Data-Driven Approaches for Opioid Use Disorder Treatment, Recovery, and Overdose Prevention in Rural Communities via Mobile Health Clinics and Peer Support Services - Over 100,000 lives were lost due to drug overdose in the past year, of which 80% involved opioids. Despite the effectiveness of medications for opioid use disorder (MOUD) at reducing opioid misuse and risk of overdose, only 10% of people in need receive treatment. Moreover, treatment retention is low (30-50%) with half of patients experiencing an opioid use recurrence. Peer support specialists (PSSs), who are individuals with direct experience with and successful recovery from Substance Use Disorder, can offer social support and directly address treatment and recovery barriers for individuals with Opioid Use Disorder (OUD). Our systematic review showed that OUD patients receiving a PSS intervention were more likely to initiate MOUD, but evidence of effectiveness for MOUD retention or opioid use remain inconclusive. Low treatment initiation and retention rates for OUD are especially concerning for rural populations and underserved communities, who rarely have access to clinicians who can prescribe MOUD and experience substantial barriers to care, including limited social support, lack of insurance, homelessness, transportation issues, and stigma. Given that these populations are also at an elevated risk of opioid overdose due to many of these same factors, interventions to increase OUD treatment, retention, and overdose prevention in rural and medically underserved communities are urgently needed. Mobile health clinics (MHC) are an effective and versatile tool for timely delivery of interventions, including those for OUD treatment, to medically underserved and at-risk communities. However, effective intervention delivery for OUD treatment initiation, retention, and overdose prevention have not been explored in MHC settings. The goal of our proposal is to increase MOUD treatment initiation, treatment retention, and prevent overdose deaths in medically underserved communities (via MHC) through development, testing, delivery, and evaluation of an innovative 1) PSS intervention to increase MOUD initiation and retention rates in rural and underserved populations and 2) modeling framework to prioritize at-risk communities for MHC delivery (based on overdose deaths prevented). Research has shown that such modeling frameworks can drastically increase the efficiency of resource allocation efforts for other diseases. The PSS intervention and modeling framework will be developed in the R61 phase (R61 Aims 1 and 2) and implemented in the R33 phase to systematically deliver MHCs with PSS services to the highest priority communities (identified via modeling) in South Carolina (SC) in order to increase MOUD treatment initiation, retention, and overdose prevention. In the R33 phase, we will conduct a randomized controlled trial (RCT) to evaluate the effectiveness of the PSS intervention component (R33 Aim 1), and extend our modeling framework developed in the R61 phase in order to a) evaluate the population impact and cost-effectiveness of the PSS intervention on preventing fatal overdose (R33 Aim 2a) and b) explore improvements to MHC protocols in order to increase effectiveness of MHC-based interventions for OUD (R33 Aim 2b). With opioid overdose deaths doubling over the past 2 years nationally and in SC, there are no signs that the epidemic is slowing down. Our sustainable framework has potential to prevent hundreds to thousands of opioid overdoses in SC alone, and can be scaled up in other regions to save many more lives.