Enhancing buprenorphine low dose initiation (COPILOT)

Overdose deaths continue to surge in the United States, with more than 100,000 deaths in 2021, largely driven by fentanyl. Buprenorphine is a highly effective medication for opioid use disorder (OUD) that reduces overdose deaths and opioid-related harms. Yet fewer than 20% of individuals with OUD receive buprenorphine, and fear of withdrawal during initiation—particularly precipitated withdrawal among people using fentanyl—remains a major barrier. Traditional initiation requires opioid abstinence and the presence of withdrawal, a process that many patients find intolerable. In response, clinicians have developed alternative initiation strategies, including Low-Dose Initiation (LDI), which gradually introduces buprenorphine over several days, and Direct-to-Inject (DTI), which begins treatment with an extended-release injectable formulation. Both approaches reduce the risk of precipitated withdrawal, but completion and retention remain suboptimal, and strategies to enhance their effectiveness are lacking. The proposed training and research plan for this K23 application will allow Dr. Leslie Suen to acquire the skills necessary to become an NIH-funded independent clinician investigator with expertise in implementation science and intervention development to improve OUD treatment outcomes. Guided by a strong mentorship team, Dr. Suen will apply advanced methods in intervention development, mixed methods research, and randomized trial design to develop and pilot an Enhanced Buprenorphine Initiation (EBI) program. EBI will combine DTI-focused initiation strategies with implementation science–guided enhancements (e.g., targeted education, daily check-ins, contingent incentives). The project includes: (1) identifying barriers to LDI completion; (2) designing the EBI program using participatory methods; and (3) piloting EBI in a randomized controlled trial at the San Francisco Outpatient Buprenorphine Induction Clinic. This work will establish the foundation for a future R01 to evaluate EBI’s effectiveness and advance the ultimate goal of improving buprenorphine uptake and reducing overdose deaths.