Estimation of Controlled Direct Effects in Longitudinal Mediation Analyses with Latent Variables in Randomized Studies

In a randomized study with longitudinal data on a mediator and outcome, estimating the direct effect of treatment on the outcome at a particular time requires adjusting for confounding of the association between the outcome and all preceding instances of the mediator. When the confounders are themselves affected by treatment, standard regression adjustment is prone to severe bias. In contrast, G-estimation requires less stringent assumptions than path analysis using SEM to unbiasedly estimate the direct effect even in linear settings. In this article, we propose a G-estimation method to estimate the controlled direct effect of treatment on the outcome, by adapting existing G-estimation methods for time-varying treatments without mediators. The proposed method can accommodate continuous and noncontinuous mediators, and requires no models for the confounders. Unbiased estimation only requires correctly specifying a mean model for either the mediator or the outcome. The method is further extended to settings where the mediator or outcome, or both, are latent, and generalizes existing methods for single measurement occasions of the mediator and outcome to longitudinal data on the mediator and outcome. The methods are utilized to assess the effects of an intervention on physical activity that is possibly mediated by motivation to exercise in a randomized study.

在一项包含中介变量（mediator）与结局变量（outcome）纵向数据的随机试验中，若要估计干预（treatment）对某一特定时间点结局的直接效应，需要校正结局与所有此前出现的中介变量之间关联的混杂（confounding）。当混杂因素（confounders）本身受到干预影响时，标准回归校正方法极易产生严重偏倚。与之相对，即便在线性场景下，G估计（G-estimation）相较于使用结构方程模型（SEM，Structural Equation Modeling）的路径分析，所需假设更宽松，却可无偏估计直接效应。本文提出一种G估计方法，用于估计干预对结局的控制直接效应（controlled direct effect），该方法适配了现有针对无中介变量的时变干预（time-varying treatments）的G估计框架。所提方法可兼容连续型与非连续型中介变量，且无需为混杂因素构建模型。仅需正确设定中介变量或结局的均值模型，即可实现无偏估计。本方法进一步拓展至中介变量、结局或二者均为潜变量（latent variable）的场景，并将现有针对中介与结局单次测量的方法推广至二者的纵向数据场景。本研究利用所提方法，在一项随机试验中评估了一项干预对身体活动的效应，该效应可能通过锻炼动机介导。