PROJECT SUMMARY – RP2 Smoking prevalence among Alaska Native and American Indian (ANAI) residents of Alaska is far greater than the national average and more than double that of White Alaskans (37% vs. 17%). The estimated health burden to the ANAI population nationally is staggering, with rates of smoking attributable deaths among ANAI people being 60% higher than for White people. Despite concerted efforts by tribal health organizations and the State of Alaska health department, current smoking cessation strategies have not reduced smoking prevalence among ANAI people in the last decade. We propose to refine and assess the acceptability and feasibility of a metabolism-informed smoking cessation intervention to improve tobacco cessation treatment for ANAI people. The goal of this project is to examine the acceptability and feasibility of using nicotine metabolite ratio to inform selection of pharmacologic treatment to increase smoking abstinence among ANAI people. In clinical practice, the choice of first-line treatment may depend largely on cost, side effect profile, physician familarity, pharmacy availability, and patient preference. Recently, a genetically informed biomarker, nicotine metabolite ratio, has shown promise to select optimal pharmacologic treatment among non-ANAI populations who desire to quit smoking. This study found that patients with slow nicotine metabolism had similar response to varenicline and NRT, while those with normal metabolism responded better to varenicline. No prior work has piloted implementation of using metabolic markers for treatment selection among ANAI people. We will use a community-based participatory research (CBPR) approach to refine a metabolism-informed care model described by Wells et al. that has nurse tobacco specialists provide a medication recommendation. We will then beta-test the refined intervention in clinic, make additional refinements, and assess the refined intervention in a single-arm pilot trial with 40 ANAI participants. We will identify factors that impede or facilitate implementation of the refined intervention in the Alaska Native tribal health system using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and CFIR (Consolidated Framework of Implementation Research) implementation frameworks. The Specific Aims are to: 1) Refine and beta-test a metabolism-informed pharmacologic intervention to optimize design and participation, 2) Conduct a single-arm pilot trial assessing the acceptability and feasibility of the refined intervention, and 3) Examine factors which impede or facilitate implementation of the intervention within the Alaska Native tribal health system. The proposed project will contribute important knowledge to the scant literature on effective tobacco cessation interventions among ANAI people in real-world settings. These activities will also build a solid foundation for a larger, pragmatic trial, with potential applicabili...