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Objectives: To identify and value resources required to implement and sustain the Massachusetts model of office-based addiction treatment (MA Model) in the Primary Care Opioid Use Disorders Treatment trial (NCT03407638) using a nurse care manager (NCM) to support medication for opioid use disorder in primary care settings.

Study design: A site-specific microcosting analysis was conducted via activity-based costing. Guided by a structured costing instrument, we conducted semistructured interviews with relevant personnel and assigned nationally representative costs.

Methods: Data came from 6 health care systems. Costs were categorized as fixed start-up, time dependent, or variable and estimated as annual per-clinic and per-patient costs for implementation and sustainment phases.

Results: Mean implementation cost (ie, year 1 fixed start-up, time-dependent, and variable) was $238,888 per clinic ($3185 per patient); each subsequent year cost $229,676 ($3062 per patient), assuming 75 patients per month and 29% new patient case mix. Mean onetime fixed start-up costs were $9212 per clinic and included supplies and training. Time-dependent costs were $70,446 per clinic and included rent and meetings. Variable costs were $159,229 per clinic and included NCMs’ and prescribers’ clinical duties. On average, NCMs spent 1967.6 hours on MA Model-related work per year (26.2 hours per patient). In sensitivity analyses, costs varied drastically with patient caseload, provider mix, and new patient case mix.

Conclusions: Fixed start-up and time-dependent costs were minimal. Variable costs were 66.7% of implementation costs and 69.3% of costs annually afterward. The primary cost driver was NCM time conducting MA Model-related work. The additional value of the model will depend on associated downstream outcomes. These results may be helpful to health care systems considering implementing the MA Model.

Related protocols: CTN-0074

This is the primary outcomes article for CTN-0080-A-2. Introduction: Racial and ethnic inequities persist in medication treatment initiation and adherence for pregnant and postpartum people with opioid use disorder (OUD). Our objective was to understand the experiences of “positive outliers,” specifically pregnant and postpartum people of color with OUD who utilized medication treatment and engaged in a randomized clinical trial for buprenorphine despite historical, cultural, and structural barriers.

Methods: We conducted two sets of semi-structured qualitative interviews. First, trained peers with lived expertise as mothers in recovery interviewed individuals who identified with a non-white race and/or ethnicity and enrolled in the Medication Treatment for OUD in Expectant Mothers (MOMs) trial (NCT03918850). Second, we interviewed principal investigators, clinicians, and research coordinators from the 13 MOMs trial sites. We used an inductive thematic approach informed by the Social Ecological Model of Racism and Anti-Racism. Transcripts were double-coded and reviewed until consensus was reached. Preliminary findings from participant and staff interviews were merged and triangulated with peers to inform theme development.

Results: We completed 17 interviews with MOMs trial participants from 7 sites. Participants identified as Hispanic (29%), Black non-Hispanic (24%), multi-racial Hispanic (18%), multi-racial non-Hispanic (18%), and American Indian, Native Hawaiian, or Pacific Islander (12%). Thirty-two interviews with trial staff were also completed. Three themes emerged: (1) Although some participants expected racist treatment and research exploitation, all participants interviewed reported non-discriminatory, non-judgmental care within the MOMs trial; (2) Compassionate care, frequent, personalized, and integrated encounters, and emotional support helped counteract prior stigmatizing and discriminatory health care interactions, enabling participants of color to feel particularly supported, trusted, and empowered during the MOMs trial; and (3) Despite pervasive cultural stigma around addiction and concerns about taking an investigational drug while pregnant, participants expressed that pregnancy status, care team trust, and transparent communication with MOMs trial staff encouraged medication utilization and adherence.

Conclusion: Facilitators of successful engagement in the MOMs trial and retention in medication treatment among pregnant and postpartum people of color with OUD included non-judgmental care, sustained trust, and frequent contact. Key perinatal OUD clinical interventions and trial improvements include personalized communication and scheduling flexibility to promote engagement of marginalized populations.

Related protocols: CTN-0080-A-2

Objectives: To estimate all-cause and cause-specific mortality burden in patients who received medication treatment for opioid use disorder (OUD).

Methods: We (the CTN Health Systems Node) conducted a cohort study of 27,230 patients who received medications for opioid use disorder (MOUD), buprenorphine or naltrexone, matched 1:1 to individuals without MOUD from 4 US health systems in California, Colorado, and Michigan between 2012 and 2021. We calculated standardized mortality ratios (SMRs) with bootstrapped 95% CI to assess mortality burden.

Results: Patients who received treatment for OUD were 4 times more likely to die from any cause (SMR 4.37, 95% CI 3.80-4.64) and 37 times more likely to die from drug overdose (SMR 37.58, 95% CI 29.33-55.09; 41.6% of all deaths) compared to demographically similar individuals. Deaths from non-overdose causes showed modest but significant burden (SMR 2.68, 95% CI 2.31-2.86; 58.4% of deaths). The top contributors to non-overdose deaths were circulatory system diseases (SMR 3.06, 95% CI 1.73-3.63; 13.9% of deaths), other external causes (SMR 4.50, 95% CI 3.64-5.62; 11.3% of deaths), and cancers (SMR 1.59, 95% CI 1.30-1.86; 9.4% of deaths), which all showed elevated mortality.

Conclusions: Continued efforts are needed to prevent high burden of mortality from both overdose and non-overdose causes among patients with MOUD treatment.

Background: Rural communities face disproportionate rates of opioid use disorder (OUD) and overdose mortality but continue to be underrepresented in clinical research and underserved in access to medications for opioid use disorder (MOUD). Structural barriers including shortages of qualified providers, transportation challenges, and stigma limit uptake of evidence-based treatment. To address these gaps, the National Drug Abuse Treatment Clinical Trials Network (CTN) launched two pragmatic trials focused exclusively on rural populations: CTN-0102, a telemedicine (TM) feasibility study connecting rural primary care patients to external MOUD providers, and CTN-0102XR (RXR), a pilot randomized trial evaluating extended-release buprenorphine (Brixadi®) compared to sublingual buprenorphine-naloxone.

Objective: The article aims to describe the implementation of these two rural pragmatic trials, identify challenges encountered in study implementation, and present lessons learned. We applied frameworks from implementation science, including the Consolidated Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementing Change (ERIC), to demonstrate how pragmatic trial implementation mirrors implementation of evidence-based programs and practices, and can benefit from established implementation frameworks and strategies.

Results: Across 13 rural clinics in 10 states, both trials demonstrated the feasibility of integrating MOUD into primary care settings through pragmatic study designs closely aligned with routine clinical workflows. Principal challenges included limited clinic research capacity, staff stigma toward OUD treatment, communication barriers between local clinics and external TM vendors, and variable digital access. Solutions included engaging local champions, co-developing workflows tailored to each clinic’s operations, simplifying technology requirements, and emphasizing bi-directional communication among clinic, research, and vendor teams. Continuous technical assistance and protocol flexibility and adaptation were crucial for sustaining engagement and aligning study procedures with clinical realities. Findings demonstrated that rural clinics can feasibly implement TM-based MOUD coordination and extended-release buprenorphine with adequate support and contextual adaptation.

Conclusions: Lessons from CTN-0102 and CTN-0102XR underscore that pragmatic trials in rural settings benefit from early contextual assessment, engagement of community stakeholders, adaptable protocols, and strong implementation support. Applying implementation science frameworks facilitates solutions to real-world barriers and enhances study sustainability. Future CTN efforts should continue to prioritize rural site inclusion, capacity building, and equitable access to evidence-based OUD treatment.

Related protocols: CTN-0102, CTN-0102-XR

Importance: Health plan disenrollment may interrupt treatment for opioid use disorder (OUD) and overall care, increasing risk for serious outcomes, including overdose and death. There is limited evidence on the association of disenrollment with all-cause and overdose mortality after initiating medications for OUD (MOUD) treatment.

Objective: To assess the association of health plan disenrollment with all-cause and overdose mortality in patients treated with MOUD.

Design, setting, and participants: This cohort study conducted by the CTN Health Systems Node, included privately and publicly insured patients aged 16 years or older who initiated buprenorphine or naltrexone for OUD treatment between January 1, 2012, and December 31, 2021, at 3 integrated health insurance and care delivery systems in 2 US states. Patients were followed up to 2 years until December 31, 2022. Data were analyzed July 2024 to November 2025.

Exposure: Health plan disenrollment following MOUD initiation.

Main outcomes and measures: All-cause mortality and drug-related and alcohol-related overdose mortality within 2 years of MOUD initiation ascertained from the National Death Index. Survival analyses were adjusted for patient sociodemographic and clinical characteristics.

Results: Among 20,011 patients (mean [SD] age 38.7 [15.1] years; 12 299 males [61.5%]) who were treated for OUD, 6948 (34.7%) experienced disenrollment and 586 (2.9%) died during follow-up. The crude rate was 15.3 (95% CI, 14.1-16.6) per 1000 person-years for all-cause mortality and 6.2 (95% CI, 5.4-7.0) per 1000 person-years for overdose mortality. Ever experiencing disenrollment showed elevated all-cause mortality (17.6 [95% CI, 14.9-20.8] vs 14.7 [95% CI, 13.4-16.1] per 1000 person-years) and overdose mortality (8.9 [95% CI, 7.1-11.3] vs 5.4 [95% CI, 4.7-6.3] per 1000 person-years) relative to remaining enrolled. In adjusted analyses, ever experiencing disenrollment was associated with increased hazards of all-cause (hazard ratio [HR], 1.51; 95% CI, 1.23-1.84) and overdose mortality (HR, 1.56; 95% CI, 1.17-2.09). Compared with remaining enrolled and receiving MOUD treatment, being disenrolled (HR, 4.34; 95% CI, 3.19-5.89) and being enrolled and not receiving MOUD treatment (HR, 4.19; 95% CI, 3.24-5.43) were associated with overall mortality.

Conclusions and relevance: In this cohort study of patients who initiated MOUD, experiencing health plan disenrollment was associated with increased mortality risk compared with remaining enrolled. Strategies are needed to improve continuity of health coverage and mitigate the elevated mortality risk during insurance transitions for patients receiving medications for OUD.

Background and aim: Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial.

Methods: Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success.

Results: 204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89).

Conclusions: Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.

Related protocols: CTN-0051

Medications for opioid use disorder (MOUD), such as methadone, buprenorphine, and extended-release naltrexone (XR-NTX), have been shown to reduce or eliminate opioid use and craving, protecting against opioid overdose and death. Stopping medication is associated with risk of relapse and potential overdose. Unsurprisingly, patients may desire to stop MOUD because of adverse effects, burden, or preference for recovery without medication, asking, “How long do I need to take medication?” Clinicians who treat OUD often encounter this uncomfortable risk-benefit discussion with patients who want to stop MOUD, hoping that the patients can do so successfully, while acknowledging the major risks. Prospective data are needed to inform those discussions. In designing one of the first clinical trials focused on MOUD discontinuation—the Discontinuation Phase of the Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD) trial (NCT04464980)2—the investigators identified ethical issues that needed consideration in designing the study.

The authors of this Viewpoint are study investigators, including a social worker (S.E.P.) and 2 psychiatrists experienced with MOUD (R.D.W. and E.V.N.). In this Viewpoint, we describe those ethical challenges and our attendant solutions to inform the design of other studies of medication discontinuation, where discontinuing treatment could have grave consequences.

Related protocols: CTN-0100

Background: Rural communities continue to experience high overdose mortality rates and challenges retaining individuals with opioid use disorder (OUD) on medications for opioid use disorder (MOUD). The most recent formulation of injectable extended-release buprenorphine (XR-BUP) may improve treatment engagement and outcomes for people with OUD.

Objectives: The RXR study (CTN-0102-XR) aims to evaluate the feasibility of implementing XR-BUP in rural settings, acceptability of XR-BUP to clinic staff and patients, and effectiveness of XR-BUP compared with sublingual buprenorphine-naloxone (SL-BUP).

Study design and methods: This is an open-label randomized controlled trial (RCT) using intention-to-treat (ITT) analysis. Approximately 144 participants recruited from seven rural clinic sites will be randomized to receive XR-BUP or SL-BUP in a ratio of 2:1, and will receive study medication for 14 weeks. Participants in the XR-BUP condition will receive two weekly initiation dosages, followed by the target monthly dosage (128 mg) at Weeks 2, 6, and 10. Participants in the SL-BUP condition will receive medication on a similar schedule, with a target dose range of 16-24 mg/day. The main comparative effectiveness outcome measure is the number of monthly opioid negative urine drug screens (UDS) for non-prescribed opioids from Weeks 2-14. Feasibility and acceptability will be evaluated using mixed methods, combining participant survey and interview data from clinic administrators, providers, and patients.

Conclusions: If demonstrated to be feasible and acceptable to participants and staff and there is evidence of effectiveness for people with OUD in reducing opioid use, XR-BUP may be considered an important option for addressing OUD in rural settings.

Related protocols: CTN-0102-XR

Importance: Hospital-based opioid treatment (HBOT) can improve outcomes for patients with opioid use disorder, but little is known about specific attributes and supports needed for clinical champions to successfully implement HBOT.

Objective: To identify characteristics and supports of effective clinical champions implementing HBOT in US hospitals.

Design, setting, and participants: Qualitative study using postimplementation semistructured interviews conducted with individuals highly involved in HBOT implementation, including champions and hospital staff at 12 US community hospitals randomized to the high-intensity group of the Exemplar Hospital Initiation Trial to Enhance Treatment Engagement, a national implementation trial comparing low- and high-intensity HBOT implementation strategies. Interviews explored implementation experiences over 24 months from December 2021 to December 2023. Interviews were audio recorded, transcribed, and coded. The framework method and in-depth thematic analysis were used to explore the role of champions.

Interventions: All hospitals received a best-practices manual, video webinar series, and hub team support for questions, while hospitals randomized to the high-intensity group also received monthly practice facilitation, telementoring, and 10% effort funding for a local champion. Champions led HBOT implementation with support from regional hubs with HBOT expertise.

Measures: Effective champions were defined as those perceived by staff to successfully lead HBOT implementation. Open-ended questions and thematic analysis explored participants’ perspectives on attributes of effective champions and how they overcame implementation barriers.

Results: A total of 31 hospital staff (15 physicians, 5 executives, 5 pharmacists, 2 nurse practitioners, 2 social workers, 1 nurse, and 1 addiction counselor) were interviewed. Effective champions were perceived as respected hospital “insiders” with institutional influence, persistence, and systems change skills. They built multidisciplinary teams, developed standard workflows, and used emotionally resonant strategies (eg, patient narratives) to overcome stigma and engage hospital leadership. Champions could be effective without addiction medicine expertise, particularly when provided with protected time, hospital leadership support, and external practice facilitation from addiction experts.

Conclusions and relevance: This multisite qualitative study underscores the vital role of champions in expanding hospital-based opioid care. To ensure HBOT expansion, hospitals should invest in champions, protected time, leadership backing, and external supports that legitimize and routinize evidence-based addiction care.

Related protocols: CTN-0098

Primary care is a critical setting to provide care for the 75-79% of patients who have opioid use disorder (OUD) but do not receive medications for OUD. However, patient perceptions of primary care of OUD are not well understood. Patients completed surveys about their experience with opioid-related clinical decision support system (CDSS) printouts and OUD treatment in the first 7-9 months of implementation of an OUD-CDSS. Survey responses were presented overall and by reason for study eligibility. Of 277 patients completing surveys, 22% recalled seeing the printouts; of these, 85% said the printouts made them more comfortable discussion opioid risk. Of all respondents, half discussed opioids during their visit; of these, 84% felt conversations were conducted sensitively. Overall, 88% felt primary care was the right setting to discuss opioid risks. The opioid-related printouts and discussions were generally well-received, and patients felt primary care was a suitable setting for opioid-related care.

Background: Opioid use disorder (OUD) remains a significant public health issue. Yet, few primary care clinicians (PCCs) screen for, diagnose, or treat OUD. Clinical decision support tools (CDS) integrated into the electronic health record improve process and outcome measures across a variety of conditions. We evaluated PCC perspectives on an OUD CDS tool (Opioid Wizard) deployed through a clinic-randomized trial.

Methods: This is a secondary analysis of CTN-0095, a trial evaluating the effectiveness of Opioid Wizard on OUD process and outcome measures. In short, 92 primary care clinics across three health systems were randomized to Opioid Wizard or usual care. PCCs completed online surveys pre- and 9-month post-Opioid Wizard’s go-live date. Survey items measured PCC self-reports on their confidence and ability to manage OUD, and for PCCs in Opioid Wizard clinics, perceptions about the tool. Generalized linear mixed models with Poisson distribution estimated change in survey response from baseline to follow-up within each treatment group (risk ratios) and in intervention relative to control clinics (ratio of risk ratios).

Results: 361 PCCs (n = 180 Opioid Wizard, n = 181 usual care, 63% female) answered at least one survey. Confidence in screening (RR 1.32, 95% CI 1.07, 1.62), diagnosing (RR 1.24, 95% CI 1.02, 1.50), and referring (RR 1.17, 95% CI 1.02, 1.34) patients for OUD care significantly increased in Opioid Wizard clinics only. Confidence in treating OUD with buprenorphine did not increase in either setting. Of 55 PCCs who used Opioid Wizard at least once, 80% agreed Opioid Wizard made tasks easier and 70% agreed using Opioid Wizard was time “well spent,” but only 44% were likely to recommend it to colleagues.

Conclusion: Opioid Wizard increased PCC confidence across a variety of OUD care measures yet enthusiasm for and use of the tool was limited. Efforts to increase Opioid Wizard use may improve OUD care measures.

Related protocols: CTN-0095

This is the primary outcomes article for CTN-0080. Importance: Treating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation.

Objective: To evaluate the effectiveness and safety of extended-release buprenorphine vs sublingual buprenorphine for OUD in pregnancy through 12 months post partum.

Design, setting, and participants: This 2-group, open-label, noninferiority, randomized clinical trial was conducted between July 2, 2020, and October 30, 2024, among adults with OUD and a singleton pregnancy of 6 to 30 weeks’ gestational age at 13 outpatient cross-disciplinary peripartum OUD treatment sites.

Interventions: Randomization to sublingual or extended-release buprenorphine (weekly formulation during pregnancy, monthly formulation optional post partum if not breastfeeding).

Main outcomes and measures: The primary and key secondary outcomes were illicit opioid abstinence during pregnancy and the postpartum period, respectively, defined as the proportion of weekly collected urine samples negative for illicit opioids. If noninferiority was demonstrated at a margin of 0.15, testing for superiority was planned. Key secondary infant outcomes from medical records were opioid treatment for neonatal opioid withdrawal syndrome (NOWS; yes or no) and number of opioid treatment days for NOWS.

Results: Among 140 randomized participants, the mean (SD) age was 31.2 (4.6) years. There were 10 Black participants (7.1%), 10 Hispanic participants (7.1%), 116 (82.9%) White participants, and 14 participants (10.0%) who belonged to additional groups. All but 2 were already prescribed sublingual buprenorphine. Study completion was 98% through pregnancy (137 participants) and 81% through 12 months post partum (114 participants). Illicit opioid abstinence was higher during pregnancy for participants receiving extended-release vs sublingual buprenorphine (82.5% vs 72.6%; mean difference, 9.84 [95% CI, 1.72 to 17.95] percentage points; P = .009). Postpartum abstinence rates declined and were similar in both groups (60.2% vs 59.5%; mean difference, 0.65 [98% CI, -12.72 to 14.02] percentage points; P = .45). Those receiving extended-release buprenorphine experienced fewer serious adverse events during pregnancy (8.7% vs 26.8%; P = .007) and post partum (6.0% vs 18.6%; P = .04). Nonserious adverse events rates did not differ between groups, but more were deemed medication-related for extended-release participants during pregnancy (26.1% vs 7.0%; P = .003). Infants exposed to extended-release vs sublingual buprenorphine did not differ in need for opioid treatment (30.2% vs 26.5%; relative risk, 1.14 [98% CI, 0.54 to 1.99]; P = .64) or mean (SE) treatment days (10.9 [2.2] vs 14.8 [3.0] days; relative risk, 0.73 [98% CI, 0.36 to 1.51]; P = .28). At birth, extended-release-exposed neonates had larger mean (SE) head circumferences than those exposed to sublingual buprenorphine (34.0 [0.2] vs 33.4 [0.2] cm; mean difference, 0.63 [95% CI, -0.00 to 1.26] cm; P = .049).

Conclusions and relevance: The findings of this randomized clinical trial support weekly extended-release buprenorphine for OUD treatment during pregnancy.

Related protocols: CTN-0080

Background and objectives: Patients using fentanyl have worse treatment outcomes; however, little is known about other drugs that complicate treatment.

Methods: A national survey (n = 396) was conducted for CTN-0135 using a random sample of clinicians waivered to prescribe buprenorphine in the United States. This study reports the results of a single survey item on clinicians’ perceptions of other drugs, besides IMF, complicating treatment.

Results: Clinicians reported methamphetamine (86.4%), synthetic cannabinoids (42.7%), and xylazine (41.4%) were complicating treatment; reports varied by geographic region.

Conclusions and scientific significance: Rapid clinician surveys can provide real-time data on changing patterns of drug use’s impact treatment outcomes.

Related protocols: CTN-0135

Background: Most people with opioid use disorder (OUD) do not receive evidence-based treatment. To increase treatment rates, primary care clinics may choose to implement risk prediction tools available in the electronic health record (EHR) to identify patients with a high risk of OUD or overdose.

Objective: To externally validate Epic’s cognitive computing model to predict the Risk of Opioid Abuse or Overdose (referred to as the Opioid Risk Score; ORS) in three large integrated health systems.

Design: Prospective cohort study secondary to an ongoing clinical trial.

Participants: Patients (N = 704,764) aged 18-75 who had a primary care encounter during the study period (April 2021-December 2022) and did not have an OUD diagnosis at index.

Main measures: Data were extracted from the EHR. The index date was defined as the first date within the study period where the patient met eligibility criteria and had an ORS calculated by the EHR. The binary outcome variable was whether the patient was diagnosed with OUD or experienced an opioid overdose within 12 months of the index date.

Key results: Most patients were classified as low risk on ORS (99.6%). Few patients experienced an OUD diagnosis or overdose in the 12-month follow-up period (0.3%). The model correctly classified 185 of 2362 patients who experienced an event (sensitivity 0.0783, 95% CI 0.0675, 0.0892) and 699,926 of 702,406 patients who did not experience an event (specificity 0.9965, 95% CI 0.9963, 0.9966). Few patients with high ORS experienced the event (PPV 0.0694, 95% CI 0.0598, 0.0791). The model had excellent discrimination (c-statistic = 0.815) but was poorly calibrated, underestimating risk for patients who experienced the outcomes.

Conclusions: Epic’s ORS demonstrated excellent discrimination but very low sensitivity across three large integrated health systems. Health systems should exercise caution before implementing vendor risk prediction models without validating their use in their patient populations.

Related protocols: CTN-0095

This editorial in JAMA describes the outcomes and implications of the primary outcomes paper for CTN-0099, the ED-INNOVATION trial, which compared the use of a 7-day extended-release buprenorphine injection to 7 days of sublingual buprenorphine for patients in the ED presenting with opioid use disorder and found no difference in treatment engagement at 7 days or 30 days among the two groups. They also reported low rates of precipitated withdrawal in both groups, despite a high rate of fentanyl use.

In the context of an ongoing public health emergency related to drug toxicity deaths, emergency department visits are undeniably important opportunities to identify people with high-risk opioid use and engage them in care. Increasing access to evidence-based harm reduction and treatment options for people with OUD in EDs is a crucial aspect of the response to this public health emergency.

Increasing the choices of opioid agonist therapies available in EDs is important. Providers should be careful to monitor their own biases regarding which approach might work best for an individual patient (for example, many providers might assume an injection is the easiest or best approach for a patient, while the patient may feel differently).

This study provides further evidence that EDs can and must lead ED-specific studies and initiatives that confirm best practices and increase access to lifesaving opioid agonist therapies. The way forward requires that clinician-scientists continue to foster a discussion of what is possible in EDs, while prioritizing patient-centered decision-making and consent, and clearly establishing both safety and benefit of interventions prior to implementation.

Related protocols: CTN-0099