Jan Klimas
J. Klimas1, L. Gorfinkel2, M. Hamilton1, A. Adam1, W. Cullen3, E. Wood1,4. 1British Columbia Centre on Substance Use, Canada; 2Columbia University, United States; 3University College Dublin, Ireland; 4University of British Columbia, Canada
Background: To assess effects of randomization on retention in fixed-dose oral opioid agonist treatment (OAT) evaluated with observational study designs (OBS) compared with retention assessed in randomized trials (RCT).
Methods: We searched four electronic databases (EMBASE, Medline, Cochrane Central Register of Controlled Trials, CINAHL) and analyzed data from RCTs and non-randomized observational studies with fixed-doses for buprenorphine versus methadone. Retention was measured as both categorical and continuous variable in included studies. A random effects meta-analysis was used to produce a pooled estimate of the effect of randomization on retention in OAT.
Results: Among 7,603 studies reviewed, 10 RCTs and 3 observational studies met inclusion criteria (n = 4,414), and compared fixed-dose oral buprenorphine with methadone. Across all controlled studies, the average retention rate was highly variable (buprenorphine range 20.0%-82.5%, and methadone range 30.7%-83.8%). For length of time retained in study, we observed no significant difference in treatment retention for buprenorphine versus methadone in randomized studies (standardized mean difference = -0.07; 95% CI: -0.35 – 0.21, p = 0.69). For presence on the final study day, we also observed no significant difference between buprenorphine and methadone treatment retention in randomized (risk ratio [RR] = 0.89; 95% CI: 0.73 – 1.08, p = 0.24) and non-randomized (RR = 0.75; 95% CI: 0.36 – 1.58, p = 0.45) studies.
Conclusion: Meta-analysis of existing RCTs and observational studies suggests buprenorphine is as effective in retaining patients in treatment as methadone regardless of randomization. While methadone is effective for many patients, the low overall retention rates suggest further examination of methods to optimize OAT retention is necessary, including the use of alternative formulations (e.g., injectable or extended release) and flexible take-home dosing schedules.