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Cluster-randomized trials (CRTs) are widely used to evaluate group-level interventions and increasingly collect multiple outcomes capturing complementary dimensions of benefit and risk. Investigators often seek a single global summary of…

Methodology · Statistics 2026-01-22 Xinyuan Chen , Fan Li

In cluster-randomized trials, generalized linear mixed models and generalized estimating equations have conventionally been the default analytic methods for estimating the average treatment effect as routine practice. However, recent…

Methodology · Statistics 2025-09-19 Fan Li , Jiaqi Tong , Xi Fang , Chao Cheng , Brennan C. Kahan , Bingkai Wang

Causal mediation analysis is a powerful tool in environmental health research, allowing researchers to uncover the pathways through which exposures influence health outcomes. While traditional mediation methods have been widely applied to…

Cluster-randomized trials (CRTs) are widely used to evaluate interventions delivered at the clinic, practice, or community level. Although standard analyses typically target average treatment effects, such summaries mask potentially…

Methodology · Statistics 2026-04-16 Changjun Li , Xi Fang , Michael O. Harhay , Andrew B. Forbes , F. Perry Wilson , Guangyu Tong , Fan Li

Stepped wedge cluster randomized controlled trials are typically analyzed using models that assume the full effect of the treatment is achieved instantaneously. We provide an analytical framework for scenarios in which the treatment effect…

Methodology · Statistics 2025-09-25 Avi Kenny , Emily Voldal , Fan Xia , Patrick J. Heagerty , James P. Hughes

Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials (SW-CRTs). A key consideration for analyzing a SW-CRT is accounting for the potentially complex correlation structure, which can be achieved by…

Methodology · Statistics 2024-08-21 Yongdong Ouyang , Monica Taljaard , Andrew B Forbes , Fan Li

Many epidemiological questions concern potential interventions to alter the pathways presumed to mediate an association. For example, we consider a study that investigates the benefit of interventions in young adulthood for ameliorating the…

Methodology · Statistics 2020-07-14 Margarita Moreno-Betancur , Paul Moran , Denise Becker , George C Patton , John B Carlin

Recently, methodology was presented to facilitate the incorporation of interim analyses in stepped-wedge (SW) cluster randomised trials (CRTs). Here, we extend this previous discussion. We detail how the stopping boundaries, allocation…

Methodology · Statistics 2018-03-28 Michael Grayling , David Robertson , James Wason , Adrian Mander

Intensive longitudinal data, characterized by frequent measurements across numerous time points, are increasingly common due to advances in wearable devices and mobile health technologies. We consider evaluating causal mediation pathways…

Methodology · Statistics 2025-06-26 Tianchen Qian

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

Mediation analysis in causal inference has traditionally focused on binary exposures and deterministic interventions, and a decomposition of the average treatment effect in terms of direct and indirect effects. In this paper we present an…

Methodology · Statistics 2020-11-17 Iván Díaz , Nima Hejazi

Mediation analysis aims to decipher the underlying causal mechanisms between an exposure, an outcome, and intermediate variables called mediators. Initially developed for fixed-time mediator and outcome, it has been extended to the…

Methodology · Statistics 2025-01-15 K. Le Bourdonnec , L. Valeri , C. Proust-Lima

Causal mediation analysis seeks to investigate how the treatment effect of an exposure on outcomes is mediated through intermediate variables. Although many applications involve longitudinal data, the existing methods are not directly…

Applications · Statistics 2021-02-24 Shuxi Zeng , Stacy Rosenbaum , Elizabeth Archie , Susan Alberts , Fan Li

Causal mediation analysis is widely used to investigate how causal effects operate through specific pathways linking treatments or exposures to outcomes. Recently, \texttt{crumble} was developed to enable nonparametric estimation of several…

Methodology · Statistics 2026-04-14 Richard Liu , Nicholas T. Williams , Kara E. Rudolph , Ivan Diaz

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

A stepped wedge cluster randomized trial is a type of longitudinal cluster design that sequentially switches clusters to intervention over time until all clusters are treated. While the traditional posttest-only parallel design requires…

Applications · Statistics 2021-01-05 Fan Li

Causal mediation analysis examines causal pathways linking exposures to disease. The estimation of interventional effects, which are mediation estimands that overcome certain identifiability problems of natural effects, has been advanced…

The traditional model specification of stepped-wedge cluster-randomized trials assumes a homogeneous treatment effect across time while adjusting for fixed-time effects. However, when treatment effects vary over time, the constant effect…

Mediation analysis seeks to identify and quantify the paths by which an exposure affects an outcome. Intermediate variables which are effected by the exposure and which effect the outcome are known as mediators. There exists extensive work…

Methodology · Statistics 2020-11-13 James P. Long , Ehsan Irajizad , James D. Doecke , Kim-Anh Do , Min Jin Ha

Randomized controlled trials (RCTs) are often underpowered to detect treatment heterogeneity in subgroups defined by cross-classifications of multiple covariates, due to sparse sample sizes in some strata. External RCT data can help, but…

Methodology · Statistics 2026-04-23 Youqi Yang , Walter Dempsey , Bhramar Mukherjee