PROJECT SUMMARY/ABSTRACT Overdose deaths are surging in the United States, mainly due to non-medical fentanyl use. Buprenorphine is a highly effective medication for opioid use disorder (OUD), reducing overdose deaths and other opioid-related harms. However, uptake of buprenorphine remains low, in part, due to concerns of precipitated withdrawal among individuals using fentanyl during traditional buprenorphine initiation. To overcome this barrier, clinicians have begun using Low Dose Initiation (LDI) protocols. LDI protocols introduce small amounts of buprenorphine that are gradually increased until a therapeutic dose is reached, minimizing risk for precipitated withdrawal. The San Francisco Outpatient Buprenorphine Induction Clinic (OBIC) has been offering LDI protocols since 2020. Our preliminary findings note that LDI protocols are now the prevailing strategy to initiate buprenorphine among patients using fentanyl in San Francisco, though successful completion and retention rates remain low. Substantial knowledge gaps exist regarding barriers to LDI completion and ideal strategies to enhancing LDI use. The proposed training and research plan for this K23 application will allow Dr. Leslie Suen to acquire the skills necessary to achieve her career goal of becoming an NIH-funded independent clinician investigator with expertise in implementation science and developing interventions to improve treatment outcomes for individuals with OUD. With the guidance of her dedicated mentoring team and rigorous training plan, Dr. Suen will apply advanced skills in intervention development, mixed methods, and randomized trial design and evaluation to develop and pilot an Enhanced LDI program. Enhanced LDI will leverage implementation science frameworks to test various behavioral interventions to increase successful buprenorphine initiation and retention. Building on Dr. Suen’s prior research in OUD treatment outcomes and LDI use, this proposal addresses the following aims: 1) identify challenges and barriers to LDI completion using in-depth interviews with patients, clinicians, and system leaders; 2) design an Enhanced LDI program using focus groups of patients, practitioners, pharmacists, and other healthcare staff to test strategies for improving buprenorphine uptake; 3) evaluate the preliminary impact of the Enhanced LDI program on successful initiation and retention through a 6-month pilot randomized controlled trial (RCT) with patients with OUD using fentanyl, comparing Enhanced and Usual LDI treatments. The evaluation will use various data sources to assess successful initiation, acceptability, and feasibility. This proposal has the goal of improving and developing novel interventions for OUD treatment in real-world settings, and it aligns with Dr. Suen’s career development plan to gain expertise in intervention development, mixed methods, and randomized trial and evaluation. The findings of this proposal will lead to an R01 application to test Enhanced ...