Comparative effectiveness of methadone take-home dose initiation in British Columbia, Canada: protocol for a population-based retrospective cohort study using target trial guidelines.

INTRODUCTION: Due to inferior safety profile and higher risk of diversion than buprenorphine/naloxone, guidelines typically recommend stringent eligibility criteria such as daily witnessed ingestion of methadone for at least 12 weeks before considering take-home doses. Recent research has focused on whether or not to initiate take-home methadone doses, often using pandemic-era data when temporary prescribing changes provided a natural experiment on the impact of access to take-home doses. However, none of these studies adequately examined the optimal timing and criteria for safely starting take-home doses to enhance treatment outcomes. To determine the optimal timing for initiating methadone take-home doses, we will compare the effects of different initiation times on time to treatment discontinuation, all-cause mortality and acute-care visits among individuals who completed methadone induction in British Columbia, Canada, from 2010 to 2022. METHODS AND ANALYSIS: We propose emulating a target trial using linked population-level health administrative data for all individuals aged 18 or older living in British Columbia, Canada, completing methadone induction between 1 January 2010 and 31 December 2022. The exposure strategies will include no take-home dosing and take-home dose initiation in ≤4, 5-12, 13-24 and 25-52 weeks since completed induction. The outcomes will include the time to treatment discontinuation, all-cause mortality and acute-care visits. We propose a per-protocol analysis with a clone-censor-weighting approach to address the immortal time bias implicit in the comparison of alternative take-home dose initiation times. Subgroup and sensitivity analyses, including cohort restrictions, study timeline variations, eligibility criteria modifications and outcome reclassifications, are proposed to assess the robustness of our results. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals.