1 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, USA.
2 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, USA.
Stat Methods Med Res. 2018 Oct;27(10):3010-3025. doi: 10.1177/0962280217690414. Epub 2017 Jan 30.
A mediation model explores the direct and indirect effects of an initial variable ( X) on an outcome variable ( Y) by including a mediator ( M). In many realistic scenarios, investigators observe censored data instead of the complete data. Current research in mediation analysis for censored data focuses mainly on censored outcomes, but not censored mediators. In this study, we proposed a strategy based on the accelerated failure time model and a multiple imputation approach. We adapted a measure of the indirect effect for the mediation model with a censored mediator, which can assess the indirect effect at both the group and individual levels. Based on simulation, we established the bias in the estimations of different paths (i.e. the effects of X on M [ a], of M on Y [ b] and of X on Y given mediator M [ c']) and indirect effects when analyzing the data using the existing approaches, including a naïve approach implemented in software such as Mplus, complete-case analysis, and the Tobit mediation model. We conducted simulation studies to investigate the performance of the proposed strategy compared to that of the existing approaches. The proposed strategy accurately estimates the coefficients of different paths, indirect effects and percentages of the total effects mediated. We applied these mediation approaches to the study of SNPs, age at menopause and fasting glucose levels. Our results indicate that there is no indirect effect of association between SNPs and fasting glucose level that is mediated through the age at menopause.
中介模型通过包含中介变量 (M) 来探索初始变量 (X) 对结果变量 (Y) 的直接和间接影响。在许多实际情况下,研究人员观察到的是删失数据,而不是完整数据。目前针对删失数据的中介分析研究主要集中在删失结果上,而不是删失中介变量。在这项研究中,我们提出了一种基于加速失效时间模型和多重插补方法的策略。我们针对存在删失中介变量的中介模型,提出了一种中介效应的度量方法,该方法可以在群组和个体水平上评估间接效应。基于模拟,我们建立了使用现有方法(包括 Mplus 等软件中的简单方法、完全案例分析和 Tobit 中介模型)分析数据时,不同路径(即 X 对 M 的效应 [a]、M 对 Y 的效应 [b] 以及给定中介变量 M 时 X 对 Y 的效应 [c'])和间接效应估计的偏差。我们进行了模拟研究,以比较所提出的策略与现有方法的性能。与现有方法相比,所提出的策略能够准确估计不同路径、间接效应和总效应中介部分的系数。我们将这些中介方法应用于 SNP、绝经年龄和空腹血糖水平的研究。结果表明,SNP 与空腹血糖水平之间的关联没有通过绝经年龄介导的间接效应。
Stat Methods Med Res. 2017-1-30
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