The overarching goal of this application for a Phase 2 COBRE award is to further develop the VCBH.

The overarching scientific priorities of the VCBH are:

• increasing scientific understanding of the mechanisms underpinning vulnerability to these unhealthy behavior patterns, including the contribution of biases in decision making and socioeconomic disadvantage, and
• developing and evaluating the efficacy and cost-effectiveness of behavior-change interventions to promote health.

Advances in each of those areas are essential to improving U.S. population health, reducing health disparities, and curbing spiraling health care costs. The VCBH made considerable progress during Phase 1 towards establishing a vibrant, multidisciplinary center of research excellence that is already having local, national, and international impact. Phase 2 funding will allow the VCBH to further establish and develop a productive, sustainable presence in this important area of biomedical research.

Aim 1: Recruit and organize the multidisciplinary senior and early-career faculty and advisors necessary to lead and sustain the VCBH mission.

Aim 2: Provide promising early-career faculty with the research opportunities, mentoring, and career development support necessary to establish themselves as successful, independent investigators.

Aim 3: Establish an Administrative Core that effectively leads and coordinates a multidisciplinary research center of excellence, trains the next generation of scholars, and obtains the external funding necessary to sustain the VCBH beyond COBRE support.

Aim 4: Establish a research core that supports the efforts of investigators in the VCBH and beyond to study behavior and health relationships pertinent to the VCBH mission. The Behavioral Economics and Intervention Sciences Core (Core B) consists of the following three modules of expertise:

(a) A Decision-Making component that supports research strategies and instruments to examine individual differences in biases and deficiencies in decision-making (e.g., temporal discounting, other executive functions) using conventional paper-and-pencil and laptop assessment platforms, as well as those that leverage functional magnetic resonance imaging (fMRI) testing.

(b) An Intervention Sciences component that (i) assists with development and evaluation of behavior change interventions, and (ii) supports the integration of emerging technologies with those interventions;

(c) An Economic Modeling component that assists with developing and implementing cost-effectiveness analyses for the intervention studies.

Aim 5: Establish a Collaboration, Dissemination, and Education Core (Core C) that facilitates local, state, national, and international impact and educates the next generation of scholars in Behavior and Health by:

(a) Nurturing and coordinating bi-directional collaborative relationships with (i) Vermont leaders in health care policy and delivery, (ii) a network of universities and research institutes located in other IDeA states (Brown University, University of Kentucky, Dartmouth, University of Nebraska, Laureate Institute for Brain Research), non-IDEA states (Johns Hopkins University, State University of New York at Buffalo, Wayne State University), and internationally (University of Glasgow, Glasgow, Scotland; Oviedo University, Oviedo, Spain; Makerere University, Kampala, Uganda) where there is strong interest and expertise in the area of behavior and health;

(b) Disseminating new knowledge on behavior and health through the annual VCBH national conference and annual Special Issues of the peer-reviewed journal Preventive Medicine;

(c) Educating the next generation of scholars in the area of behavior and health through the VCBH monthly lecture series, seminars, and workshops offered at UVM and also streamed live to collaborators and interested others.

VCBH is the home of the UVM Tobacco Center of Regulatory Science (TCORS), one of nine such centers in the U.S. that are supported through a cooperative agreement of the National Institutes of Health (NIH) and Food and Drug Administration (FDA). The Family Smoking Prevention and Tobacco Control Act has given the federal government (i.e., FDA) the authority to bring science-based regulation to the manufacturing, marketing, and distribution of tobacco products. UVM and the other TCORS centers will provide scientific expertise relevant to the FDA’s regulatory mission. 

VCBH addresses one of the crosscutting and two of the specific research priorities of the FDA Center for Tobacco Products in carrying out its charge of regulating tobacco products. We approach these priorities using the concepts, principles, and methods of behavioral economics and behavioral pharmacology. We work closely with collaborators and consultants from Brown University, Johns Hopkins University, University of Minnesota, and University of Pittsburgh. 

We will continue our crosscutting integrative theme of vulnerable populations focusing on two FDA Center for Tobacco Products scientific domains: addiction and behavior. More specifically, we plan to expand our center's research on nicotine standards for cigarettes and addiction risk in populations already at an increased risk for:

• cigarette smoking,
• addiction, and
• smoking-related adverse health outcomes, including socioeconomically disadvantaged populations, individuals with other substance use disorders, and individuals with mental illness.

We will extend our research applying the principles and methods of behavioral economics, behavioral pharmacology, and neuroimaging to examine the effects of reducing the nicotine content of cigarettes on cigarette smoking in vulnerable populations with and without substitute non-combusted nicotine products readily available. We will also examine whether flavors enhance appeal of the non-combusted alternative. 

Primary Aims

Aim 1: Continue our Administrative Core to provide the administrative and fiscal oversight and infrastructure necessary to successfully complete the proposed and FDA CTP initiated research projects, and support this vibrant multidisciplinary center of research and mentoring excellence in tobacco regulatory science. 

Aim 2: Complete three multi-site clinical trials evaluating the effects of very low nicotine content (VLNC) cigarettes on smoking rate, dependence severity, neurobiological impacts, and toxin exposure using between subject, parallel group, research designs. Participants in each trial will be randomly assigned to 16 weeks of exposure to (1) normal nicotine content cigarettes (NNC) alone, which will serve as the control condition, (2) VLNC cigarettes alone, (3) VLNC’s + tobacco flavored nicotinized e-cigarettes (TF e-cigs), or (4) VLNC’s + nicotinized e-cigarette + preferred e-cigarette flavorings (PF e-cigs). We chose this design to be of potential direct practical utility to the FDA CTP by modeling possible market scenarios in which a reduced nicotine content policy may be implemented.

Aim 3: Conduct a two parallel groups, 12-week multi-site, randomized clinical trial in which pregnant women will be assigned to continue smoking their usual brand or to use a VLNC cigarette. We will assess smoking rate, dependence severity, toxin exposure, and pregnancy-specific measures. Use of noncombustibles will be recorded as a dependent variable but will not be examined as an independent variable. 

Aim 4: Conduct pilot studies and rapid-response projects related to vulnerable populations in coordination with FDA CTP. Through our main research projects, pilot studies, and participation in TCORS workgroups during the current funding period, the UVM TCORS has developed a strong infrastructure and toolkit to be maximally responsive to FDA’s priority research areas. We will collaborate closely with FDA CTP.

Aim 5: Continue our Career Enhancement Core mentoring early career investigators (predoctoral and postdoctoral mentees) in tobacco regulatory science. The program will continue to be primarily located at UVM, but also include postdoctoral mentoring at our collaborating institutions, Brown University, and Johns Hopkins University. At each institution, the career enhancement program will continue to be integrated with their respective longstanding and highly regarded T32 training programs in addictions research.