PROJECT SUMMARY/ABSTRACT Four key federal-level tobacco control actions were taken in the US in December 2019/January 2020 to reduce Electronic Nicotine Delivery System (ENDS)/tobacco use appeal and access, particularly among young people. These 4 actions were: (1) ENDS Flavors/Device Guidance, in which FDA prioritized enforcement against “any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored ENDS product),” (2) ENDS Marketing Guidance, in which FDA prioritized enforcement against “any ENDS product that is targeted to minors or whose marketing is likely to promote use of ENDS by minors,” (3) ENDS Access Guidance, in which FDA prioritized enforcement against “all other ENDS products for which the manufacturer has failed to take (or is failing to take) adequate measures to prevent minors’ access,” and (4) Federal T21, in which the federal minimum age of sale of tobacco products was raised from 18 to 21 years. Around the same time, though, two national public health events occurred that likely also contributed to population-level changes in ENDS/tobacco use behaviors: an outbreak of ENDS-associated lung injuries was identified by CDC in August 2019 (EVALI), and the spread of a novel coronavirus was declared a public health emergency in the US in January 2020 (COVID19). The shared historical timing of these actions and events require innovative methods to address the challenge of assessing the specific impacts of each federal action. We will use a theoretically grounded mediational model to disentangle overall impacts into action-specific impacts via intermediate measures of appeal and access expected to change in response to each federal action, based on the IARC Handbook: Methods for Evaluating Tobacco Control Policies. We will conduct secondary data analyses using two complementary nationally-representative data sources, which each assess key intermediate measures of appeal and access, and together include over 61,000 participants, to investigate the impacts of ENDS Flavors/Device Guidance, ENDS Marketing Guidance, ENDS Access Guidance, and Federal T21 on ENDS/tobacco use behaviors in the US, while also considering simultaneous impacts of EVALI and COVID19. We will use the longitudinal Population Assessment of Tobacco and Health (PATH) Study youth and adult surveys (2017-2021) and the US arm of the International Tobacco Control (ITC) Project youth and adult surveys (2018-2021), leveraging the fully uninterrupted data collection and early fielding of COVID19 items unique to ITC, as well as state identifier data (PATH and ITC) to account for state-level Tobacco 21 policies in effect prior to Federal T21. We will use mediation analyses to statistically decompose the total effects of actions into the hypothesized mediator effects. Examining all 4 federal actions using a theory-driven conceptual model will provide a comprehensive understanding of the impacts of each action on the ENDS/tobacco use behaviors of millions o...