Optimal Endpoints in Clinical Trials of Cognitive Behavioral Interventions for AOD: An Aggregate and Individual Patient Data Meta-Analysis

项目摘要 本研究的目的是对认知理论进行全面的、最新的元分析 行为疗法、复发预防和其他认知-行为干预(CBIS)功效， 缓和的效果，以及调解过程。基于我们之前的工作(R21 AA026006；PI：Magill，Co-is： Kiluk&Ray；咨询公司：Carroll&Tonigan)，这个R01项目将从 之前的荟萃分析样本(即K~100项初步研究)将进行更新搜索，以得出所有最近的 试验，并将纳入先进的方法，如网络元分析(NMA)和个人 参与者数据荟萃分析(IPD)。在我们以前的工作中，消费频率和重频是一体的 早期和一个晚期随访时间点是感兴趣的先验指标。然而，关于什么的对话 构成随机临床试验的最佳终点近年来有所增长(例如，主动倡议)， 认为在禁欲或大量消费之外的一系列功能终点应该更有意义 强调治疗开发和临床结果研究。其他端点，如Related 问题、应对行为以及心理和一般健康肯定是患者、家人和 临床提供者。此外，这些指标已成为定义复苏的关键因素。 对R21 AA026006中审查的试验样本的初步分析表明，4%到50%的数据可能 每项研究都有端点可用，而且大约79%的可用数据尚未提供 收集、分析或报告。此外，使用R21 AA023662(PI：MAGILL)的方法，直接数据 将进行选择酒精使用障碍(AUD)研究的请求，以及一些相关的个人资料 已经同意满足这样的要求。在这种情况下，将使用两阶段IPD进行聚合 CBI过程的通径分析，考虑CBI疗效的可能机制。尽管R01级别的元分析 开展了以下项目：a)酒精药物疗法，b)酒后驾车干预，c)短暂干预 青少年/青壮年，以及d)将澳新病和创伤相关疗法结合起来，没有这样的项目 在CBIS上进行，这是尽管它们在酒精和其他直接患者护理方面的长寿和中心地位 药物使用障碍。提议的项目，从发布的报告中提取所有可用的端点， 具体进行AUD试验的数据请求，并进行NMA以说明类型的可变性 对比情况将为临床和方法学建议提供依据：1)CBI的实施和 交付，2)衡量CBI效果的最佳端点，以及3)在上下文中定义和了解恢复 以证据为基础的治疗。

Project Abstract The purpose of this study is to conduct a comprehensive and state-of-the-art meta-analysis of Cognitive Behavioral Therapy, Relapse Prevention, and other Cognitive-Behavioral Intervention (CBIs) efficacy, moderated efficacy, and mediating processes. Building upon our prior work (R21 AA026006; PI: Magill, Co-Is: Kiluk & Ray; Consultants: Carroll & Tonigan), this R01 project will extract additional functional endpoints from the prior meta-analytic sample (i.e., K~100 primary studies), will conduct an updated search to yield all recent trials, and will incorporate advanced methodologies such as Network Meta-Analysis (NMA) and Individual Participant Data Meta-Analysis (IPD). In our prior work, consumption frequency and heavy frequency at one early and one late follow-up time point were the a priori indicators of interest. However, the dialogue on what constitutes an optimal endpoint in randomized clinical trials has grown in recent years (e.g., ACTIVE Initiative), arguing that a range of functional endpoints beyond abstinence or heavy consumption should be of greater emphasis in treatment development and clinical outcome research. Alternative endpoints such as related problems, coping behaviors, and mental and general health are certainly of interest to patients, families, and clinical providers. These indicators have additionally become key constructs in the what defines recovery. Preliminary analyses of the sample of trials reviewed in R21 AA026006 show that data for 4 to 50 possible endpoints are available per study, and that approximately 79% of the available data have yet to be collected, analyzed, or reported. In addition, using the methods of R21 AA023662 (PI: Magill), direct data requests for a selection of alcohol use disorder (AUD) studies will be conducted, and a number of relevant PIs have already agreed to meet such requests. In this case, a two-stage IPD will be used to conduct an aggregate path analysis of CBI process, considering putative mechanisms of CBI efficacy. Although R01-level meta-analytic projects have been conducted on a) alcohol pharmacotherapies, b) DUI interventions, c) brief interventions for adolescents/young adults, and d) combined AUD and trauma-related therapies, no such project has been undertaken on CBIs, and this is despite their longevity and centrality in direct patient care for alcohol and other drug use disorders. The proposed project, extracting all available endpoints from the published reports, conducting data requests for AUD trials specifically, and conducting NMA to account for variability in type of contrast condition will inform clinical and methodological recommendations on: 1) CBI implementation and delivery, 2) optimal endpoints for measuring CBI effect, and 3) defining and understanding recovery in the context of evidence-based treatment.