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

利用大数据模拟 DAT 目标试验，加强阿片类药物使用障碍临床管理的证据基础

• 批准号: 10368971
• 负责人: Bohdan Nosyk
• 金额: $ 49.17万
• 依托单位: SIMON FRASER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368971
• 关键词: AIDS/HIV problem; Accident and Emergency department; Adherence; Admission activity; American; Antiviral Agents; Big Data; Biometry; British Columbia; Canada; Caring; Case Mixes; Cessation of life; Chronic; Client; Clinical; Clinical Management; Communities; Complement; Consultations; Data; Data Science; Databases; Disease; Dose; Drug Controls; Drug Screening; Economics; Elements; Ensure; Epidemic; Epidemiology; Fentanyl; Florida; Geographic state; Guidelines; HIV Seropositivity; Health; Health system; Healthcare Systems; Hepatitis C virus; Hospitalization; Illicit Drugs; Imprisonment; Income; Individual; Influentials; International; International AIDS; Level of Evidence; Link; Measures; Medical; Medicine; Mental Health; Methadone; Methodology; Methods; Michigan; National Institute of Drug Abuse; New Jersey; Ohio; Outcome; Pain; Pennsylvania; Performance; Perinatal Care; Persons; Pharmaceutical Preparations; Physicians; Policy Maker; Population; Positioning Attribute; Probability; Protocols documentation; Province; Public Health; Recommendation; Recording of previous events; Records; Regimen; Relapse; Reporting; Research; Rhode Island; Safety; Series; Societies; Specific qualifier value; Standardization; Structural Models; Suboxone; Testing; Time; United States National Institutes of Health; United States Substance Abuse and Mental Health Services Administration; Update; Urine; Weight; West Virginia; Work; addiction; antiretroviral therapy; base; clinical practice; combat; comorbidity; comparative effectiveness; data sharing; design; evidence base; experience; flexibility; healing; health economics; high dimensionality; improved; mortality; opioid agonist therapy; opioid epidemic; opioid overdose; opioid use disorder; overdose death; patient subsets; public health emergency; response; screening; social structure; synergism; synthetic opioid; theories; therapy adherence; tool; treatment effect; uptake

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

摘要 DAT 18 -06 2016年，随着阿片类药物相关过量死亡人数的急剧增加， 加拿大哥伦比亚（BC省）宣布进入公共卫生紧急状态。BC在2018年报告了1，510例非法药物过量死亡， 每10万人中有31.0人，在美国各州中排名第10，与罗得岛（31.0）相当，仅次于西弗吉尼亚州（57.8）、俄亥俄州（46.3） 和宾夕法尼亚州（44.3），但领先于新泽西（30.0），密歇根州（27.8）和佛罗里达（25.1）。虽然四倍的增长 自2012年以来观察到的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，并经历了复发。 类阿片激动剂治疗是防治这一流行病的最有效手段之一。然而，OAT 在不列颠哥伦比亚省和国际上，吸收和保留的情况并不理想，主要受到社会和结构因素的影响，但也 偏离循证护理标准和零散护理，特别是对那些并发症。 此外，加拿大和美国阿片类药物使用障碍（OUD）管理临床指南的一些方面 是基于有限和低质量的证据。即使是现有治疗方法相对有效性的基本证据 在芬太尼时代，缺乏总体和关键人群的选择。 该提案旨在应用先进的因果推理方法，模拟三个国家的一系列“目标试验”， 近期目标：（1）确定美沙酮与丁丙诺啡/纳洛酮对不同的 接受OAT的患者亚组;（2）确定尿液药物筛查的影响-一种普遍存在的非证据- OUD护理的基本要素-OAT保留率和死亡率;以及（3）确定OAT对 阿片类药物使用障碍（PWOUD）合并肝炎患者对直接作用抗病毒药物的摄取和依从性 C病毒。“目标审判”框架通过反事实理论为比较效果提供了灵活的基础 治疗和临床管理策略的意向治疗或按方案的基础上。我们已经确定了一 与PWOUD临床管理相关的其他问题数量，其中指南得到较弱 经验证据，并将奋进回答尽可能多的这些问题，优先分析使用一个共同的 注重方法严谨性的框架，