Project Summary/Abstract The misuse of opioids has reached an epidemic level in the United States, with approximately 2 million people suffering from opioid use disorder and over 46,800 opioid overdose fatalities in 2019. Medication-based treatment for opioid use disorder—such as buprenorphine maintenance—is effective and can save lives, however, approximately half of people who receive buprenorphine do not adequately respond or drop out of treatment. In contrast to other substance use disorders, the addition of behavior therapy to buprenorphine has not consistently shown improvements in opioid use outcomes for opioid use disorder. Preliminary evidence suggests that not everyone may need the addition of behavior therapy to buprenorphine to reduce opioid use, but that certain subgroups of people may benefit from behavior therapy. The ability to understand heterogeneity in response to treatment for opioid use disorder is hampered by the need for very large sample sizes to test questions about moderators of treatment response. Understanding subgroup differences can ultimately inform personalized medicine approaches to the treatment of opioid use disorder. Our objective for this proposal is to answer urgent questions about subgroup responses to behavioral therapy by harmonizing data from 4 completed clinical trials of treatment for opioid use disorder. These NIDA-funded randomized trials each tested the efficacy of behavior therapy added to buprenorphine maintenance for opioid use disorder and include common data elements, allowing for their harmonization. Our project aims include: (1) to identify subgroups who respond to behavior therapy when added to buprenorphine maintenance for opioid use disorder, (2) to quantify the efficacy of behavior therapy for improving buprenorphine treatment retention, and (3) to quantify the efficacy of behavior therapy for functional outcomes. The results from this study will provide important information about who responds to behavior therapy and the effect of behavior therapy on non-opioid use endpoints. Our proposal will utilize well-validated longitudinal data analysis methods, including a rigorous approach to missing data. By using existing datasets, this proposal provides an efficient way to answer urgent questions about the treatment of opioid use disorder and provides significant added value to these trials. These findings can be immediately used to inform personalized approaches to treatment for opioid use disorder and will also contribute to understanding of the impact of behavior therapy on endpoints of interest to patients and families.