PROJECT 1 Abstract Under the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration (FDA) is required to show that any new rule to regulate the marketing, sale or content of tobacco products is “appropriate for the protection of the public health.” To provide the FDA with a framework to assess the potential health impacts of tobacco regulations, Project 1 will harmonize and extend well-established Center for the Assessment of Tobacco Regulations (CAsToR) tobacco control simulation models to examine the impact of FDA regulatory actions on future trends in cigarette, cigar, electronic nicotine delivery systems (ENDS), and other novel tobacco product (ONPs) use and associated health outcomes. This project will focus on Behavior (Aim 1), Impact Analysis (Aims 2 and 3) and Health Effects (Aims 2 and 3) as Scientific Domains (RFA-OD-22- 04). Project 1 has three aims. Aim 1. Characterize longitudinal patterns of use and transitions of cigarettes, cigars, and ENDS, individually and in combination. Oral nicotine, heated tobacco products (HTPs), and ONPs will be considered as data on their use become available. Using nationally representative health surveys, literature reviews and transitions estimates, we will extend a previously developed framework to examine transitions between regular cigarette and ENDS use to include cigars, HTPs and ONPs. We will develop transition parameters to distinguish between exclusive, former, dual use and switching patterns for each product. Aim 2. Develop simulation models of the use patterns of cigarettes, cigars, ENDS, and other tobacco products in the US and their health implications. We will expand the CAsToR simulation models (i.e., SimSmoke, Mendez and Warner, Microsimulation and SAVM) to incorporate product use, health outcomes and all-cause mortality risk of cigars, HTPs, and ONPs. Population transitions in the models will be modeled through sex- and age-specific initiation and cessation rates for each product and switching rates between products. Each model will be calibrated and validated against prevalence rates by age and sex from surveys for each product type. Aim 3. Model the impact of existing and potential regulations on tobacco use patterns and all-cause mortality associated with cigarette, cigar, ENDS, and other novel tobacco product use. For all models, we will create the capability to examine how past and future FDA policies will impact combustible and novel nicotine product use and associated health outcomes. We will develop best estimates and credible ranges of the policy effect on each product’s initiation, cessation, and switching rates. We will consider variations in policy effect sizes by age, sex, race, and socioeconomic status. We will initially focus on the relationship between cigarette and ENDS use, and then incorporate cigar use. Comparative analyses of the four models’ predictions will be conducted to refine the likely best-case, worst-case, and most likely projec...