PROJECT SUMMARY The proposed study addresses a critical knowledge gap: How to best implement digital treatments for opioids and other substance use disorders (SUDs) in primary care (PC). reSET and reSET-O are smartphone-based, FDA-cleared versions of the Therapeutic Educational System, which is a computerized cognitive-behavioral treatment for SUDs. We will study their implementation into PC to potentially improve care for people with SUDs, and as a model for how to sustainably implement digital treatments into real-world healthcare. Digital treatments could extend the reach of SUD therapy to more people and could address a significant barrier to buprenorphine prescribing in PC: the lack of access to psychosocial treatment. Delivery system leaders in Kaiser Permanente Washington are our collaborators for studying strategies for implementing reSET and reSET-O in Washington State to address prior implementation challenges documented in the literature. After piloting in 2 clinics, we will randomize up to 23 PC clinics in a 2x2 factorial design to four approaches: (1) “standard implementation,” which is an evidence-based implementation strategy previously used by our delivery system partners; (2) “standard implementation with external facilitation,” a clinician-facing implementation strategy; (3) “standard implementation with patient coach,” a patient-facing implementation strategy using medical assistants to support patient adoption and engagement; and (4) “standard implementation with both.” These implementation strategies have some evidence in PC, but their impact on real-world implementation of a digital treatment has not been evaluated. Specific Aims are to (1) Estimate the effect of clinician-facing (external facilitation) and patient-facing (patient coach) implementation strategies in increasing the reach and fidelity of a digital SUD treatment in PC clinics, and (2) compare the population-level cost-effectiveness of each implementation strategy in increasing reach, fidelity, and abstinence by patients. This administrative supplement will allow our study to recover from COVID-related delays and (3) estimate the impact of: training non-social work clinicians to prescribe reSET and reSET-O, allowing prescriptions without requiring follow-up visits, and centralizing the administrative tasks of prescribing. IMPACT: Researchers and health systems do not know how to reach large numbers of patients with OUDs and other SUDs. Digital treatments are promising, but health systems lack evidence to guide implementation of digital therapies. This study will estimate and compare the effectiveness of clinician-facing and patient-facing implementation strategies, providing health system leaders with data on how to best implement digital treatments.