of a copy in the Research Binder) to prevent the accidental use of expired consent forms. 

 

**** The single most important practice to ensure compliance with the continuing review process is that the consent form given to subjects is current (i.e., with a Committee stamp and an expiration date which has not expired) ****

                                                         

9.B.  Adverse Event and Unanticipated Problems Reporting

 

9.B.1.  Policies

 

a)  Federal Policy:  Review of unanticipated problems involving risk to subjects or others (hereinafter referred to as unanticipated problems) is required by federal regulations (45CFR46.103 section 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. 

 

b) Local Policy: (below)     

 

 

 

                        9.B.2.  Determining When to Report Local Unanticipated Problems: 

 

The following flowchart is a tool for determining which local unanticipated events require reporting.  The IRB may categorize a protocol as “higher risk” and require the Investigator to report all local adverse events promptly to the IRB, regardless of whether the event is related or expected.  This determination will be made at time of initial review or anytime after initial review if the IRB feels it is warranted.  This determination and the requirements will be clearly communicated back to the Investigator. 

 

NOTE:  Child abuse that is revealed as part of the research is not reportable to the IRB.  Handling is discussed in the protocol and the required reporting is covered in the consent form.  The IRB does not require notification of these cases.

 

  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

      9.B.3.   The Local Report for Serious & Non-Serious Adverse Events Form

 

Note: All the necessary forms are located in the forms section of our website and should be downloaded each time you need one.

 

The Local Report for Serious & Non-Serious Adverse Events Form captures all of the required elements for a significant review of adverse events.  The initial report must be submitted by the deadlines in the policy even if there is insufficient information for a complete report.  If there is insufficient information, please check “Initial Report” and state that a “Complete Report will Follow”.  Submit all supporting information available at the time of initial submission.   The “Follow-up Report” should be submitted as soon as additional information is available.   

 

 

9.B.5.   Amendments to Protocol Submitted Due to New Safety Information

 

Amendments and addenda to a research protocol may be submitted at the same time new safety information is reported.  A Request for Modification/Amendment Form describing the changes and all appropriate documentation (revised consent form, and/or revised protocol as appropriate) must accompany the appropriate Safety Form.  An investigator cannot implement amendments prior to the review and approval of the Committee.

 

9.B.6.  Documentation 

 

a. The PI must keep a copy of the Local Report for Serious & Non-serious Adverse Events Form (perhaps in a subject’s Research Binder) as evidence of IRB submission. 

 

b. It is the Committee’s policy not to provide verification of receipt of local adverse events, unanticipated problems, deviations or other safety updates.  A copy of this policy may be forwarded to those sponsors who request that receipt be obtained.

 

9.C.  Request for Modification/Amendment to Previously Approved Protocol

 

9.C.1.   Requirements: 

 

Review of any changes to previously approved research is required by

federal regulation [45CFR46.103(b)(4)] and is an essential element of the continuing review of research involving human subjects.  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 [FDA: 21CFR56.108(a)(4)].

 

Immediate Hazard:  The definition for 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 Report of Serious Adverse Event or Unanticipated Problem 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.

 

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.

 

Major modifications/amendments potentially affecting the risk/benefit ratio are 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 for or providing the subjects with an informational sheet regarding the update (see 8.B.1.a Ongoing 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.  The IRB shall determine on a case-by-case basis when such notification, and its documentation, is required.

 

The amendment review process does not affect continuing review expiration dates. 

 

9.C.2    When to Request

 

Requests for approval of modifications may be submitted at any time.  Complete a Request for Modification / Amendment to Approved Protocol form.  The changes must be approved, before any changes can be implemented in the conduct of the protocol.  If the amendment requires a revision to the consent form, the consent approved with the amendment will now have a letter designation added to the IRB stamp.  This helps to track which consents apply to which version of the approved protocol.  There will be no letter designation if the Request for Continuing Review form and the Request for Modification / Amendment to Approved Protocol form are submitted together and approved at the same time.

 

9.C.3.   The Request for Modification / Amendment to Approved Protocol Form

 

The Request for Modification / Amendment to Approved Protocol form is intended to capture all of the required elements for a significant review of changes and amendments.  When submitting amendments, you are not required to resubmit the entire protocol. Submit a completed Request for Modification / Amendment to Approved Protocol form to the Committee with all supporting documents that have been modified (i.e., protocol pages, questionnaires, recruitment flyers, consents, etc.). 

 

Note: All the necessary forms are located in the forms section of our website and should be downloaded each time you need one.

 

Please Note:   The GCRC and VCC also require review of changes to protocols under their purview.  Please see our forms section for further guidance.

 

9.C.4.   Documentation: 

 

Once approved, the Committee will return a signed Request for Modification / Amendment to Approved Protocol form and a stamped consent form/authorization form (if applicable) to the PI via interoffice mail.  Proof of the amendment/change approval as well as the stamped consent form/authorization form must be kept by the PI (perhaps in a Research Regulatory Binder) as evidence that the Committee has approved the change. 

 

Note:  The newly revised consent form will have the same expiration date (if not outdated at the time of amendment request) as the pre-amendment consent form.  There will now be an identifying letter along with the expiration date.  This letter is associated with the approved amendment.   Care must be taken to verify that the most current version is being used.

 

9.D.  Notice of Protocol Closure or Request to Reopen a Closed Protocol

 

Investigators have the responsibility to formally close a study with current IRB approval once it is completed or discontinued.  A protocol can only be considered completed once all subject interventions are complete, all follow-up has ceased, and the data analysis is final.  Notification must be done by completing a continuing review form.  This provides the opportunity for the researcher to summarize all the activities into a final report.  Researchers cannot use an amendment form to close a protocol.

 

If the investigator needs to reopen a protocol and it has been less than one year after 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. 

 

Note:  If the investigator is leaving the institution, it is the investigator’s responsibility to contact the IRB to discuss their institutional status in regards to ongoing research activities and to close or appropriately transfer protocols before their departure.  If this is not accomplished prior to leaving the institution, all protocols may be administratively closed by the IRB.  See above requirements if a protocol needs to be reopened after an IRB administrative closure.

 

10. Investigator Responsibilities

 

10.A.  Expectations of an Investigator

 

There are certain expectations of a principal investigator (PI).  When the principal investigator submits a research study to the IRB, by signing the Common Protocol Cover Form they agree to the expectations listed below:   

 

 

Subinvestigators have an equally important role in that they are often assigned with the day-to-day conduct of the study. 

 

All investigators participating in industry sponsored research should be aware and adhere to the Good Clinical Practice guidelines.  Additional information regarding GCPs can be accessed at http://www.fda.gov/oc/gcp/default.htm.  Our statement of compliance with GCPs can be found in Appendix F.

 

10.B.  Requirements of the Principal Investigator

 

As the principal investigator you must:

 

Ensure proper training of the research team;

Ensure protocol adherence;

Create a process of informed consent; and

Provide reports on the progress of the study.

 

10.B.1.  Ensure Proper Training of the Research Team

 

The principal investigator is responsible for ensuring that the research team has appropriate training prior to and during the conduct of the study.  All research team personnel are required to complete the Protection of Human Subjects in Research tutorial.  They also need to have specific training for the given protocol.  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. 

 

10.B.2.  Ensure Protocol Adherence

 

It is the principal investigator’s responsibility to ensure that the IRB-approved protocol is being followed by the research team.  This includes making sure that amendments are submitted for IRB review in a timely fashion and then once approved implemented by the research team.

 

10.B.3.  Create a Process of Informed Consent and HIPAA Authorization

 

Informed consent is one of the basic ethical obligations for all research involving human participants.  Informed consent is not just a form.  It is a process of information exchange that takes place between the subject and the investigator or the study team, before, during and sometimes after the completion of the study. The amount of information that needs to be presented both in writing and verbally is directly related to the risk that the study presents and the complexity of the study design and related procedures.

 

The information in the HIPAA authorization conveys how the institution will use and disclose the subjects’ protected health information in the context of the research study.  Some research studies do not use protected health information and therefore would not need an authorization.  For purposes of this discussion, authorization will be included along with the consent. 

 

The manner and context in which information is conveyed is as important as the information itself. There must be no coercion or undue influence. Potential subjects must have sufficient time to decide and should be allowed to consult with family and/or others if needed.

 

The purpose of a consent form and authorization form is to provide a written source of information and documentation that a subject’s consent and authorization has been obtained.  Consent forms and authorization forms must be signed and dated by the subject prior to conducting any research related procedures or data collection.

 

The IRB reviews the consent form and authorization form to ensure that it contains required information in sufficient detail to protect the rights and welfare of human research subjects.  The IRB stamps its approval on these documents.  Form templates are available on our website under the forms section.

 

NOTE:  The approval and expiration dates refer to the dates that the consent may be used for new subject enrollment and do not refer to the expiration of the document as far as validity is concerned.  The subjects would only need to be re-consented if the document was revised significantly.  The originally signed and dated consent document (as long as it was valid at the time it was signed, i.e., currently approved version) is valid for the entire time period the subject participates in the research.

 

The approved authorization form does not have an expiration date and is good until the study closes or substantial revisions to the form are necessary.  If changes are made a new approval date is placed on the revised form. 

 

The investigator should be certain that the most current IRB approved consent form and an approved authorization form is being used at all times.  To that end the PI should develop a system with the research team to avoid the use of outdated forms.

 

 

a.   Obtaining informed consent:

a. Written informed consent and HIPAA authorization, when applicable, has to be obtained from every subject who enters a research study, before any study related procedures are undertaken.

b. The subject should be provided the information outlined in Section 8.B., both verbally and in writing.

c. Once the subject has decided to participate, both the person obtaining consent and authorization (when applicable), and the research subject should sign and date the form(s).

d. The subject must receive a signed and dated copy of all executed documents, including subsequent updates to the consent.

 

b. Delegating the informed consent process:

The principal investigator may delegate the consent and authorization process to an appropriately qualified person.   This person must be listed on the protocol as key personnel and have taken the required human subjects training.  Consider the complexity of the protocol and level of risk when designating responsibility for obtaining informed consent.

 

c.    Documentation of informed consent:

The signed informed consent form is documentation and must be retained.  For some clinical trials, the discussion with the subject regarding potential participation and the informed consent process must be documented in a source document.  The most likely source document would be the medical record, but could also be a note to the research record. 

 

10.B.4.  Provide Reports on the Progress of the Study 

 

During the course of a research study, new information might become available about safety or the study population under investigation.   As new information becomes available, the principal investigator is obligated to report to the IRB.    Common items that need to be reported in a timely fashion to the IRB are described in detail below

a. Continuing review of approved studies

It is the responsibility of the principal investigator to submit the current status of active protocols at least annually.  Some protocols require more frequent review based on risk.  The IRB makes this determination and notifies the principal investigator.  Please refer to Section 9.A. for additional information on submission of continuing reviews.

b.  Reporting adverse events,  deaths and unanticiapated problems to subjects or others

Refer to Section 9.B. for reporting information.

c.  Amendments to a previously approved protocol

Any changes to the protocol, consent form or recruitment materials require IRB approval.  Requests for changes (amendments) to approved studies may be submitted at any time but before the change is implemented, it must receive IRB approval.  Refer to Section 9.C. for further instructions on how to submit an amendment.

d. Development of subject recruitment and retention materials

Recruitment strategies are very important to the success of a protocol and often change over the course of a protocol.  Recruitment and retention materials (e.g., advertisements, flyers, letters) need to be submitted for IRB review and approval.  If the materials require posting, the Committee needs to know where the materials will be posted.  Materials cannot be used until IRB approval has been provided.  When submitting recruitment material(s) with new protocols, check the appropriate box on the Common Protocol Cover Form and attach the materials for review.  When materials are submitted after the initial submission, complete the Request for Modification / Amendment to the Approved Protocol form and attach the materials for review.  Below are IRB guidelines for recruitment materials. See recruitment.

e.  Change in research team

It is required that the investigator notifies the IRB office when there are any additions or deletions to research staff participating in a protocol.  Update the current key personnel list by completing a Request for Modification/Amendment to Approved Protocol form.

 

All key personnel are required to take the Protection of Human Subjects in Research tutorial before their active participation on the protocol and every 3 years thereafter.  Refer to Section 5 to learn more about required training. 

f.  Premature termination/suspension

The IRB should be notified when a protocol has been terminated or suspended prematurely. The IRB also needs to know the reason for premature termination or suspension.   To notify the IRB complete the Request for Modification / Amendment to the Approved Protocol form and send to the IRB office. 

g.  Study closures or requests to reopen closed protocols

See Section 9.D. for reporting requirements. 

 

10.B.5  Coverage for PI or Faculty Sponsor

 

In order to fulfill the PI or faculty sponsor responsibilities, the IRB must be notified when a sabbatical or extended leave of absence of more than four weeks will be taken. IRB notification needs to include a designated investigator who will comply with the requirements noted above.  This does not apply when the investigator or faculty sponsor does not have active protocols for which they are responsible.

 

10.B.6  Investigator’s Responsibilities when Leaving the University

 

If the investigator is leaving the institution, it is the investigator’s responsibility to contact the IRB to discuss their institutional status in regards to ongoing research activities and to close or appropriately transfer protocols before their departure.  If this is not accomplished prior to leaving the institution, all protocols may be administratively closed by the IRB. 

 

10.C.  Guidance for the Investigator

 

10.C.1.  Communication with the IRB

 

When you are in communication with the office, whether in writing, by telephone, fax or e-mail, you should have the following information available.

 

- CHRMS or CHRBS number, if assigned at time of contact

- Principal investigator’s name

- Protocol title

- Date and type of submission (if applicable)

 

We cannot readily assist you without this information.

 

All submissions must be in paper form and may be submitted by:

 

1) Inter-departmental mail for on-campus personnel:

 

Research Protections Office

245 South Park, Suite 900

 

2) US Postal Service for off-campus personnel:

 

Research Protections Office

UVM Committees on Human Research

245 South Park, Suite 900

Colchester, VT 05446

 

3) Hand Delivery to the IRB office:

 

Research Protections Office

245 South Park, Suite 900

Hours: 8am – 4:30 pm (Monday – Friday)

 

10.C.2.  Written Communication of IRB Decisions

 

Decisions made by the IRB will be communicated to the principal investigator (or designee if provided) through a memorandum outlining the approval status and/or concerns, questions and/or comments of the IRB. 

 

NOTE:  Initial protocol approval periods begin on the date the protocol was reviewed by the fully convened IRB, not on the date the IRB chair or designee verifies that IRB-specified conditions for approval have been satisified.

 

The IRB Chair will convey one of the following four decisions in writing to the investigator promptly after the meeting:

1. Approval 

The principal investigator may begin the research study upon written notification of approval of the research protocol and the informed consent form (if applicable) from the IRB chairperson.  A HIPAA authorization form (if applicable) will also be included.

2. Approval Withheld Pending Clarifications

This decision is determined when the protocol is recommended for approval by the IRB pending the investigator’s response to IRB-directed questions and/or revisions.  The principal investigator must provide a memorandum responding to the IRB’s recommendations. We ask that you indicate the CHRMS/CHRBS number on this correspondence and attach a revised protocol (if applicable), revised consent form (if applicable), and a revised HIPAA authorization form (if applicable). 

3. Tabled

More substantive issues regarding the protocol and/or consent form must be addressed.  Clarifications or requested revisions may have a significant impact on subject safety or understanding.  A memorandum is sent to the investigator requesting that these issues be addressed.  Full committee review of the investigator’s response is required prior to approval.

4. Disapproved

Questions regarding the rights and welfare of the subjects are of such significance that the committee finds approval of the study to be unwarranted. The authority of the Committee on Human Research to disapprove a human research study may not be overridden.

 

NOTE:  The IRB has a 30, 60, 90 day reminder system for all pending protocol items.  The investigator is reminded that the IRB has requested something from them in regards to a protocol and is awaiting his/her response.  At the 120 day mark the protocol is withdrawn from the Committee’s consideration.  This helps to ensure that changes to protocols are handled in a timely fashion.

 

10.C.3.  Retention of Research Records

At a minimum research records should be retained for 3 years after research is complete. This meets the federal requirements for IRB protocol file records.  UVM’s policy on Data and Retention for Externally funded research may require a longer period (3-5 years).  See UVM Data and Retention Policy

http://www.uvm.edu/policies/general_html/recordretention.pdf.

 

There also may be additional requirements from sponsors such as:  the investigator is required to maintain a file of study records, including informed consent documents, for at least two years after the last approval of a marketing application (ICH Guidelines for GCP, 4.9.5).  If clinical development is discontinued, or an NDA is not submitted or is later disapproved, study records must also be retained for at least two years after the termination of the investigation. 

 

It is the responsibility of the sponsor to inform the investigator when research documents no longer need to be retained (21 CFR, 312.62).  However, when no sponsor exists, it is up to the investigator to maintain research records as referenced above.

 

When the retention period has been met and materials are to be destroyed, we recommend that paperwork be shredded for confidentiality purposes.

 

10.C.4.  Accessibility of Records

The investigator must make available all research records for direct access by 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, VCC, GCRC, FAHC 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.

 

10.C.5.  Human Subject Recruitment/Retention Guidance

A basic tenet of human subject research, as required in federal regulations, is that the selection of human research subjects be equitable.  That is, special subgroups of the population should not have to bear a disproportionate amount of the risks of research that benefits others; subjects of an investigation should not come from any particular group simply because it is convenient for the researcher to draw from that group.  In addition, subgroups should be provided equal access to the benefits, which may result from the research. 

 

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

 

Common methods of human subject recruitment follow:

PI/Collaborators recruit own subjects

Any FAHC health care provider or his/her immediate practice group who has a direct treatment relationship with the patient may recruit for an IRB-approved protocol.

PI sends letter to colleagues asking for referrals of eligible patients who are interested in the research study

The referral letter and process needs IRB approval prior to use.  This recruitment strategy depends on the potentially interested subject to contact the researcher.  The researcher cannot contact the potentially eligible subject(s) directly, since a treating relationship does not exist.

 

PI sends letter to colleagues asking these physicians to send out the “Dear Patient” letter describing the research study

The “Dear Patient” letter and process needs IRB approval prior to use.  The interested subject must contact the researcher. The researcher cannot have access to the patient names or addresses for mailing purposes.

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 waiver of the HIPAA authorization requirement.  This 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.  Further IRB review and approval would be necessary to allow removal of information or to further contact potential patients.  Complete Request for Partial Waiver of Authorization for Recruitment Purposes form if you wish to waive authorization to review information.  Please refer to Section 8.B. for additional HIPAA information.

 

Advertisements or Media

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, advertisments 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 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 Campaigns

 

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. 

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 of students;

- Avoiding any personal solicitations of students by faculty, graduate assistants, or fellow students; or in the case of employees, utilizing a third party unassociated with the relationship is the best strategy;

- 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 may be more than minimal risk.  The IRB, however, may reconsider this practice on a case-by-case basis.

 

Subject Retention

It is understood that many studies require long-term followup for disease and survival data.  The protocol should account for this followup 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.

 

Note:  It is the Committee’s practice to require that minor subjects be compensated with savings bonds or appropriate gift certificates rather than cash.  Accordingly, the compensation sections needs to be revised to reflect that.  If savings bonds are to be used, it should be clear whether the amount of compensation is the purchase amount of the bonds or the face value (maturity value).

 

Also see Attachment C for further guidance on the IRB Policy on Finder Fees.

 

10.C.6.  Investigator Financial Interest

 

 

 

11. Additional Protections For Special Populations

                       

11.A. Guidelines 

 

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 and Fetuses;

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. Cognitively impaired subjects;

5. Mentally ill subjects (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

6. Subjects with drug and/or alcohol addictions (certificates of confidentiality are strongly recommended for this group);

7. Subjects with other disabilities; or

8. 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. 

 

11.B. Pregnant Women, Fetuses, and Neonates

 

11.B.1.  Pregnant women 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 pregnant women and fetuses, if appropriate;

2. If there is the prospect of direct benefit for the woman or the fetus; the risk to the fetus is caused solely by interventions or procedures,

3. If there is no prospect of benefit for the woman or 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 (and HIPAA authorization, if applicable) 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.

 

11.B.2.  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 11.D. (Children)

 

11.B.3.  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.

 

11.C. Prisoners

 

Consult 45 CFR 46 Subpart C (Sections 301, 302, 303, 304, 305 and 306)

 

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.

 

11.D. 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.

 

PLEASE 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.

 

Consent: 

The consent process of children should meet the following Requirements for Assent and Parental Permission (in addition to a HIPAA authorization if applicable):

 

Assent is a child's affirmative agreement to participate in research. Failure of a child to object to participation should not be construed as assent.

 

Adequate provisions should be made for soliciting the assent of children when they are capable of providing assent. In determining this capability, the age, maturity and psychological state of the child involved should be taken into account. It is generally agreed that children 11 years of age and older should grant assent.***

 

Permission is the agreement of a parent (s) or guardian to the participation of their child or ward in a research project. Adequate provisions must also be made for soliciting the permission of each child's parents or guardians.

 

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.

 

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 Amercia; or

c.  has been 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.

 

Only in cases where a minor meets a, b, or c, can minors consent to research without parental permission.

 

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.   Only in the case of emergency care will a wavier be considered, see section 8.B.5.B.

 

Exemptions: The following are categories of research with children considered "exempt" from a formal Committee review.   This research, though considered exempt from formal review, does require IRB review to determine whether the rights and welfare of the children participating as subjects are adequately protected.  See additional information on “exempt” research, Section 7.C.

 

1. 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.

2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), 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.

3. 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.

4. Research involving the observation of public behavior is in the exempt category only if the investigator does not participate in the activities being observed.

             

OHRP has a new set of Frequently Asked Questions (FAQs) to help clarify issued related to reseach involving children.  You may access these FAQs from their website.

 

12. Investigational Drugs and Devices

 

Food and Drug Administration (FDA) regulations that govern the use of investigational drugs, devices, or biological products 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.

 

12.A.  Research Involving Investigational Drugs

 

12.A1.  Definition of an Investigational Drug from the FDA Regulations:

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 IND be filed 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”.

 

12.A.2.  Use of Approved Drugs for Off-Label Indications:

12.A.2.a.  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.

12.A.2.b.  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.

 

12.A.3.  Expanded Access of Investigational Drugs:

 

Investigational products are sometimes used for treatment of serious or life-threatening conditions either for a single subject or for a group of subjects. The procedures that have evolved for an investigational new drug (IND) used for these purposes reflect the recognition by the Food and Drug Administration (FDA) that, when no satisfactory alternative treatment exists, subjects are generally willing to accept greater risks from test articles that may treat life-threatening and debilitating illnesses. The following mechanisms expand access to promising therapeutic agents without compromising the protection afforded to human subjects or the thoroughness and scientific integrity of product development and marketing approval.

12.A.3.a.    Open Label Protocol or Open Protocol IND

These are usually uncontrolled studies, carried out to obtain additional safety data (Phase 3 studies). They are typically used when the controlled trial has ended and treatment is continued so that the subjects and the controls may continue to receive the benefits of the investigational drug until marketing approval is obtained. These studies require prospective Institutional Review Board (IRB) review and informed consent.

12.A.3.b.    Treatment IND

The treatment IND [21 CFR 312.34 and 312.35] is a mechanism for providing eligible subjects with investigational drugs for the treatment of serious and life-threatening illnesses for which there are no satisfactory alternative treatments. A treatment IND may be granted after sufficient data have been collected to show that the drug "may be effective" and does not have unreasonable risks. Because data related to safety and side effects are collected, treatment INDs also serve to expand the body of knowledge about the drug.

 

There are four requirements that must be met before a treatment IND can be issued: 1) the drug is intended to treat a serious or immediately life-threatening disease (defined as the stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment, e.g., advanced cases of AIDS, advanced congestive heart failure, advanced MS); 2) there is no satisfactory alternative treatment available in the intended patient population; 3) the drug is already under investigation, or trials have been completed; and 4) the trial sponsor is actively pursuing marketing approval.

 

Treatment IND studies require prospective IRB review and informed consent.

12.A.3.c.    Group C Treatment IND

The "Group C" treatment IND was established by agreement between FDA and the National Cancer Institute (NCI). The Group C program is a means for the distribution of investigational agents to oncologists for the treatment of cancer under protocols outside the controlled clinical trial. Group C drugs are generally Phase 3 study drugs that have shown evidence of relative and reproducible efficacy in a specific tumor type. They can generally be administered by properly trained physicians without the need for specialized supportive care facilities. Group C drugs are distributed only by the National Institutes of Health under NCI protocols. Although treatment is the primary objective and patients treated under Group C guidelines are not part of a clinical trial, safety and effectiveness data are collected.   Local IRB review and approval is required for these studies. 

12.A.3.d.    Parallel Track

The Agency's Parallel Track policy [57 FR 13250] permits wider access to promising new drugs for AIDS/HIV related diseases under a separate "expanded access" protocol that "parallels" the controlled clinical trials that are essential to establish the safety and effectiveness of new drugs. It provides an administrative system that expands the availability of drugs for treating AIDS/HIV. These studies require prospective IRB review and informed consent.

12.A.3.e.    Emergency Use IND

The need for an investigational drug may arise in an emergency situation that does not allow time for submission of an IND in the usual manner. If the intended subject does not meet the criteria of an existing study protocol, or if an approved study protocol does not exist, the usual procedure is to contact the manufacturer and determine if the drug or biologic can be made available for the emergency use under the company's IND. In such cases, FDA may authorize shipment of the drug for the specified use [21 CFR 312.36]. Such authorization is usually conditioned upon the sponsor filing an appropriate application as soon as practicable. Prospective IRB review is required unless the conditions for exemption are met [21 CFR 56.104(c) and 56.102(d)]. Informed consent is required unless the conditions for exception are met [21 CFR 50.23].

 

NOTE:  Data derived from an emergency use before IRB approval may not be used for research purposes (the use was for medical care, not research), but safety information should be reported to the FDA or the manufacturer as appropriate.

 

 

 

12.B.  Research Involving Medical Devices

 

12.B.1.  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. 

 

12.B.1.a.    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.  These regulations require, in part, that IRB approval be obtained and maintained throughout the investigation and that informed consent be obtained and documented.

 

12.B.1.b.    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.  As with non-significant risk devices, IRB approval is required prior to conducting clinical trials of the investigational device.

 

12.B.2.  IRB Review of Investigational Device Protocols

 

In addition to determining whether a study should be approved, the IRB will also determine whether the device presents significant or non-significant risk.

 

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.  In considering the risks of the device, the IRB will not simply judge the increase in risk over standard treatment, but rather the risk of the procedure as a whole.  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.

 

12.C.  Humanitarian Use Devices

 

 

 

13. Multi-Institutional Research Studies

 

13.A.  UVM/FAHC Researcher Collaborating with Another Institution

 

If an investigator is conducting a protocol in collaboration or cooperation with investigators at another institution s/he must inform the Committee of their participation in this project.  Please review the following flowchart to assist in determining what is required. 

 

If an appropriate review, i.e., review by a federally approved IRB, has been conducted and approval granted at the other institution, it may be possible to negotiate an agreement.  These provisions are required because when you collaborate, you accept some measure of responsibility for protecting the rights and welfare of the human subjects involved.  See the following chart for assistance in determining what additional steps may be required when collaborating with other institutions.

 

All projects conducted by UVM personnel, whether at another institution or at UVM, must be filed with the Committee. 

 

Multi-Institutional Research Studies FLOWCHART (next page)

 

 

Multi-Institutional Research Studies FLOWCHART

 

 

13.B.  UVM/FAHC Researcher as the Lead PI in a Multi-Institutional Study

 

A completed “Operations Center Activities Supplement” form must be submitted along with the protocol to the UVM/FAHC IRB for review.  In addition all participating sites must have a signed agreement, negotiated through UVM’s Pre-Award Services, prior to beginning activities. 

 

 

 Attachment A

 

University of Vermont

Committees on Human Research

 

A: Emergency Use of an Investigational Drug, Biologic, or Device                     Certification of Compliance Form

 

NOTE: THIS FORM MUST BE COMPLETED FOR EVERY APPLICABLE SUBJECT.  THE FORM MUST BE SUBMITTED WITHIN 5 WORKING DAYS AFTER THE USE OF THE TEST ARTICLE.

 

Date:

PI:

Name of Test Article

Date Test Article is to be (or was) used:

Check here if the proposed use meets the following definition from the FDA regulations:

"Emergency use means the 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)

Date and name of IRB Representative that you contacted:

Did you obtain consent?

Yes

No

If yes, describe verbal or attach signed consent form.