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治疗的疗效的研究中，临床发现的某些异质性可以归因于广泛使用标准的统计分析工具的简易饮酒措施的标准统计分析工具，这些工具不良反映了饮酒数据的分布和复杂性。基于轨迹的新型统计分析工具随着时间的流逝提供了对饮酒行为影响以及治疗依从性和治疗反应的相互作用的更现实和完整的描述。迄今为止，合并的研究是最大的随机临床试验，旨在回答有关将行为和药理干预措施结合的好处的问题。它成功地证实了一些假设，但对其他主要疗效假设提供了令人沮丧的结果。进一步了解这项研究的阳性和负面结果，确定治疗有效治疗的受试者的亚组，并评估合规性对反应的影响对于将酒精研究领域推向改善疗法和基于个体的治疗至关重要。本文中，我们建议使用Nagin（1999）的基于轨迹的方法来评估联合研究中饮酒和依从性的变化模式。该研究招募了1,383名戒酒依赖的患者，并测试了纳曲酮，丙曲酸盐和联合行为干预（CBI）的疗效。对两个主要终点的分析，重量饮酒的第一天和戒酒百分比的时间表明，与MM +安慰剂相比，Naltrexone或CBI的结果改善了结果，但令人惊讶的是，Naltrexone + CBI的组合与单独的治疗和Acamprosation均不相比或CBINECONE或CBINECONE或CBINECONE均可产生更好的结果。基于轨迹的方法将允许参与者的饮酒行为和治疗依从性中的异质性表征，将阐明有关亚甲酸酯的一些负面发现以及纳曲酮和CBI的结合，并允许评估合规性，治疗和饮酒行为之间的相互作用。 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）探索停止治疗后饮酒的轨迹。这些分析的结果可能为使用药物和行为干预措施来治疗酒精成瘾的新理论和临床见解提供了新的理论和临床见解。