PROJECT SUMMARY / ABSTRACT Opioid use has dramatically increased in the United States since 2000, and disproportionally affects individuals with co-occurring mental health disorders (COD). Individuals with COD are vulnerable to substance use relapses, mental health symptom exacerbations, opioid overdoses, suicide, homelessness, and criminal justice involvement. Although medication for opioid use disorder (MOUD) is the gold standard of care, engagement rates are as low as 18% which negatively impact outcomes. In addition, there is mixed evidence regarding the incremental therapeutic benefit of adding single behavioral interventions to improve MOUD outcomes, despite being recommended in clinical practice guidelines. Furthermore, while multi-component interventions exist, little is known about their incremental therapeutic effect on outcomes in conjunction with MOUD and standard medical management for those with a COD. Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking (MISSION) is one such multi-component, cross-disciplinary, team-based treatment approach, combining 3 evidence-based practices along with MOUD: 1) Dual Recovery Therapy (DRT), which is integrated group therapy for COD; 2) Peer Support (PS), offering support for people in recovery by people in recovery; and 3) Critical Time Intervention (CTI), a time-limited form of assertive community treatment. Although the effectiveness of MISSION is well established, given the difficulty with implementation uptake in large systems due to its complexity and the need to improve outcomes for those with a COD who receive MOUD, a critical next step is to understand the incremental therapeutic benefit of MISSION + MOUD, and identify highest value MISSION components that drive the largest clinical improvement and offer the greatest return on investment. In response to RFA-MH-21-145, the proposed 4-year study with a half fractional factorial design, “Supporting Treatment Access and Recovery for Co-occurring Opioid Use and Mental Health Disorders (STAR-COD),” will randomize 1,000 patients with COD across 9 MOUD programs to the following 5 conditions: 1) MOUD alone; 2) full MISSION protocol (CTI & DRT & PS) + MOUD; 3) CTI & DRT + MOUD; 4) PS & DRT + MOUD; or 5) CTI & PS + MOUD. There are four specific aims. Aim 1: To evaluate the effectiveness of MISSION or its components with MOUD versus MOUD alone, as well as the incremental benefits of MISSION or bundled parts + MOUD to improve engagement, substance use and mental health symptoms. Aim 2: To examine mechanisms of action of MISSION in COD. Aim 3: To conduct a comprehensive economic evaluation of MISSION or its parts and MOUD. Exploratory Aim: 4. To construct a predictive model to match optimum combined use of MISSION parts with patient needs to improve health outcomes. This proposal is aligned with NIMH’s strategic plan goal 4 “to increase the public health impact of services studies, investigators test ways to adapt,...