This study is testing whether offering buprenorphine treatment directly at syringe service programs (SSPs) helps more people start and stay in treatment for opioid use disorder (OUD) than referring them to community buprenorphine treatment providers. Buprenorphine is a medication that helps reduce opioid cravings and withdrawal symptoms.

The study compares two ways of connecting people to treatment:

Referral to a community treatment provider (usual care before the new program begins).

Onsite, low-threshold buprenorphine treatment at the SSP, which allows participants to start medication quickly and without having to establish care at another provider.

Participants will be adults who have opioid use disorder and are SSP clients. Each SSP will begin offering the new onsite buprenorphine program at different times during the study. Researchers will collect information before and after the new program begins to see how it affects treatment engagement and health outcomes.

The study will also examine how easy or difficult it is for SSPs to start and run the new program, how acceptable it is to staff and participants, and whether it is cost-effective.

The overall goal is to find better ways to expand access to life-saving opioid treatment in community-based settings.

This is a Type 1 hybrid effectiveness-implementation study designed to evaluate the impact and feasibility of implementing low-threshold buprenorphine (BUP) treatment at syringe service programs (SSPs) in order to improve access to and retention in medications for opioid use disorder (MOUD) treatment among people with moderate to severe opioid use disorder (OUD). The study seeks to understand whether the low-threshold approach improves participant-level outcomes and how SSPs can successfully implement and sustain this model.

Study Design

The study uses a cluster randomized stepped wedge design, in which eight SSPs will be randomly and sequentially assigned to begin implementing the low-threshold BUP program until all sites have transitioned from the referral condition to the intervention condition. This design allows each site to serve as its own control and ensures equitable access to the intervention over time. The stepped wedge design also facilitates examination of temporal effects, while accounting for differences in local environments and SSP readiness for implementation.

Participants will be recruited across the eight SSPs in different geographic regions of the United States. SSPs will be selected to represent a range of community types (urban, suburban, and rural) and to reflect varying policy environments related to MOUD access.

Study Rationale and Background

Despite robust evidence that buprenorphine reduces overdose deaths and improves recovery outcomes, access to this medication remains limited, especially among people who use drugs and have difficulty navigating the healthcare system. Low-threshold buprenorphine models aim to reduce barriers by emphasizing same-day access, flexibility, and a treatment orientation that meets participants "where they are."

SSPs provide a trusted, nonjudgmental environment and are uniquely positioned to engage individuals who are at highest risk for overdose and least likely to access formal treatment. Integrating buprenorphine prescribing directly within SSPs could substantially expand access to life-saving treatment in community settings.

Study Objectives

Primary Objective:

To evaluate the effectiveness of low-threshold BUP treatment at SSPs compared to treatment as usual (TAU) for increasing 3-month retention in buprenorphine treatment.

Secondary Objectives:

Assess buprenorphine adherence, additional OUD treatment outcomes, and health-related quality of life.

Examine the cost-effectiveness of implementing low-threshold BUP at SSPs from both payer and societal perspectives.

Characterize implementation outcomes-adoption, acceptability, appropriateness, feasibility, reach, fidelity, and sustainability-across diverse SSP settings.

Exploratory Objectives:

Explore participant-level moderators (e.g., polysubstance use, co-occurring mental health conditions, housing status, rurality) that may predict outcomes or differential intervention effects.

Identify contextual determinants (organizational capacity, policy environment, leadership engagement) associated with successful SSP implementation.

Study Procedures

Participants will complete study assessments at baseline, 1 month, 3 months, and 6 months post-enrollment. Measures will include substance use patterns, treatment engagement, overdose events, hospitalizations, and self-reported recovery activities. Laboratory-confirmed urine drug screens will be used to verify buprenorphine adherence.

Pre-implementation (Treatment-as-Usual) Prior to implementing the low-threshold BUP model, SSPs will provide standard care, which includes referral to community MOUD providers for BUP treatment.

Post-implementation (Low-Threshold BUP Program) Once implementation begins, SSPs will offer onsite BUP treatment directly through trained prescribers and peer outreach workers. Clients identified as eligible and interested will receive a medical evaluation from a study clinician (SC), including assessment for contraindications, education on BUP use, and initiation via home induction or observed dosing as appropriate.

Follow-up visits will occur approximately every 4 weeks for 6 months and include focused psychosocial counseling, urine drug screening (when requested by the study clinician), and continued prescription management. Both in-person and telehealth models may be used to enhance accessibility. Participants may use any FDA-approved formulation of buprenorphine, including injectable long-acting formulations, based on shared decision-making between study clinician and participant.

Implementation Facilitation Strategy

To support successful and sustainable adoption of the low-threshold BUP model, the study's Lead Node (LN) will develop and deliver an Implementation Facilitation Package. This package will include:

Structured training for SSP staff and clinicians on low-threshold buprenorphine principles and program logistics.

Coaching on identifying a site champion, hiring or engaging a prescriber, and establishing clear protocols for medication management.

Ongoing facilitation meetings between the LN and SSP implementation teams (champion, prescriber, peer outreach worker) to troubleshoot challenges, monitor fidelity, and adapt workflows.

Tools for tracking and sustaining reach, fidelity, and acceptability over time.

Hypotheses and Analytical Approach

The central hypothesis is that embedding low-threshold buprenorphine treatment within SSPs will improve engagement and retention in MOUD compared to standard referral pathways. Analyses will use mixed-effects regression models accounting for site-level clustering and time effects. Effectiveness analyses will focus on 3-month retention as the primary outcome, with sensitivity analyses at 6 months. Cost-effectiveness analyses will use quality-adjusted life years (QALYs) as the main effectiveness measure.

Implementation analyses will use the Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to identify determinants, measure outcomes, and map facilitation processes. Qualitative interviews with staff and participants will complement quantitative metrics, offering a comprehensive understanding of how and why the intervention succeeds or encounters barriers.

Expected Impact

This study addresses a critical public health need by testing a scalable, community-driven model of OUD treatment. If the low-threshold SSP-based buprenorphine program is found to be effective and cost-efficient, the Implementation Facilitation Package developed through this study will serve as a replicable framework for dissemination to SSPs or other community-based settings nationwide. The findings have the potential to directly inform national strategies for expanding access to evidence-based treatment, reducing overdose deaths, and promoting patient-centered care.

Inclusion Criteria:

1. ≥ 18 years old;
2. Meet DSM-5 criteria for moderate or severe OUD;
3. Interest in receiving buprenorphine treatment;
4. Speaks English or Spanish;
5. Currently an SSP client at the time of enrollment;
6. Ability to provide informed consent.

Exclusion Criteria:

1. Current use of prescribed opioid agonist treatment, as assessed by self-report, at the time of enrollment;
2. Unstable mental health or medical condition that requires an immediate clinical evaluation or higher level of care;
3. Allergy to buprenorphine;
4. Currently detained in jail, prison, residential substance use treatment facility, or other overnight facility as required by court of law. or have pending legal action that could prevent participation on study activities.

De-identified demographic, clinical, laboratory, survey, qualitative data collected from case report forms (CRFs) will be preserved and shared.

The following data will be preserved but not shared as they may contain a large volume of personally identifiable information (PII): data derived from qualitative interviews, participant locator and other administrative forms. Likewise, data from all free-text and/or comments fields will not be shared due to the nature of the data and risk of exposing PI.

Scientific data will be processed and analyzed with Statistical Analysis System (SAS) software and shared in SAS and ASCII formats.

Datasets will be available when either (1) the primary outcome paper has been accepted for publication, (2) the data has been locked for more than 18 months, or (3) the grant concludes; whichever comes first. Datasets will remain accessible via the National Institute on Drug Abuse (NIDA) Data Share contingent on NIDA's continued support of the archive. To date, NIDA Data Share has not deleted any deposited data.

Access to the scientific data will be controlled via a registration agreement for data use on the NIDA Data Share Website. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the NIDA Data Share Agreement.