Piske Micah, Thomson Trevor, Krebs Emanuel, Hongdilokkul Natt, Bruneau Julie, Greenland Sander, Gustafson Paul, Karim M Ehsan, McCandless Lawrence C, Maclure Malcolm, Platt Robert W, Siebert Uwe, Socías M Eugenia, Tsui Judith I, Wood Evan, Nosyk Bohdan
Epidemiology and Population Health Program, BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
Centre hospitalier de l'Université de Montréal, CRCHUM, Montreal, Quebec, Canada.
BMJ Open. 2020 Sep 9;10(9):e036102. doi: 10.1136/bmjopen-2019-036102.
Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics.
We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity.
The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.
尽管最近有一项荟萃分析纳入了31项比较美沙酮和丁丙诺啡用于治疗阿片类药物使用障碍的随机对照试验，但在不同治疗方式对个体的长期有效性方面仍存在重要的知识空白，包括关于留存率和其他治疗结果的严格收集数据。来自真实世界数据的证据为改善针对弱势群体的个性化治疗和以患者为中心的指南以及为减少阿片类药物相关死亡率的策略提供了宝贵机会。我们的目标是在基于办公室的实践和专科诊所同时提供这两种药物的环境中，确定美沙酮与丁丙诺啡/纳洛酮在总体上以及在关键人群中的比较有效性。
我们提议对2008年1月1日至2018年9月30日期间居住在不列颠哥伦比亚省接受美沙酮或丁丙诺啡/纳洛酮阿片类激动剂治疗（OAT）的所有成年人进行一项回顾性队列研究。该研究将利用七个相互关联的人群层面行政数据库。主要结局包括在OAT中的留存率和全因死亡率。我们将使用意向性分析和符合方案分析来确定丁丙诺啡/纳洛酮与美沙酮的有效性——前者模拟灵活剂量试验，后者侧重于比较以最佳剂量提供的两种药物治疗方案。敏感性分析将用于评估结果对患者人群异质性和内部效度威胁的稳健性。
该方案、队列创建和分析计划已获批准，并被归类为一项免于伦理审查的质量改进举措（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）。计划通过会议和出版物，以及通过与发布临床指南的实体（如专业医学协会和公共卫生组织）直接接触和合作来进行传播。
