PROJECT SUMMARY Combustible cigarette smoking is the leading cause of preventable death and disease in the US. Each year, more than 400,000 Americans die due to reasons related to tobacco use. Strong scientific evidence exists linking smoking to elevated risk of pulmonary diseases, cardiovascular diseases (e.g. heart attack, heart failure, and stroke), and multiple types of cancer (e.g. of the oral cavity, lung, esophagus, kidney, uterus, and bone marrow). To curb these high rates of mortality and morbidity and protect the American people, the 2009 Family Smoking Prevention and Tobacco Control Act granted the Food and Drug Administration (FDA) the authority to regulate the manufacture, distribution, and marketing of all products that meet the statutory definition of tobacco products, defined as any product made or derived from tobacco and intended for human consumption. To inform science-based tobacco regulations, current rigorous research is necessary on the factors associated with toxicant exposure and successful quitting since past work is less applicable to today’s continually evolving tobacco market and use patterns. Tobacco use patterns now include a variety of flavored combustible (e.g., little cigars) and non-combustible tobacco products (e.g. ECIGs) that may be used concurrently (dual-/poly-product use). These patterns may produce different profiles of toxicant exposure (thus influencing health outcomes), and different levels of nicotine dependence (thus influencing cessation rates). This response to RFA-OD-19-022 uses state-of-the-art statistical techniques to analyze national longitudinal data from five waves of the Population Assessment of Tobacco and Health (PATH) Study, to identify classes of smokers in terms of their toxicant exposure and to understand trends in overtime patterns of nicotine dependence and tobacco use and their relationship with successful quitting. The two specific aims are to: 1) Conduct cluster analysis on tobacco biomarkers of adult current cigarette smokers and group smokers into clusters based on concentrations of tobacco toxicant biomarkers (i.e., urinary biomarkers of exposure to nicotine, TSNAs, PAHs, and VOCs) collected at Wave 3 of the PATH study. We will examine whether use patterns (e.g. flavor, exclusive, dual, and poly use), personal characteristics, and nicotine dependence vary by cluster membership. 2) Perform growth curve analysis to model change over time in nicotine dependence to identify and describe dependence trajectories (i.e. differential nicotine dependence patterns) during four consecutive waves and examine the relationship between these trajectories, overtime change in tobacco use patterns, and successful quitting (3+ m abstinence). In sum, this project addresses priority research questions and is directly relevant to the mission of the FDA’s CTP. Resultant data could be leveraged to inform product labeling and public health campaigns, especially those addressing toxicant exposure and dependence risk of dual/poly product use. Until consumers are fully informed about the risks they take when engaging in dual/poly tobacco product use, we can expect more and more of them to engage in this potentially hazardous behavior.

PROJECT NARRATIVE Since cigarette smoking is the leading cause of preventable death and disease in the US, understanding determinants of smoking toxicant exposure and successful quitting in the context of today’s evolving tobacco environment is highly relevant to public health. The project will utilize innovative analysis of nationally representative data to inform regulations of tobacco products appropriate to reduce tobacco-related mortality and morbidity. Resultant data could be leveraged to inform the evaluation of new product standards and the development of new health labels and public information campaigns to raise awareness of health hazards associated with different tobacco types and use patterns.