Comparative effectiveness of take-home dosing schedules for opioid agonist treatment in British Columbia, Canada: A target trial emulation protocol using a population-based observational study

Abstract

Introduction The introduction of fentanyl and its analogues in the illicit drug supply has prompted greater emphasis on refining clinical treatment protocols to ensure sustained retention in opioid agonist treatment (OAT). Take-home dosing may lessen the treatment burden on clients and thus reduce the risk of treatment discontinuation. The evidence base supporting the use of take-home dosing, including the optimal duration of dispensations, is however limited. The objective of this study is to determine the comparative effectiveness of alternative take-home dosing schedules, as observed in clinical practice in British Columbia, Canada from 2010-2022. Methods and analysis We propose to emulate a target trial with a population-level retrospective study of individuals initiating methadone or buprenorphine/naloxone between 01/01/2010-12/31/2022 who are 18 years of age or older and not currently incarcerated or pregnant with no history of cancer or palliative care. Our study will draw on nine linked health administrative databases from British Columbia and will evaluate take-home doses of 2-5 days, 6 days or >6 days compared to continuous daily dosing. The primary outcomes include OAT discontinuation and all-cause mortality on treatment. A causal per-protocol analysis is proposed with longitudinal matching and inverse probability of censoring weighting approaches to adjust for time-fixed and time-varying confounding. A range of sensitivity analyses will be executed to determine the robustness of results.