Project Summary The opioid crisis is dynamic. To overcome barriers to addiction treatment, implementation research must keep pace with the changing landscape of the opioid crisis by more rapidly adapting to emerging evidence. Clinical decision support (CDS) offers a promising implementation strategy to more efficiently operationalize and scale evidence-based practices. Patients are motivated to initiate addiction treatment after sentinel events, such as an emergency department (ED) visit for opioid overdose. Unfortunately, clinicians rarely initiate addiction treatment. To that end, we recently conducted the EMBED pragmatic cluster-randomized trial. This trial evaluated the effectiveness of non-interruptive electronic health record (EHR)-based CDS to facilitate patient assessment and automate EHR activities to implement ED-initiation of buprenorphine in the routine care of people with opioid use disorder (OUD). The EMBED CDS increased the proportion of physicians who initiated buprenorphine leading to national dissemination of EMBED. Post-trial analysis identified disparities in treatment as well as opportunities to increase reach and adoption. However, CDS interventions typically remain unchanged while being studied and traditional methods for evaluation are time-consuming, resulting in missed opportunities for progress and delays in implementing effective interventions. These limitations must be addressed to speed the implementation of evidence-based solutions to the opioid crisis in general and the the nationally scaled EMBED CDS specifically. The EHR can both deliver CDS interventions and offer a non- obtrusive, rigorous way to study care delivery at scale utilizing EHR use measurement with automated log data capture. Current quantitative CDS use and usability metrics are limited to alert dismissal rates and descriptive measures of CDS characteristics but are not capable of evaluating CDS interfaces and workflows such as granular assessment of CDS uptake and usability. Therefore, we will adapt CDS of best practices in the care of people with OUD using a Multiphase Optimization STrategy (MOST) framework including rapid, serial randomized testing, measured by scalable, pragmatic EHR use metrics to achieve the following specific aims: (1) Refine and validate reproducible, scalable outcome measures for assessing CDS uptake and usability to implement ED-initiation of buprenorphine for OUD and (2) Refine and evaluate a multicomponent CDS intervention to improve ED-initiation of buprenorphine in patients with OUD via increased CDS uptake, usability, and equity. Achievement of these specific aims will offer a pathway to scalable, equitable interventions for the opioid crisis by innovating data-driven, adaptive approaches that increase treatment access and engagement for people with OUD. With expertise in emergency medicine, addiction medicine, clinical decision support, pragmatic evaluation, biostatistics, health equity, and data, measurement, and im...