Design and analysis of trials of combination therapies
Design and analysis of trials of combination therapies
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DOI：
10.15288/jsas.2005.s15.34
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发表时间：
2005-07-01
期刊：
影响因子：
--
通讯作者：
Anton, RF
中科院分区：
文献类型：
--
作者：
Hosking, JD;Cisler, RA;Anton, RF
目的：联合治疗可以有显着的优势，单药治疗。治疗的组合可以提供对功效的累加（或甚至协同）效应。它们可以允许使用较低剂量的每种组分以达到给定的功效水平，改善耐受性并减少不良反应。多组分治疗可以促进根据个体患者的需要定制治疗（例如，无应答者的治疗增强）。这些特征在开发酒精滥用和依赖的治疗策略方面似乎非常有吸引力，因为现有的单一疗法充其量表现出适度的疗效。方法：然而，联合治疗的试验在设计、执行和解释方面存在挑战，包括：（1）待比较的治疗组合的选择;（2）主要和次要假设的定义;（3）治疗持续时间、从治疗开始到对结果产生可观察影响的时间间隔和疗效评估间隔的干预措施之间的差异;（4）研究功效/样本量;（5）治疗递送的后勤、掩蔽和结果评估;和（6）不良事件的归因。结果如下：这些问题大多出现在联合收割机项目中，该项目是一系列旨在探索使用行为和药理学方法组合治疗酒精依赖的试验。将描述联合收割机试验上述挑战的解决方案和影响。结论：联合治疗的试验解决了许多重要的临床问题;然而，其复杂程度需要相当多的深谋远虑，试点调查和组织。
Objective: Combination therapies can have significant advantages over monotherapies. Combinations of therapies can provide additive (or even synergistic) effects on efficacy. They may permit use of lower doses of each component to achieve a given level of efficacy, improving tolerability and reducing adverse effects. A multicomponent treatment may facilitate tailoring of therapy to the needs of individual patients (e.g., treatment augmentation in nonresponders). These characteristics seem highly attractive in developing treatment strategies for alcohol abuse and dependence, because existing monotherapies have shown modest efficacy, at best. Method: However, trials of combination therapies present challenges in design, execution and interpretation, including: (1) choice of the treatment combinations to be compared; (2) definition of primary and secondary hypotheses; (3) differences between interventions in the duration of treatment, the time lag from the start of treatment to an observable effect on outcomes and interval for assessment of efficacy; (4) study power/sample size; (5) logistics of treatment delivery, masking and outcome assessment; and (6) attribution of adverse events. Results: Most of these issues arose in the COMBINE project, a sequence of trials intended to explore the use of combinations of behavioral and pharmacological approaches in the treatment of alcohol dependence. The resolution and impact of the challenges above for the COMBINE trial will be described. Conclusions: Trials of combination therapies address many important clinical questions; however, their level of complexity requires considerable forethought, pilot investigations and organization.