Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined.

To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials.

This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024.

Combined race and ethnicity as self-classified by the patient at trial enrollment.

The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups.

A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients.

In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.