BACKGROUND & AIMS:
:In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.
背景与目标:
: 在比较临床研究中,一个共同的目标是评估暴露或干预是否会影响感兴趣的结果。但是,同样重要的是要了解干预如何影响结果的机制。例如,如果术前贫血显示15% 增加术后并发症的风险,那么重要的是量化患者接受术中输血的影响程度。中介分析试图量化干预对结果的影响 (如果有的话) 通过预先指定的中介或 “机制” 变量 (即位于暴露与结果之间的因果途径上的变量) 进行多少。因此,暴露对结果的影响可以分为直接和间接或介导的影响。当两个条件为真时,要求调解: 暴露影响调解人,调解人 (针对暴露进行调整) 影响结果。了解干预如何影响结果可以验证或使一个人的原始假设无效,还可以促进进一步的研究以修改负责因素,从而改善患者的结果。我们讨论了调查中介的研究的正确设计和分析,包括区分中介变量和混杂变量的重要性,在暴露是慢性还是急性时识别潜在中介的挑战以及要求调解的要求。考虑了简单的设计,以及包含多个介体,多个结果和混合数据类型的设计。方法用国家外科质量改进项目 (NSQIP) 收集的数据进行说明,并在一篇同伴论文中使用,该论文评估了术前贫血状态对术后结果的影响。