Facilitating Scale-Up and Sustainment of High-Quality Lung Cancer Screening Using the QUILS System - Despite launching in 2015 as an evidence-based and policy-supported cancer screening strategy, lung cancer screening using low-dose computed tomography has suffered a broad range of implementation challenges that have constrained its beneficial impact on individual and population health outcomes. Lung cancer screening constitutes one of the most significant missed opportunities to reduce cancer mortality. While the literature has identified numerous implementation challenges that explain the starkly suboptimal uptake and constrained impact, few comprehensive solutions have been developed and tested to address this devastating translational gap between the potential generated by the National Lung Screening Trial (NLST) and the ongoing failure to achieve more than a small fraction of the possible mortality-reducing impact. The Kentucky LEADS Collaborative™ developed the QUILS™ System to facilitate implementation of lung cancer screening by packaging implementation strategies and evaluating the QUILS™ System in 10 lung cancer screening programs across Kentucky. Not only did the lung cancer screening programs demonstrate significant quality improvements, but Kentucky also achieved some of the highest rates of lung cancer screening implementation in the country. Additional preparatory research has helped refine the original QUILS™ System, and the proposed research seeks to evaluate the impact of the QUILS™ System 2.0 on the scale-up and sustainment of high-quality lung cancer screening in a sample of 60 lung cancer screening programs. The overarching aims are to facilitate high-quality lung cancer screening and to understand the factors that impact the scale-up and sustainment of high-quality lung cancer screening. In the UG3 Phase, the investigative team will (1) engage and prepare 60 lung cancer screening programs, (2) co-refine the proposed research methods, and (3) co-refine the QUILS™ System to prepare for the UH3 Phase trial. In a three-group pragmatic randomized comparative effectiveness trial (UH3 Phase), Aim 1 will compare implementation strategy components of the QUILS™ System on QUILS™ Index scores (a measure of program quality) and reach (as measured by the QUILS™ Index Reach Domain). Guided by PRISM and its RE-AIM outcomes, Aim 2 applies mixed methods to evaluate (a) moderators (i.e., contextual factors) and (b) mechanisms of each arm’s implementation strategies’ effects on reach, adoption, implementation (including adaptations), and maintenance/sustainment among 300 LCSP clinicians and staff. Aim 3 involves a thorough economic evaluation of the cost-effectiveness of the three different combinations of QUILS™ implementation strategy components. Aim 4 co-develops a QUILS™ Implementation, Tailoring, and Sustainment Guidebook to consolidate learnings and prepare for future dissemination. This innovative and comprehensive quality system offers the potential to accelerate implementation of lung cancer screening and simultaneously improve outcomes and public health.