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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

Assessing the causal effect of time-varying exposures on recurrent event processes is challenging in the presence of a terminating event. Our objective is to estimate both the short-term and delayed marginal causal effects of exposures on…

In multisite trials, researchers are often interested in several inferential goals: estimating treatment effects for each site, ranking these effects, and studying their distribution. This study seeks to identify optimal methods for…

Methodology · Statistics 2024-04-03 JoonHo Lee , Jonathan Che , Sophia Rabe-Hesketh , Avi Feller , Luke Miratrix

In competing event settings, a counterfactual contrast of cause-specific cumulative incidences quantifies the total causal effect of a treatment on the event of interest. However, effects of treatment on the competing event may indirectly…

Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Researchers must understand the effects of various treatments on recurrent events and investigate the underlying mediation mechanisms by which…

Methodology · Statistics 2025-07-08 Yan-Lin Chen , Yan-Hong Chen , Pei-Fang Su , Huang-Tz Ou , An-Shun Tai

Decomposing an exposure effect on an outcome into separate natural indirect effects through multiple mediators requires strict assumptions, such as correctly postulating the causal structure of the mediators, and no unmeasured confounding…

Methodology · Statistics 2021-02-04 Wen Wei Loh , Beatrijs Moerkerke , Tom Loeys , Stijn Vansteelandt

Environmental health studies are increasingly measuring endogenous omics data ($\boldsymbol{M}$) to study intermediary biological pathways by which an exogenous exposure ($\boldsymbol{A}$) affects a health outcome ($\boldsymbol{Y}$), given…

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

Often in follow-up studies intermediate events occur in some patients, such as reinterventions or adverse events. These intermediate events directly affect the shapes of their longitudinal profiles. Our work is motivated by two studies in…

This research was motivated by studying anti-drug antibody (ADA) formation and its potential impact on long-term benefit of a biologic treatment in a randomized controlled trial, in which ADA status was not only unobserved in the control…

Methodology · Statistics 2021-01-13 Shengchun Kong , Dominik Heinzmann , Sabine Lauer , Tian Lu

A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding…

Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. A naive conditioning on intercurrent events does not have…

Methodology · Statistics 2021-11-17 Mats J. Stensrud , Oliver Dukes

There is a growing literature on finding so-called optimal treatment rules, which are rules by which to assign treatment to individuals based on an individual's characteristics, such that a desired outcome is maximized. A related goal…

Applications · Statistics 2021-01-22 Kara E. Rudolph , Ivan Diaz

The goal of mediation analysis is to study the effect of exposure on an outcome interceded by a mediator. Two simple hypotheses are tested: the effect of the exposure on the mediator, and the effect of the mediator on the outcome. When…

Statistics Theory · Mathematics 2021-06-01 Yotam Leibovici , Yair Goldberg

The ICH E9 addendum introduces the term intercurrent event to refer to events that happen after randomisation and that can either preclude observation of the outcome of interest or affect its interpretation. It proposes five strategies for…

Methodology · Statistics 2021-07-12 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

Mediation analysis is a strategy for understanding the mechanisms by which treatments or interventions affect later outcomes. Mediation analysis is frequently applied in randomized trial settings, but typically assumes: a) that randomized…

Methodology · Statistics 2021-12-30 Kara E. Rudolph , Nicholas Williams , Ivan Diaz

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…

Methodology · Statistics 2025-06-24 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

Understanding the pathways whereby an intervention has an effect on an outcome is a common scientific goal. A rich body of literature provides various decompositions of the total intervention effect into pathway specific effects.…

Methodology · Statistics 2020-01-20 David Benkeser

Predicting the timing and occurrence of events is a major focus of data science applications, especially in the context of biomedical research. Performance for models estimating these outcomes, often referred to as time-to-event or survival…

Methodology · Statistics 2024-06-07 Ying Jin , Andrew Leroux

Analyses of causal mediation often involve exposure-induced confounders or, relatedly, multiple mediators. In such applications, researchers aim to estimate a variety of different quantities, including interventional direct and indirect…

Methodology · Statistics 2025-06-18 Jesse Zhou , Geoffrey T. Wodtke