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Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the effect through a mediator and the effect through all other pathways. When the mediator is a biomarker,…

Methodology · Statistics 2021-08-02 Ariel Chernofsky , Ronald J. Bosch , Judith J. Lok

We demonstrate a comprehensive semiparametric approach to causal mediation analysis, addressing the complexities inherent in settings with longitudinal and continuous treatments, confounders, and mediators. Our methodology utilizes a…

Although the exposure can be randomly assigned in studies of mediation effects, any form of direct intervention on the mediator is often infeasible. As a result, unmeasured mediator-outcome confounding can seldom be ruled out. We propose…

Methodology · Statistics 2021-09-30 BaoLuo Sun , Ting Ye

Causal mediation analysis can improve understanding of the mechanisms underlying epidemiologic associations. However, the utility of natural direct and indirect effect estimation has been limited by the assumption of no confounder of the…

Applications · Statistics 2020-06-16 Kara E. Rudolph , Oleg Sofrygin , Wenjing Zheng , Mark J. van der Laan

An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment…

Methodology · Statistics 2016-01-15 K. C. G. Chan , K. Imai , S. C. P. Yam , Z. Zhang

Causal mediation analysis provides techniques for defining and estimating effects that may be endowed with mechanistic interpretations. With many scientific investigations seeking to address mechanistic questions, causal direct and indirect…

Mediation analysis breaks down the causal effect of a treatment on an outcome into an indirect effect, acting through a third group of variables called mediators, and a direct effect, operating through other mechanisms. Mediation analysis…

Applications · Statistics 2025-05-13 Judith Abécassis , Houssam Zenati , Sami Boumaïza , Julie Josse , Bertrand Thirion

Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary treatments and static interventions, and (ii) direct and indirect effect decompositions have been pursued…

Methodology · Statistics 2022-01-13 Nima S. Hejazi , Kara E. Rudolph , Mark J. van der Laan , Iván Díaz

Causal mediation analysis has become an important and increasingly used framework for evaluating candidate immune response biomarkers in vaccine research. A controlled effects approach has been proposed to estimate controlled risk curves…

Methodology · Statistics 2026-04-09 Qijia He , Bo Zhang

While estimation of the marginal (total) causal effect of a point exposure on an outcome is arguably the most common objective of experimental and observational studies in the health and social sciences, in recent years, investigators have…

Statistics Theory · Mathematics 2012-10-18 Eric J. Tchetgen Tchetgen , Ilya Shpitser

We propose a semiparametric framework for causal inference with right-censored survival outcomes and many weak invalid instruments, motivated by Mendelian randomization in biobank studies where classical methods may fail. We adopt an…

Methodology · Statistics 2025-10-06 Qiushi Bu , Wen Su , Xingqiu Zhao , Zhonghua Liu

We propose semi- and non-parametric methods to estimate conditional interventional effects in the setting of two discrete mediators whose causal ordering is unknown. Average interventional indirect effects have been shown to decompose an…

Methodology · Statistics 2023-04-19 Max Rubinstein , Zach Branson , Edward H. Kennedy

Causal mediation analysis in cluster-randomized trials (CRTs) is complicated by the presence of multiple mediators, intracluster correlation, and within-cluster interference. Existing mediation methods often fall short in accommodating…

Methodology · Statistics 2026-04-14 Jiaqi Tong , Chao Cheng , Fan Li

In cluster-randomized trials (CRTs), there is emerging interest in exploring the causal mechanism in which a cluster-level treatment affects the outcome through an intermediate outcome. The majority of existing causal mediation methods are…

Methodology · Statistics 2026-01-12 Chao Cheng , Fan Li

In a unified framework, we provide estimators and confidence bands for a variety of treatment effects when the outcome of interest, typically a duration, is subjected to right censoring. Our methodology accommodates average, distributional,…

Methodology · Statistics 2017-10-04 Pedro H. C. Sant'Anna

Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated…

Methodology · Statistics 2017-01-11 Isabel R. Fulcher , Eric Tchetgen Tchetgen , Paige L. Williams

Causal mediation analysis decomposes the total effect of a treatment on an outcome into the indirect effect, operating through the mediator, and the direct effect, operating through other pathways. One can estimate only the pure indirect…

Applications · Statistics 2025-07-16 Vindyani Herath , Ronald J. Bosch , Judith J. Lok

Natural experiments are a cornerstone of applied economics, providing settings for estimating causal effects with a compelling argument for treatment randomisation, but give little indication of the mechanisms behind causal effects. Causal…

Econometrics · Economics 2025-10-07 Senan Hogan-Hennessy

The goal of causal mediation analysis, often described within the potential outcomes framework, is to decompose the effect of an exposure on an outcome of interest along different causal pathways. Using the assumption of sequential…

Methodology · Statistics 2021-11-09 Lexi Rene , Antonio R. Linero , Elizabeth Slate

Understanding causal mechanisms is crucial for explaining and generalizing empirical phenomena. Causal mediation analysis offers statistical techniques to quantify the mediation effects. Although numerous methods have been developed for…

Methodology · Statistics 2026-05-12 Jiawei Fu
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