Comparing Outpatient Treatment Retention Among Individuals Using Fentanyl Randomized to Low-dose and Direct-to-inject Buprenorphine Initiation

Receiving continuous treatment with buprenorphine sublingual prescriptions or injections administrations during the 90 days of follow up post-randomization as intended-to-treat. A period without buprenorphine treatment ≥8 days will be considered treatment discontinuation. Number of days of continuous treatment with the site clinician prescribing sublingual or injectable buprenorphine treatment during the 90 days post-randomization among RCT participants

Patient-reported satisfaction with buprenorphine initiation protocol measured by Likert-scale satisfaction survey administered on day 7 follow-up visit

Similar to the primary intention to treat analysis, though we will be analyzing data and individuals based on actual protocol received and treated, rather than assigned treatment at randomization

Defined as successfully completing buprenorphine initiation. For LDI treatment arm, this means self-reported completion of initiation "blister pack" during Days 1-6 at clinical follow up and pick up of buprenorphine refill based on prescription data. For DTI, this means administration of initial weekly BRIXADI injection and subsequent monthly BRIXADI or SUBLOCADE buprenorphine injection within 7 days of the initial weekly injection.

Concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by urinary drug screen at day 7 follow-up visit.

Concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by urinary drug screen at day 30 follow-up visit.

Concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by urinary drug screen at day 90 follow-up visit.

Concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 7 follow-up visit.

Concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 30 follow-up visit.

Concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 90 follow-up visit.

Number of days of concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 7 follow-up visit.

Number of days of concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 30 follow-up visit.

Number of days of concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 90 follow-up visit.

At baseline, a Clinical Opioid Withdrawal Score (COWS) survey will be administered and confirmed with the prescribing clinician.

During each of the first 7 days, participants will rate the severity of withdrawal symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Subjective Opioid Withdrawal Scale [SOWS] (from 0-4, with 0 being not at all and 4 being extreme) to assess for subjective withdrawal symptoms to minimize participant burden while ensuring reliable data capture.

During each of the first 7 days, participants will rate the severity of withdrawal symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Subjective Opioid Withdrawal Scale [SOWS] (from 0-4, with 0 being not at all and 4 being extreme) to assess for subjective withdrawal symptoms to minimize participant burden while ensuring reliable data capture. We will calculate peak withdrawal symptoms during the 7-day period.

During each of the first 7 days, participants will rate the severity of craving symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Visual Analog Scale [VAS] (from 0-100, with 0 being none at all and 100 being strongest craving ever) to assess for subjective craving symptoms to minimize participant burden while ensuring reliable data capture.

During each of the first 7 days, participants will rate the severity of craving symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Visual Analog Scale [VAS] (from 0-100, with 0 being none at all and 100 being strongest craving ever) to assess for subjective craving symptoms to minimize participant burden while ensuring reliable data capture. We will calculate the peak craving severity during the first 7 days.

Number of adverse events within 30 days, coded by body system and MedDRA classification. All adverse events reported by participants or identified through clinical documentation will be recorded and categorized by severity, duration, and relationship to the study intervention.

Number of serious adverse events within 30 days, coded by body system and MedDRA classification. All adverse events reported by participants or identified through clinical documentation will be recorded and categorized by severity, duration, and relationship to the study intervention.

Number of emergency department visits and hospital admissions within 30 days, coded by body system and MedDRA classification. All adverse events reported by participants or identified through clinical documentation will be recorded and categorized by severity, duration, and relationship to the study intervention.

Documented deaths due to opioid overdose during the 90-day follow-up period will be identified through the EHR and, if available, linkage to external death records.

Study staff will track whether the assigned LDI or DTI protocol was delivered as intended, including any deviations from the dosing schedule or logistical challenges encountered