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Subgroup analyses of randomized controlled trials (RCTs) constitute an important component of the drug development process in precision medicine. In particular, subgroup analyses of early-stage trials often influence the design and…

Methodology · Statistics 2025-02-12 Daniel Schwartz , Riddhiman Saha , Steffen Ventz , Lorenzo Trippa

For linear regression models with cross-section or panel data, it is natural to assume that the disturbances are clustered in two dimensions. However, the finite-sample properties of two-way cluster-robust tests and confidence intervals are…

Econometrics · Economics 2026-03-13 James G. MacKinnon , Morten Ørregaard Nielsen , Matthew D. Webb

This paper provides robust estimators and efficient inference of causal effects involving multiple interacting mediators. Most existing works either impose a linear model assumption among the mediators or are restricted to handle…

Methodology · Statistics 2024-01-12 Haoyu Wei , Hengrui Cai , Chengchun Shi , Rui Song

Mediation analysis aims to identify and estimate the effect of an exposure on an outcome that is mediated through one or more intermediate variables. In the presence of multiple intermediate variables, two pertinent methodological questions…

Quantitative Methods · Quantitative Biology 2026-01-06 Allan Jérolon , Flora Alarcon , Florence Pittion , Magali Richard , Olivier François , Etienne E. Birmelé , Vittorio Perduca

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…

The parallel cluster randomized trial with baseline (PB-CRT) is a common variant of the standard parallel cluster randomized trial (P-CRT). We define two natural estimands in the context of PB-CRTs with informative cluster sizes, the…

Methodology · Statistics 2025-05-01 Kenneth Menglin Lee , Fan Li

It is often of interest to decompose a total effect of an exposure into the component that acts on the outcome through some mediator and the component that acts independently through other pathways. Said another way, we are interested in…

Statistics Theory · Mathematics 2016-01-21 Peng Ding , Tyler J. VanderWeele

Mediation analysis is a useful tool to evaluate surrogate endpoints in clinical trials. We propose a novel method, the M-survival learner, for estimating heterogeneous indirect treatment effects in the presence of censored outcomes. The…

Methodology · Statistics 2026-04-16 Xingyu Li , Qing Liu , Xun Jiang , Hong Amy Xia , Brian P. Hobbs , Peng Wei

Unscheduled treatment interruptions may lead to reduced quality of care in radiation therapy (RT). Identifying the RT prescription dose effects on the outcome of treatment interruptions, mediated through doses distributed into different…

Methodology · Statistics 2024-09-25 Zijin Liu , Zhihui Liu , Ali Hosni , John Kim , Bei Jiang , Olli Saarela

Causal mediation analyses investigate the mechanisms through which causes exert their effects, and are therefore central to scientific progress. The literature on the non-parametric definition and identification of mediational effects in…

Machine Learning · Statistics 2025-06-13 Richard Liu , Nicholas T. Williams , Kara E. Rudolph , Iván Díaz

Cluster randomized trials (CRTs) frequently recruit a small number of clusters, therefore necessitating the application of small-sample corrections for valid inference. A recent systematic review indicated that CRTs reporting…

Methodology · Statistics 2022-09-07 Xueqi Wang , Elizabeth L. Turner , Fan Li

Causal mediation analysis is used to evaluate direct and indirect causal effects of a treatment on an outcome of interest through an intermediate variable or a mediator.It is difficult to identify the direct and indirect causal effects…

Applications · Statistics 2020-01-14 Wei Li , Chunchen Liu , Zhi Geng , John Murray

We address estimation of intervention effects in experimental designs in which (a) interventions are assigned at the cluster level; (b) clusters are selected to form pairs, matched on observed characteristics; and (c) intervention is…

Methodology · Statistics 2014-11-24 Zhenke Wu , Constantine E. Frangakis , Thomas A. Louis , Daniel O. Scharfstein

Mediation analysis is critical to understanding the mechanisms underlying exposure-outcome relationships. In this paper, we identify the instrumental variable (IV)-direct effect of the exposure on the outcome not through the mediator, using…

Methodology · Statistics 2020-06-16 Kara E Rudolph , Oleg Sofrygin , Mark J van der Laan

This paper combines causal mediation analysis with double machine learning to control for observed confounders in a data-driven way under a selection-on-observables assumption in a high-dimensional setting. We consider the average indirect…

Econometrics · Economics 2021-02-17 Helmut Farbmacher , Martin Huber , Lukáš Lafférs , Henrika Langen , Martin Spindler

Mediation analysis seeks to infer how much of the effect of an exposure on an outcome can be attributed to specific pathways via intermediate variables or mediators. This requires identification of so-called path-specific effects. These…

Methodology · Statistics 2019-06-06 Johan Steen , Stijn Vansteelandt

Cluster-randomized trials (CRTs) are a well-established class of designs for evaluating community-based interventions. An essential task in planning these trials is determining the number of clusters and cluster sizes needed to achieve…

This article investigates the model-robustness of fixed-effects models for analyzing a broad class of longitudinal cluster trials (CTs) such as stepped-wedge, parallel-with-baseline and crossover designs, encompassing both randomized (CRTs)…

Methodology · Statistics 2026-04-10 Kenneth M. Lee , Fan Li

Methods for estimating heterogeneous treatment effects (HTE) from observational data have largely focused on continuous or binary outcomes, with less attention paid to survival outcomes and almost none to settings with competing risks. In…

Methodology · Statistics 2024-09-30 Shenbo Xu , Raluca Cobzaru , Stan N. Finkelstein , Roy E. Welsch , Kenney Ng , Zach Shahn

Pragmatic trials evaluating health care interventions often adopt cluster randomization due to scientific or logistical considerations. Previous reviews have shown that co-primary endpoints are common in pragmatic trials but infrequently…

Methodology · Statistics 2022-05-03 Siyun Yang , Mirjam Moerbeek , Monica Taljaard , Fan Li