Alison B. Breland, Ph.D. - US grants

DESCRIPTION (provided by applicant): Assessing new, potential reduced exposure products (PREPs) for smokers is essential to predict if they will increase, decrease, or fail to change the health risks of smoking. In the past, some harm reduction efforts (i.e., low-yield cigarettes) did little to reduce smoking's lethality. Smokers using these cigarettes compensated for lower yields of nicotine by taking larger, longer, or more frequent puffs, thus potentially increasing exposure to harmful smoke constituents. In addition, some research indicates that men and women differ in their response to nicotine/tobacco; thus it is important to understand differential responses to these products. To assess the effects of PREP use, male and female smokers will participate in a 4-week, within-subjects study. Each week, participants will use either one of two PREPs, their own brand, or will abstain from smoking. Smokers will use these products outside of the laboratory but will be also be assessed for behavioral changes in the laboratory. Subjective and physiological withdrawal suppression, as well as smoke constituent exposure (CO, nicotine, nitrosamines) will be measured. Measuring these factors is essential to determine if these PREPs reduce the risk associated with smoking, and to avoid past failures to evaluate products which claimed to decrease exposure to harmful smoke constituents.

Project Summary. FDA?s tobacco regulatory authority calls for an evidence-based approach that emphasizes protecting public health. This approach differs from pharmaceutical regulation and thus requires differently trained regulatory scientists. The Career Enhancement Core (CEC) continues and expands the Center for the Study of Tobacco Products? (CSTP?s) program of tobacco regulatory science and research training designed to meet FDA and NIH needs. The CEC offers an updated graduate course on tobacco regulatory science, educates pre- and post-doctoral appointees, engages investigators new to tobacco regulation, and, at no added cost to NIH, integrates tobacco regulatory science into two existing international programs that train scientists and policymakers. The specific aims of the CSTP?s CEC are to: (1) conduct a transdisciplinary graduate course and produce methods-based webinars, (2) educate pre-doctoral and post-doctoral appointees, (3) engage non-CSTP faculty in tobacco regulatory science, (4) create a pilot research program, and (5) integrate tobacco regulatory science into ongoing international training programs. In sum, the CSTP proposes a Career Enhancement Core that will continue to teach tobacco regulatory science and transdisciplinary methods for tobacco product evaluation, support pre-doctoral and post-doctoral appointees, and engage new investigators in tobacco regulatory science. The pilot research program will help appointees learn proposal writing and management skills while fostering collaborations between CSTP faculty and investigators new to tobacco regulatory science. Taken together, all of these activities support the U54- funded CSTP and will build on the CSTP?s history of producing an experienced cadre of tobacco regulatory scientists ready for productive careers in academia, government, and other areas.

Project Summary. The Center for the Study of Tobacco Products (CSTP) has developed a model for evaluating novel tobacco products using, as exemplars, electronic cigarettes (ECIGs) that heat a liquid that often contains nicotine, forming an aerosol that users inhale. Now, CSTP leverages its methodological and ECIG expertise to pivot from product evaluation to an integrative theme of impact analysis. FDA tobacco regulation must protect public health, though regulations may also have unintended consequences that cause harm. For example, limiting ECIG liquid nicotine content, as in the European Union, can drive use of higher power ECIGs that aerosolize more liquid, leading users to inhale more nicotine and other toxicants. Other potential ECIG regulations involve constraining amount of nicotine emitted/unit time (nicotine ?flux?) that may influence product toxicity and abuse liability, or reducing flavor availability that may lead users to mix their own flavored liquids. If FDA could predict a potential regulation?s effects, then refinements before the regulation is issued might maximize its health-promoting effects and minimize unintended consequences. Methods exist for assessing a regulation?s effects once it is in place, but few data-driven models predict impact beforehand. Any such model must draw from several domains to assess how a potential regulation might change product toxicity, user behavior, and addiction/abuse liability. Also, the model must demonstrate the extent to which predictions about potential regulatory effects describe actual population-level outcomes. CSTP addresses this issue with this application: Projects 1-3 will test hypotheses and generate predictions regarding the impact of three potential ECIG regulations (i.e., limit nicotine, constrain flux, reduce flavor availability); Project 4 will test these predictions at the population level. CSTP?s vision is to provide tools to guide regulation development so that, by the time a regulation goes into effect, validated methods have tested it, refined it, and generated data showing that its health-promoting effects are maximized and unintended consequences minimized. The team (Drs. Eissenberg, Breland, Shihadeh, Cobb, Barnes, Cohen, Fagan) will complete 4 integrated projects that aim to: predict product toxicity, predict user behavior, predict abuse liability, and assess potential regulation impact. A Contextual Knowledge Core uses mixed methods to ensure Projects 1-4 reflect the real world. A Career Enhancement Core conducts a tobacco regulatory science course, supports pre- and post- doctoral appointees, and pilot projects. An Administrative Core supports financial/managerial processes, biostatistical needs, receives input from an External Advisory Board, and interfaces with FDA, NIH, and others. Overall, CSTP?s integrative theme of impact analysis draws on the team?s expertise in tobacco product toxicity, user behavior, and abuse liability. We seek to provide FDA with hypothesis-driven data regarding advanced generation ECIGs and test predictions about some potential regulations now, while developing a model that can be used to shape, refine, and predict the effects of many potential regulatory actions in the future.

Project Summary. The Center for the Study of Tobacco Products (CSTP) has developed a model for evaluating novel tobacco products using, as exemplars, electronic cigarettes (ECIGs) that heat a liquid that often contains nicotine, forming an aerosol that users inhale. Now, CSTP leverages its methodological and ECIG expertise to pivot from product evaluation to an integrative theme of impact analysis. Specifically, the CSTP proposes methods with which FDA can generate predictions regarding a potential regulation?s effects, and then whether or not the predicted effects occur in the population can be tested. The CSTP?s model assesses how potential regulation might influence product toxicity (Project 1), user behavior (Project 2), and product addiction/abuse liability (Project 3). In this context, Project 2 will generate new data regarding the effects of advanced-generation ECIGs on user behavior and will contribute, along with Projects 1 and 3, to population-level predictions: Project 4 will test those population-level predictions. FDA regulations are intended to promote health, but also may have harmful unintended consequences. For example, limiting liquid nicotine to <20 mg/ml, as in the European Union (EU), could drive use of high power ECIGs that deliver more nicotine and other toxicants. Unintended consequences may also occur from other actions, like constraining ECIG nicotine flux (amount of emitted nicotine/unit time), or reducing flavor availability. The consequences of these and other potential regulatory actions may be predicted using results from clinical lab studies in which variables relevant to regulation are manipulated systematically and subjective effects, puff topography (e.g., puff duration, volume), liquid consumption, and nicotine delivery are measured. Results can inform testable population-level predictions regarding device/liquid preferences, amount of liquid consumed, dual ECIG/tobacco cigarette use, and dependence. Thus, Project 2 specific aims are to use established clinical lab methods to examine, in independent studies each involving 68 exclusive ECIG users and 68 non-ECIG using smokers, the extent to which subjective effects, puff topography, liquid consumption, and nicotine delivery are influenced by three potential regulatory actions: (1) limits on nicotine, (2) constraints on nicotine flux, and (3) reduction in flavor availability. Project 2 is informed by the Contextual Knowledge Core that ensures that independent variables reflect real-world conditions. Results will provide new data regarding the role of nicotine concentration, flux, and flavor availability on ECIG user behavior, while informing population-level predictions. Project 4 examines these predictions at the population level. Thus, this project is part of a center with an integrative theme of impact analysis that draws from the team?s clinical lab expertise to provide FDA tools that can be used to guide regulation development so that, by the time a regulation goes into effect, methods predictive of population-level phenomena have tested it, refined it, and generated data that show that its health-promoting effects are maximized and unintended consequences are minimized.

Project Summary. The Center for the Study of Tobacco Products (CSTP) has developed a model for evaluating novel tobacco products using, as exemplars, electronic cigarettes (ECIGs) that heat a liquid that often contains nicotine, forming an aerosol that users inhale. Now, CSTP leverages its methodological and ECIG expertise to pivot from product evaluation to an integrative theme of impact analysis. FDA tobacco regulation must protect public health, though regulations may also have unintended consequences that cause harm. For example, limiting ECIG liquid nicotine content, as in the European Union, can drive use of higher power ECIGs that aerosolize more liquid, leading users to inhale more nicotine and other toxicants. Other potential ECIG regulations involve constraining amount of nicotine emitted/unit time (nicotine ?flux?) that may influence product toxicity and abuse liability, or reducing flavor availability that may lead users to mix their own flavored liquids. If FDA could predict a potential regulation?s effects, then refinements before the regulation is issued might maximize its health-promoting effects and minimize unintended consequences. Methods exist for assessing a regulation?s effects once it is in place, but few data-driven models predict impact beforehand. Any such model must draw from several domains to assess how a potential regulation might change product toxicity, user behavior, and addiction/abuse liability. Also, the model must demonstrate the extent to which predictions about potential regulatory effects describe actual population-level outcomes. CSTP addresses this issue with this application: Projects 1-3 will test hypotheses and generate predictions regarding the impact of three potential ECIG regulations (i.e., limit nicotine, constrain flux, reduce flavor availability); Project 4 will test these predictions at the population level. CSTP?s vision is to provide tools to guide regulation development so that, by the time a regulation goes into effect, validated methods have tested it, refined it, and generated data showing that its health-promoting effects are maximized and unintended consequences minimized. The team (Drs. Eissenberg, Breland, Shihadeh, Cobb, Barnes, Cohen, Fagan) will complete 4 integrated projects that aim to: predict product toxicity, predict user behavior, predict abuse liability, and assess potential regulation impact. A Contextual Knowledge Core uses mixed methods to ensure Projects 1-4 reflect the real world. A Career Enhancement Core conducts a tobacco regulatory science course, supports pre- and post- doctoral appointees, and pilot projects. An Administrative Core supports financial/managerial processes, biostatistical needs, receives input from an External Advisory Board, and interfaces with FDA, NIH, and others. Overall, CSTP?s integrative theme of impact analysis draws on the team?s expertise in tobacco product toxicity, user behavior, and abuse liability. We seek to provide FDA with hypothesis-driven data regarding advanced generation ECIGs and test predictions about some potential regulations now, while developing a model that can be used to shape, refine, and predict the effects of many potential regulatory actions in the future.