Mediators, moderators, and modulators of causal effects in clinical trials--Dynamically Modified Outcomes (DYNAMO) in health-related quality of life
Mediators, moderators, and modulators of causal effects in clinical trials--Dynamically Modified Outcomes (DYNAMO) in health-related quality of life
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DOI：
10.1007/s11136-008-9439-x
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Moinpour, Carol
中科院分区：
文献类型：
--
作者：
Donaldson, Gary W.;Nakamura, Yoshio;Moinpour, Carol
随机干预有不止一种效果，对一种治疗也有不止一种反应。随机对照试验（RCT）预先指定结果的平均组差估计了可能不同的因果机制中治疗的平均因果效应。为了理解干预的综合影响，我们建议识别和分离干预的直接因果效应与中介、调节和调节（个体差异）不受控制变量的影响。相关结果和适度干预描述了两种常见机制，通过这种机制，治疗与不受控制变量的相互作用扩大或限定了从随机对照试验中得出的因果推论，表明治疗影响超出了传统平均差异所捕获的范围。相关结果是随机化后测量之间的关联。治疗干预可能影响关系结果，个体差异可能调节它们。在适度干预中，治疗对感兴趣的结果的影响取决于个人属性或随机化前不受控制的变量。对这两种机制的认识和测量可以极大地改善对临床试验结果的解释。动态修正结果（DYNAMO）的综合正式系统提供了临床试验中各种因果影响和相互作用的综合分析。
There is more than one effect of a randomized intervention, and more than one response to a treatment. The mean group difference in the pre-specified outcome of a randomized controlled trial (RCT) estimates the average causal effect of treatment across causal mechanisms that may be distinct. To understand the comprehensive impact of an intervention, we propose identifying and separating the direct causal effects of the intervention from mediating, moderating, and modulating (individual differences) influences of uncontrolled variables.Relational outcomes and moderated interventions describe two common mechanisms by which treatment interactions with uncontrolled variables expand or qualify the causal inferences to be drawn from an RCT, signifying treatment impact beyond that captured by conventional mean differences. Relational outcomes are associations between post-randomization measures. The treatment intervention may affect relational outcomes, and individual differences may modulate them. With moderated interventions, the effect of treatment on the outcome of interest depends on personal attributes or pre-randomization uncontrolled variables.Awareness and measurement of both types of mechanisms can greatly improve interpretation of the results of a clinical trial.The integrated formal system of Dynamically Modified Outcomes (DYNAMO) provides comprehensive analysis of the diverse causal influences and interactions operating in a clinical trial.