PROJECT SUMMARY/ABSTRACT More than 1 million U.S. youth sustain a concussion each year, and up to 30% experience persistent post- concussive symptoms (PPCS) such as headache, fatigue or difficulty focusing lasting one month or more. PPCS can interfere with normal adolescent development, resulting in issues with social and emotional dysfunction and even school failure. Despite these concerns, few evidence based treatments are available for youth with PPCS. We have conducted extensive work using a collaborative care (CC) framework integrating mental health care into a medical model, and we adapted this approach for youth with PPCS, combining concussion-focused cognitive behavioral therapy (cf-CBT), parenting skills training (PST) and care management (CM) to create wraparound treatment for youth with PPCS that could be delivered either in- person or virtually (using video conferencing software). We completed an R01 funded RCT with the CC approach, finding effectiveness for treating youth with PPCS, with improvements in concussive symptoms and quality of life at one year, and 60% of participants completing the intervention completely virtually. Of note, this intervention is unique in that two of the components are focused on parents or parents and youth together (PST, CM), and only one of the components (cf-CBT) is solely youth focused. We are now proposing to optimize and refine the CC approach, conducting a high efficiency MOST (multiphase optimization strategy) trial to assess the contribution of each of the three components (cf-CBT, PST and CM) to effectiveness of the intervention, thereby allowing us to streamline the intervention to only include active components. The analysis will be 23 factorial, with three intervention components and two levels of each (present or absent), resulting in 8 possible treatment combinations. The benefit of the MOST approach is that it combines all youth who receive a component, allowing us to assess all treatment components with only a modest sample size. We will recruit 368 youth with PPCS from two geographic locations (Seattle and Dallas), randomizing them to one of 8 treatment groups. Youth and/or parents will attend treatment sessions via video conferencing software over three months, and complete surveys regarding primary outcomes (concussive symptoms and health-related quality of life) and secondary outcomes (sleep, pain, mood and parental distress) at 3, 6 and 12 months. We will also assess potential mediators and moderators to allow for future tailoring and refinement. At the completion of this study, we will have a completely optimized and refined intervention for youth with PPCS ready for large scale implementation and dissemination.