Mondol Momenul Haque, Min Jeong Eun, Kurz Megan, Zanette Michelle, Hossain Md Belal, Bach Paxton, Gustafson Paul, Platt Robert W, Seaman Shaun, Socías Maria Eugenia, Nosyk Bohdan, Karim Mohammad Ehsanul
School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada.
Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada.
BMJ Open. 2025 Jul 22;15(7):e098318. doi: 10.1136/bmjopen-2024-098318.
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.
美沙酮和丁丙诺啡/纳洛酮是治疗阿片类物质使用障碍患者的有效药物；然而，每日服药中断情况很常见，会降低这些药物的疗效。尽管包括不列颠哥伦比亚省（BC）在内的北美大多数司法管辖区的临床指南都建议在治疗中断后进行不同程度的具体剂量调整，但支持这些建议的证据有限。我们旨在评估替代剂量调整策略对加拿大BC省后续与过量用药相关的急性护理就诊及阿片类激动剂治疗停药的相对有效性。
通过九个卫生行政数据库的关联，我们提议对2010年1月1日至2022年12月31日期间在BC省开始使用美沙酮或丁丙诺啡/纳洛酮的18岁及以上成年人进行一项基于人群的回顾性队列研究。我们将针对美沙酮中断1 - 3天、4天和5 - 14天以及丁丙诺啡/纳洛酮中断1 - 5天和6 - 14天指定平行的假设试验，即目标试验。在索引中断后，主要结局是与过量用药相关的急性护理就诊时间和治疗停药时间（中断持续>14天），全因急性护理就诊时间作为次要结局。将使用倾向评分和工具变量方法估计意向性治疗效果。一系列敏感性分析将评估我们结果的稳健性，包括队列和时间线限制、暴露和结局的替代定义以及替代估计策略。
该方案、队列创建和分析计划已被普罗维登斯医疗保健研究所和西蒙弗雷泽大学研究伦理办公室分类并批准为质量改进计划。所有数据均经过去识别处理，按照省级隐私法规安全存储和访问。结果将传播给当地倡导团体和决策者、国家和国际临床指南制定者，在国际会议上展示，并以电子和印刷形式发表在同行评审期刊上。
