Even after significant reductions in long-term opioid therapy (LTOT) prescribing for chronic pain nationally, approximately 13 million US adults receive LTOT, putting them at risk for an array of harms often without adequate benefit. Due to the often unfavorable risk-benefit profile of LTOT, current consensus guidelines promote 1) continuous re-assessment of risk and benefit of LTOT and 2) reduction or discontinuation of LTOT while supporting pain self-management strategies and non-opioid pain care when benefit no longer outweighs harm. However, the guidelines lack crucial details--such as how to assess risk vs. benefit--hampering quality improvement efforts. Clinical research has been slowed by lack of consensus related to important questions such as: what is the threshold for determining that harm outweighs benefit in LTOT?, Should there be a new diagnostic entity to characterize the clinical scenario of harm outweighing benefit?, and, if so, What are its distinguishing characteristics? These research and clinical gaps translate into potentially poor quality pain care for patients on LTOT, including low efficacy and heightened risk in a vulnerable population. In accordance with RFA-DA-23-042, we propose the establishment of the Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy – Yale Resource Center (MIRHIQL-YRC) to address the national opioid public health crisis via a focus on the oft-overlooked population of patients on LTOT for whom risk may outweigh benefit but who do not have opioid use disorder. We propose an integrated, multi- level structure of the MIRHIQL-YRC modeled after our high-functioning IMPOWR-YOU Research Center, with a Community Steering Committee (CSC) at the hub and several smaller, agile workgroups focusing on specific tasks but moving forward in a highly inter-related fashion. The CSC's impact will be bolstered by the presence of partners historically left out of consensus-building projects: persons with lived experience and frontline clinicians, groups for whom it is crucial the tools and other products developed are patient-centered, non- stigmatizing, feasible and practical. Via this structure, the MIRHIQL-YRC, governed by the CSC, will pursue four objectives: (1) Facilitating, through a variety of mechanisms detailed herein, the successful execution of the companion MIRHIQL network R01 clinical trials; (2) Creating a risk-benefit decision tool to assist providers in determining when opioids should be continued as prescribed, tapered, or tapered and discontinued; (3) Creating a clinical definition, identifying associated symptoms/behaviors, and generating a screening assessment for individuals on LTOT for whom harms outweigh the benefits; and (4) Validating the clinical definition, associated symptoms/behaviors, and screening assessment in an independent prospective cohort study. Our multi-disciplinary team with a long track record of successful collaboration a...