Département de Médecine Sociale et Préventive, Université Laval, Québec City, Québec, Canada.
Axe santé des Populations et Pratiques Optimales en Santé, Centre de Recherche du CHU de Québec - Université Laval, Québec City, Québec, Canada.
Stat Med. 2021 May 10;40(10):2339-2354. doi: 10.1002/sim.8906. Epub 2021 Mar 1.
It is now well established that adjusting for pure predictors of the outcome, in addition to confounders, allows unbiased estimation of the total exposure effect on an outcome with generally reduced standard errors (SEs). However, no analogous results have been derived for mediation analysis. Considering the simplest linear regression setting and the ordinary least square estimator, we obtained theoretical results showing that adjusting for pure predictors of the outcome, in addition to confounders, allows unbiased estimation of the natural indirect effect (NIE) and the natural direct effect (NDE) on the difference scale with reduced SEs. Adjusting for pure predictors of the mediator increases the SE of the NDE's estimator, but may increase or decrease the variance of the NIE's estimator. Adjusting for pure predictors of the exposure increases the variance of estimators of the NIE and NDE. Simulation studies were used to confirm and extend these results to the case where the mediator or the outcome is binary. Additional simulations were conducted to explore scenarios featuring an exposure-mediator interaction as well as the relative risk and odds ratio scales for the case of binary mediator and outcome. Both a regression approach and an inverse probability weighting approach were considered in the simulation study. A real-data illustration employing data from the Canadian Study of Health and Aging is provided. This analysis is concerned with the mediating effect of vitamin D in the effect of physical activity on dementia and its results are overall consistent with the theoretical and empirical findings.
现在已经证实，除了混杂因素外，调整结局的纯预测因素还可以在一般情况下减少标准误（SE）的情况下，对暴露对结局的总效应进行无偏估计。然而，对于中介分析，还没有得出类似的结果。考虑最简单的线性回归设置和普通最小二乘估计量，我们得到了理论结果，表明除了混杂因素外，调整结局的纯预测因素还可以对差异尺度上的自然间接效应（NIE）和自然直接效应（NDE）进行无偏估计，并减少 SE。调整中介的纯预测因素会增加 NDE 估计量的 SE，但可能会增加或减少 NIE 估计量的方差。调整暴露的纯预测因素会增加 NIE 和 NDE 估计量的方差。模拟研究用于确认和扩展这些结果，以适用于中介或结局为二进制的情况。另外的模拟用于探索具有暴露-中介相互作用的情况，以及在中介和结局为二进制的情况下相对风险和优势比尺度。模拟研究中考虑了回归方法和逆概率加权方法。提供了一个使用加拿大健康老龄化研究数据的真实数据说明。该分析涉及维生素 D 在体力活动对痴呆症影响中的中介效应，其结果总体上与理论和经验发现一致。
