Trajectories of Drinking and Compliance in the COMBINE Study

COMBINE 研究中的饮酒轨迹和依从性

• 批准号: 7351733
• 负责人: Ralitza Gueorguieva
• 金额: $ 19.02万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7351733
• 关键词: Adherence; Alcohol dependence; Alcohols; Behavior Therapy; Behavioral; Class; Clinical; Cognitive Therapy; Combined Modality Therapy; Condition; Daily; Data; Data Aggregation; Data Analyses; Drug Exposure; Drug Formulations; End Point; Enrollment; European; Failure; Floor; Growth; Heavy Drinking; Heterogeneity; Individual; Intervention; Joints; Light; Measures; Medication Management; Modeling; Naltrexone; Negative Finding; Numbers; Outcome; Outcome Measure; Participant; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Placebo Effect; Placebos; Probability; Process; Randomized; Randomized Clinical Trials; Rate; Research; Sample Size; Sampling; Self Efficacy; Standards of Weights and Measures; Subgroup; Testing; Time; Withholding Treatment; Woman; acamprosate; alcohol research; analytical tool; base; compliance behavior; day; design; drinking; drinking behavior; follow-up; improved; insight; medication compliance; novel; novel strategies; response; tool; treatment duration; treatment effect

DESCRIPTION (provided by applicant): Some of the heterogeneity of clinical findings in studies evaluating the efficacy of pharmacotherapies and behavioral therapies in the treatment of alcohol dependence can be attributed to the wide use of standard statistical analytical tools of summary drinking measures that poorly reflect the distributions and complexity of drinking data. Novel statistical analysis tools based on trajectories over time provide a more realistic and complete picture of treatment effects on drinking behavior, and of the interplay of treatment compliance and treatment response. The COMBINE Study is the largest randomized clinical trial to date designed to answer questions about the benefits of combining behavioral and pharmacological interventions. It was successful in confirming some hypotheses but provided discouraging results on other primary efficacy hypotheses. Further understanding of both the positive and the negative results of this study, identifying subgroups of subjects for whom treatment is effective and assessing the effects of compliance on response are vital to moving the field of alcohol research forward towards improved therapies and individual-based treatments. Herein we propose to assess patterns of change over time in drinking and compliance in the COMBINE Study using the trajectory-based approach of Nagin (1999). The study enrolled 1,383 abstinent alcohol dependent patients and tested the efficacy of naltrexone, acamprosate, and Combined Behavioral Intervention (CBI). Analyses of the two primary endpoints, time to the first day of heavy drinking and percent days abstinent, revealed that either naltrexone or CBI improved outcomes compared to MM + placebo but surprisingly, the combination of naltrexone + CBI did not yield better outcomes than either treatment alone, and acamprosate was not efficacious either alone or in combination with naltrexone or CBI. The trajectorybased approach will allow characterization of the heterogeneity in participants' drinking behavior and treatment compliance, will shed light on some of the negative findings regarding acamprosate and the combination of naltrexone and CBI, and will allow assessment of the interplay between compliance, treatment and drinking behavior. Our specific aims are 1) to identify different trajectory classes of drinking over time and to assess medication and CBI main effects and interactions on the probability to follow particular trajectories, 2) to examine trajectories of drinking prior to randomization as potential moderators of naltrexone, acamprosate and CBI effects, 3) to examine trajectories of treatment participation (e.g., MM, CBI, and medication adherence) and their effects on treatment response, and 4) to explore trajectories of drinking following discontinuation of treatment. The results of these analyses may offer new theoretical and clinical insights into the use of medications and behavioral interventions for the treatment of alcohol addiction.

描述（由申请人提供）：在评估药物疗法和行为疗法治疗酒精依赖的功效的研究中，临床结果的一些异质性可归因于广泛使用总结饮酒措施的标准统计分析工具，这些工具不能很好地反映酒精依赖的情况。饮酒数据的分布和复杂性。基于随时间变化的轨迹的新型统计分析工具可以更真实、更完整地描述治疗对饮酒行为的影响，以及治疗依从性和治疗反应的相互作用。 COMBINE 研究是迄今为止规模最大的随机临床试验，旨在回答有关行为和药物干预相结合的益处的问题。它成功地证实了一些假设，但对其他主要功效假设提供了令人沮丧的结果。进一步了解这项研究的积极和消极结果，确定治疗有效的受试者亚组，并评估依从性对反应的影响，对于推动酒精研究领域朝着改进疗法和基于个体的治疗方向发展至关重要。在此，我们建议使用 Nagin（1999）基于轨迹的方法来评估 COMBINE 研究中饮酒和依从性随时间变化的模式。该研究招募了 1,383 名戒酒酒精依赖患者，并测试了纳曲酮、阿坎酸和联合行为干预 (CBI) 的疗效。对两个主要终点（即到酗酒第一天的时间和戒酒天数百分比）的分析表明，与 MM + 安慰剂相比，纳曲酮或 CBI 均改善了结果，但令人惊讶的是，纳曲酮 + CBI 的组合并没有比任何一种治疗产生更好的结果单独使用阿坎酸，无论是单独使用还是与纳曲酮或 CBI 联合使用均无效。基于轨迹的方法将允许描述参与者饮酒行为和治疗依从性的异质性，将揭示有关阿坎酸以及纳曲酮和 CBI 组合的一些负面发现，并将允许评估依从性、治疗和饮酒之间的相互作用行为。我们的具体目标是 1) 确定随时间推移的不同饮酒轨迹类别，并评估药物和 CBI 对遵循特定轨迹的概率的主要影响和相互作用，2) 在随机化之前检查饮酒轨迹作为纳曲酮、阿坎酸的潜在调节剂和 CBI 效果，3) 检查治疗参与轨迹（例如 MM、CBI 和药物依从性）及其对治疗反应的影响，4) 探索停止治疗后的饮酒轨迹。这些分析的结果可能为使用药物和行为干预治疗酒精成瘾提供新的理论和临床见解。