The OUD Cascade of Care and Critical Outcomes: Longitudinal Linkage with Opioid Use - The OUD Cascade of Care and Critical Outcomes: Longitudinal Linkage with Drug Use Dramatic increases in overdose deaths in the US have created an urgent need to improve access to and retention in evidence-based care for opioid use disorder (OUD) with medication (MOUD), under the OUD Cascade of Care framework. The Cascade model emphasizes key stages or transitions during the treatment of individuals with OUD to reduce risks of adverse outcomes: critically, successful MOUD initiation and long-term retention. However, it has thus far been agnostic towards concurrent opioid use. In the era of rising fentanyl prevalence in the illicit drug supply, public health frameworks need to adjust for environmental conditions that may impact clinical outcomes. Our research approach draws from a conceptualization of opioid use, treatment response, and adverse outcomes as evolving along trajectories, over varying timeframes emphasizing the need for harm reduction approaches tailored to patient goals as they evolve over time. While we hypothesize that greater exposure to fentanyl in the local drug supply will impede successful treatment engagement, we also expect longer durations of buprenorphine treatment to protect against overdose risk, even among patients with intermittent opioid use while in care. However, patients with opioid use in care will likely experience attenuated risk reductions following treatment discontinuation. There is a critical need for longitudinal analyses of treatment pathways and outcomes, including the intersecting roles and prognostic significance of toxicology results and treatment retention, and their relationship to overdose risk during and following treatment. Because current evidence concerning optimal durations of care, especially at the individual patient or sub-population level, is lacking, there is currently little empirical evidence to guide clinicians and health systems regarding how to best tailor service provision and estimate risks of adverse events at the patient level. Our proposal seeks to fill these critical gaps in knowledge. We will link EHR records for 95,000 individuals from a multi-state buprenorphine provider-- the nation’s largest OBOT provider-- with Medicaid claims and National Death Index (NDI) data to create a new, unique, integrated database spanning 2014-2022 in a dozen states to observe patients before intake, at baseline, and while in care over multiple years, accounting for mortality during the onslaught of fentanyl. Medicaid is now the largest payer for MOUD. Our findings will have broad implications for clinical care, policy, systems design, quality measurement development, and healthcare administration. Our goal is to establish an empirical evidence base to inform clinical evaluations of patient risks (e.g. adverse outcomes including overdose) at the individual level. Against the scale and gravity of the evolving opioid epidemic, it is vital that clinical and policy strategies are informed by careful consideration of rigorous analyses of empirical data with large, usual-care populations across state lines.