DAT-Emulating target trials with big data to strengthen the evidence base for the clinical management of opioid use disorder

摘要 DAT18-06 2016 年，随着阿片类药物过量死亡人数急剧增加，英国省 加拿大哥伦比亚（BC）宣布进入公共卫生紧急状态。 BC 省报告 2018 年有 1,510 人因非法药物过量死亡，这一比率 每 10 万人中 31.0 人，在美国各州中排名第 10，与罗德岛州 (31.0) 持平，落后于西弗吉尼亚州 (57.8)、俄亥俄州 (46.3) 和宾夕法尼亚州（44.3），但领先于新泽西州（30.0）、密歇根州（27.8）和佛罗里达州（25.1）。虽然增长了四倍 自 2012 年以来观察到的服药过量死亡主要归因于芬太尼和其他合成阿片类药物的污染 在非法药物供应方面，许多死者过去曾寻求治疗，但病情复发。 阿片类药物激动剂治疗（OAT）是对抗这一流行病最有效的工具之一。然而，燕麦 在 BC 省和国际上，吸收率和保留率均未达到最佳状态，这主要受到社会和结构因素的影响，但也受到影响 偏离基于证据的护理标准和分散的护理，特别是对于那些患有并发疾病的患者。 此外，加拿大和美国阿片类药物使用障碍 (OUD) 管理临床指南的多个方面 基于有限且低质量的证据。甚至是现有治疗方法比较有效性的基本证据 总体而言，芬太尼时代缺乏针对关键人群的选择。 该提案旨在应用因果推理的尖端方法来模拟三个领域的一系列“目标试验” 近期目标：(1) 确定美沙酮与丁丙诺啡/纳洛酮治疗不同疾病的疗效比较 接受 OAT 的患者亚组； (2) 确定尿液药物筛查的影响——一种普遍存在且无证据的—— OUD 护理的基础要素——OAT 保留率和死亡率； (3) 确定 OAT 对 阿片类药物使用障碍 (PWOUD) 并发肝炎患者对定向作用抗病毒药物的摄取和依从性 C病毒。 “目标试验”框架引导反事实理论为比较效果提供灵活的基础 基于意向治疗或按方案的治疗和临床管理策略。我们已经确定了一个 与 PWOUD 临床管理相关的其他问题的数量，其中指南得到较弱的支持 经验证据，并将努力回答尽可能多的问题，优先使用共同的分析 框架侧重于方法的严谨性和

ABSTRACT DAT18-06 In 2016, following a dramatic increase in opioid-related overdose deaths, the province of British Columbia (BC), Canada declared a public health emergency. BC reported 1,510 illicit drug overdose deaths in 2018, a rate of 31.0 per 100,000, placing it 10th among US states, equal to Rhode Island (31.0), behind West Virginia (57.8), Ohio (46.3) and Pennsylvania (44.3) but ahead of New Jersey (30.0), Michigan (27.8) and Florida (25.1). While the four-fold increase in overdose deaths observed since 2012 is largely attributable to the contamination of fentanyl and other synthetic opioids in the illicit drug supply, many decedents had sought treatment in the past and experienced relapses. Opioid agonist treatment (OAT) is among the most effective tools available to combat the epidemic. However, OAT uptake and retention is sub-optimal in BC and internationally, compromised largely by social and structural factors but also deviations from evidence-based standards of care and fragmented care, particularly for those with concurrent disorders. Furthermore, a number of aspects of Canadian and US clinical guidelines for the management of opioid use disorder (OUD) are based on limited and low-quality evidence. Even basic evidence on the comparative effectiveness of available treatment options overall and for key populations in the fentanyl era is lacking. This proposal aims to apply cutting-edge methods for causal inference in emulating a series of ‘target trials’ in three immediate aims: (1) to determine the comparative effectiveness of methadone versus buprenorphine/naloxone for different patient subgroups presenting for OAT; (2) to determine the impact of urine drug screening – a ubiquitous and non-evidence- based element of OUD care – on OAT retention and mortality; and (3) to determine the complementary effects of OAT on uptake and adherence to directing-acting antivirals for people with opioid use disorder (PWOUD) with concurrent Hepatitis C Virus. The ‘target trial’ framework channels counterfactual theory in providing a flexible basis for comparing the effects of treatment and clinical management strategies on either an intent-to-treat or per-protocol basis. We have identified a number of additional questions related to the clinical management of PWOUD where guidelines are supported by weaker empirical evidence and will endeavor to answer as many of these questions as possible, prioritizing analysis using a common framework focused on methodological rigor and