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 to 2022.

We propose to emulate a target trial with a population-level retrospective study of individuals initiating methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 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 with 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.

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 and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

Selecting an optimal initial dosage of opioid agonist treatment (OAT) balances effectiveness and safety, as initial doses that are too low may be insufficient, potentially prompting clients to seek unregulated drugs to alleviate withdrawal symptoms, which may increase the likelihood of treatment discontinuation. Conversely, initial doses that are too high carry a risk of overdose. As opioid tolerance levels have risen in the fentanyl era, linked population-level data capturing initial doses in the real world provide a valuable opportunity to refine existing guidance on optimal OAT dosing at treatment initiation. Our objective is to determine the comparative effectiveness of alternative initial doses of methadone, buprenorphine-naloxone and slow-release oral morphine at OAT initiation, as observed in clinical practice in British Columbia (BC), Canada.

We propose a population-level retrospective observational study with a linkage of nine provincial health administrative databases in BC, Canada (1 January 2010 to 31 December 2022). Our study includes two time-to-event primary outcomes: OAT discontinuation and all-cause mortality during follow-up. We propose ‘initiator’ target trial analyses for each medication using both propensity score weighting and instrumental variable analyses to compare the effect of different initial OAT doses on the hazard of time-to-OAT discontinuation and all-cause mortality. A range of sensitivity analyses will be used to assess the robustness of the results.

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 electronically and in print.

Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.

We propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.

This study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.

Opioid agonist treatment (OAT) prescribing patterns have shifted in recent years in British Columbia (BC), Canada due to the increasingly toxic unregulated drug supply. Experimental evidence to support guidelines on the effectiveness of maintaining clients at different maintenance dosage levels is incomplete and outdated for the fentanyl era. Our objective is to assess the risk of treatment discontinuation and mortality among individuals receiving different maintenance dosage strategies for OAT with methadone, buprenorphine/naloxone or slow-release oral morphine (SROM) at the population level in BC, Canada.

We propose a retrospective population-level study of BC residents initiating OAT on methadone, buprenorphine/naloxone or SROM between 1 January 2010 and 31 December 2022 who were ≥18 years of age with no known pregnancy, no history of cancer diagnosis or receiving palliative care and not currently incarcerated. Our study will employ health administrative databases linked at the individual level to emulate a target trial per OAT type where individuals will be assigned to discrete maintenance dosing strategies, according to the full range observed in BC during the study period. Primary outcomes include treatment discontinuation and all-cause mortality. To determine the effectiveness of alternative maintenance doses, we will emulate a ‘per-protocol’ trial using a clone-censor-weight approach to adjust for measured time-dependent confounding by indication.

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. All data are deidentified, securely stored and accessed in accordance with provincial privacy regulations. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

Methadone and buprenorphine/naloxone are effective medications for people with opioid use disorder; however, interruptions in daily dosing are common and diminish the benefits of these medications. While clinical guidelines in most North American jurisdictions, including British Columbia (BC), recommend dose adjustment after treatment interruptions to varying levels of specificity, the evidence to support these recommendations is limited. We aim to estimate the comparative effectiveness of alternative dose adjustment strategies on subsequent overdose-related acute care visits and discontinuation of opioid agonist treatment in BC, Canada.

Using a linkage of nine health administrative databases, we propose a population-level retrospective cohort study of adults aged 18 years or older in BC who initiated methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 2022. We will specify parallel hypothetical trials, known as target trials, for methadone interruptions of 1–3 days, 4 days and 5–14 days, and buprenorphine/naloxone interruptions of 1–5 days and 6–14 days. Following the index interruption, the primary outcomes are the time to overdose-related acute care visits and treatment discontinuation (interruptions lasting >14 days), with time to all-cause acute care visits as a secondary outcome. The intention-to-treat effect will be estimated using both propensity score and instrumental variable approaches. A range of sensitivity analyses will assess the robustness of our results, including cohort and timeline restriction, alternative definitions of exposure and outcome and alternative estimation strategies.

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics. All data are deidentified, securely stored and accessed in accordance with provincial privacy regulations. 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 electronically and in print.