Lai En-Yu, Shih Stephannie, Huang Yen-Tsung, Wang Shunping
Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island.
Stat Med. 2020 May 15;39(10):1415-1428. doi: 10.1002/sim.8485. Epub 2020 Feb 19.
Mediation analyses can help us to understand the biological mechanism in which an exposure or treatment affects an outcome. Single mediator analyses have been used in various applications, but may not be appropriate for analyzing intricate mechanisms involving multiple mediators that affect each other. Thus, in this article, we studied multiple sequentially ordered mediators for a dichotomous outcome and presented the identifiability assumptions for the path-specific effects on the outcome, that is, the effect of an exposure on the outcome mediated by a specific set of mediators. We proposed a closed-form estimator for the path-specific effects by modeling the dichotomous outcome using a probit model. Asymptotic variance of the proposed estimator is derived and can be approximated via delta method or bootstrapping. Simulations under a finite sample showed the validity of our method in capturing the path-specific effects when the probability of each potential counterfactual outcome is not small and demonstrated the utility of a computationally efficient alternative to bootstrapping for calculating variance. The method is applied to investigate the effects of polycystic ovarian syndrome on live birth rates mediated by estradiol levels and the number of oocytes retrieved in a large electronic in vitro fertilization database. We implemented the method into an R package SOMM, which is available at https://github.com/roqe/SOMM.
中介分析有助于我们理解暴露因素或治疗措施影响结局的生物学机制。单中介分析已在各种应用中使用，但可能不适用于分析涉及多个相互影响的中介因素的复杂机制。因此，在本文中，我们研究了针对二分结局的多个顺序排列的中介因素，并提出了对结局的路径特定效应的可识别性假设，即由特定中介因素集介导的暴露因素对结局的效应。我们通过使用概率单位模型对二分结局进行建模，提出了一种用于路径特定效应的闭式估计器。推导了所提估计器的渐近方差，并可通过德尔塔方法或自助法进行近似。有限样本下的模拟表明，当每个潜在反事实结局的概率不小的时候，我们的方法在捕捉路径特定效应方面是有效的，并且证明了一种计算效率高的替代自助法来计算方差的实用性。该方法应用于在一个大型电子体外受精数据库中研究多囊卵巢综合征通过雌二醇水平和获取的卵母细胞数量介导对活产率的影响。我们将该方法实现为一个R包SOMM，可在https://github.com/roqe/SOMM获取。
