Drinking levels (binge, volume) and alcohol consequences: using national data to identify clinical trial endpoints

饮酒水平（酗酒、饮酒量）和酒精后果：使用国家数据确定临床试验终点

• 批准号: 9440313
• 负责人: DEBORAH S HASIN
• 金额: $ 18万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-10 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9440313
• 关键词: Abstinence; Academia; Address; Adopted; Adult; Age; Age of Onset; Alcohols; Anxiety; Characteristics; Clinical; Clinical Trials; Comorbidity; Data; Development; Diagnosis; Drug Use Disorder; Eligibility Determination; Epidemiology; Ethanol; Ethnic Origin; European; European Union; Extramural Activities; Frequencies; Gender; General Population; Goals; Gold; Grain; Guidelines; Heavy Drinking; Impairment; Industry; Measures; Medical; Medicine; Mental disorders; Methodology; Methods; Moods; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Occupational; Outcome; Outcome Measure; Participant; Pharmaceutical Preparations; Positioning Attribute; Public Health; Race; Randomized Clinical Trials; Randomized Controlled Trials; Recording of previous events; Research; Research Personnel; Risk; Sample Size; Services; Surveys; Treatment Efficacy; Treatment outcome; Uncertainty; United States Food and Drug Administration; Woman; World Health Organization; alcohol abuse therapy; alcohol consequences; alcohol use disorder; alcoholism therapy; clinically relevant; drinking; effective therapy; evidence base; experience; follow-up; high risk; improved; interest; men; mortality; optimal treatments; secondary analysis; success; treatment duration

Project Summary Randomized controlled trials, the gold standard in evaluating treatments for alcohol use disorders (AUDs), use drinking-reduction endpoints as the main outcomes. However, considerable uncertainty exists about how best to define drinking-reduction outcomes. Although clinicians and the Food and Drug Administration (FDA) long considered total abstinence as the best indicator of treatment efficacy, this is now seen as an overly restrictive outcome. The FDA presently focuses on the proportion of subjects with no Heavy-Drinking Days (HDD ≥5 drinks, or ≥5 for men, ≥4 for women) during a defined treatment period to define treatment efficacy. Another measure, Average Daily Volume (ADV; mean ETOH gm/day) developed by the World Health Organization (WHO) to define drinking levels for research purposes, has been adopted by the European Medicines Agency (EMA, the EU equivalent of the FDA), to define treatment success. However, because the evidence base for both HOD and ADV as clinical trial outcomes has many serious limitations, drinking outcome measures are considered a key methodological barrier to progress in developing more effective alcohol treatments. Empirical support for a drinking outcome's utility consists of its relationship to clinically relevant consequences, including interpersonal and occupational functioning, medical status, and alcohol use disorders. To examine empirical support for varying definitions of HOD, ADV and other drinking outcomes, the large, representative NESARC surveys (National Epidemiologic Survey on Alcohol and Related Conditions) offer important advantages, including richness and consistency of drinking and consequence measures. For this study, we will utilize data from NESARC Wave 1 (2001-2002; N=43,093) and Wave 2 (3-year follow-ups of Wave 1 participants, N=34,653) and NESARC-111 (2012-2013; N=36,318 new participants). We will use regression splines to determine the most informative functional relationships between HOD, ADV and consequences and identify key change-points in these relationships, to address the following key questions: (1) What levels of HOD and ADV are associated with higher risk of consequences? (2) What level of change in HOD and ADV over 3 years predicts change in consequences over the same period? (3) Are these associations modified by alcohol diagnoses and other alcohol characteristics (potential clinical trial eligibility, treatment history, early heavy drinking)? (4) Do these relationships differ between young and other adults (18-25 vs. 26+), by gender, race/ethnicity, or psychiatric comorbidity? We will also explore the following: Do alternative definitions of HOD and ADV influence findings? Does HOD or ADV offer advantages as outcomes? How do consequences relate to other common clinical trial outcomes: % days abstinent; mean drinks per drinking day? Study findings will help to define the relationship of different potential drinking outcome measures to consequences. The study is positioned to have a substantial impact on alcoholism treatment research by improving the ability to identify effective treatments for alcohol use disorders by defining the most clinically meaningful outcome measures.

项目概要 随机对照试验是评估酒精使用障碍 (AUD) 治疗的黄金标准，使用减少饮酒终点作为主要结果，然而，对于如何最好地定义饮酒减少结果，FDA (FDA) 长期以来一直认为存在很大的不确定性。戒酒是治疗效果的最佳指标，但现在这被视为过于严格的结果，FDA 目前关注的是没有酗酒日（HDD ≥ 5 次饮酒，或）的受试者比例。在规定的治疗期内，男性≥5，女性≥4），以确定治疗效果。世界卫生组织 (WHO) 制定了另一种衡量标准，即平均每日饮用量（ADV；平均 ETOH 克/天），用于定义研究饮酒水平。目的，已被欧洲药品管理局（EMA，相当于 FDA 的欧盟）采用来定义治疗成功。然而，由于 HOD 和 ADV 作为临床试验结果的证据基础有许多严重的局限性，因此饮酒结果衡量标准是不可行的。被认为是进展的关键方法障碍开发更有效的酒精治疗方法。对饮酒结果效用的实证支持包括其与临床相关后果的关系，包括人际关系和职业功能、医疗状况和酒精使用障碍。检查对 HOD、ADV 和其他饮酒的不同定义的实证支持。就结果而言，大型、有代表性的 NESARC 调查（全国酒精及相关疾病流行病学调查）具有重要优势，包括饮酒的丰富性和一致性以及后果测量。在本研究中，我们将利用 NESARC 第 1 波的数据。 （2001-2002 年；N=43,093）和第 2 波（第 1 波参与者的 3 年随访，N=34,653）和 NESARC-111（2012-2013 年；N=36,318 个新参与者）我们将使用回归样条来确定 HOD、ADV 和后果之间信息最丰富的功能关系，并确定这些关系中的关键变化点，以解决以下关键问题： (1) 什么水平的 HOD 和 ADV 与较高的后果风险相关？ (2) 3 年内 HOD 和 ADV 的变化程度可以预测同期后果的变化？ (3) 这些关联是否会因酒精诊断而改变？ (4) 年轻人和其他成年人（18-25 岁与 26 岁以上）之间的这些关系在性别、种族/民族或精神方面是否有所不同？我们还将探讨以下问题：HOD 和 ADV 的不同定义是否会影响研究结果？研究结果将有助于确定不同潜在饮酒结果指标与后果之间的关系，通过定义最具临床意义的结果指标，提高确定酒精使用障碍有效治疗方法的能力，从而对酗酒治疗研究产生重大影响。