Project Summary A primary aim of the proposed Program Project is to develop an optimized healthcare system smoking program (the Comprehensive Chronic Care Smoking Treatment Program: CCCSTOP). This will be accomplished using the Multiphase Optimization Strategy (MOST), an engineering-inspired methodological framework for developing, optimizing, and evaluating multicomponent treatments. The Design and Optimization Core serves the Program Project by providing a centralized resource for expertise and support pertaining to this innovative approach. The Specific Aims will be: 1) To support and serve as an intellectual resource for the application of MOST to develop, optimize, and evaluate CCCSTOP. To conduct the research proposed in this Program Project application, it will be necessary to integrate data and substantive knowledge about smoking cessation with methodological expertise on topics such as efficient experimental design and statistical analysis. It will also be necessary to engage in complex decision-making based on the results of experimentation. This core will promote, support, and coordinate these efforts, working closely with the Data Analysis Core. 2) In concert with other project investigators, to refine and further develop the MOST framework and related methodological tools to enhance the work of this Program Project. One area of refinement is the application of ideas and procedures from decision analysis, to expand the application of MOST to more realistic—but also more complex—situations in which multiple outcomes are considered in the identification of an optimized treatment strategy (e.g., by using multiple criteria decision analysis). This procedure will be implemented in this project, and will serve as a resource for others who are optimizing interventions in cancer prevention and treatment where interventions target more than one outcome. 3) To disseminate the MOST approach and related methodological tools to the cancer control research community. The refined decision- making procedure and related methodological tools will be disseminated via journal articles, talks, workshops, and training activities to scientists and clinicians not only in the smoking cessation area but also in other areas of cancer prevention and treatment.