The evidence-based use of prescription medications has led to substantial improvement in healthy aging. Despite this, the use of medications by patients and providers remains suboptimal. Many patients are not prescribed guideline-recommended therapies from which they would benefit; among those for whom appropriate treatment is initiated, almost half do not adhere over the long-term; and others receive potentially- hazardous medications with an unfavorable balance of risks and benefits. The result: preventable adverse health outcomes and health spending for middle-aged and older adults. While many factors influence the suboptimal use of prescription medications, individual, interpersonal and institutional behaviors are central. As a result, existing intervention to address these issues have attempted to remind, reward, motivate, simplify or otherwise change behavior. Unfortunately, these approaches have only been modestly effective and even among those do work, behavior change is rarely sustained over the long- term. The results can be explained by the lack of integrating behavioral principles when designing interventions, a limited focus on evaluating how to deliver them over the long term, and the inherent challenges in delivering precise and personalized behavior change at population scale. Thus, the Brigham and Women’s Hospital Roybal Center for Therapeutic Optimization using Behavioral Science will continue to focus on the thematic area of promoting adherence and maintenance of long-term behavior change. The structure and activities of the proposed Center will be based upon 4 key principles: (1) a multi-disciplinary approach; (2) the testing of principle-driven interventions in real-world settings; (3) the explicit testing of mechanisms of action, and (4) the use of novel analytic methods and technological approaches to gain a deeper understanding of behavioral mechanisms and to personalize interventions. Based on these principles, our Center will have the following Specific Aims:(1) to oversee a translational research program for the testing of principle-driven, potent, practical, scalable and sustainable behavioral interventions to enhance the appropriate prescribing and use of evidence-based medications.; (2) to strategically direct and to provide scientific oversight, fiscal and operational support to ensure the successful completion of behavioral interventions funded by the Center.; and (3) to conduct trials evaluating principle-drive interventions that aim to sustain behavior change for the use of evidence-based medications. The proposed Year 1 studies conducted in partnership with large delivery systems and testing novel approaches to promote the deprescribing of high- risk medications and to support adherence to evidence-based preventive therapies. The expected impact of the Roybal Center for Therapeutic Optimization using Behavioral Science is that it will develop principle-driven interventions that will readily translate to impro...