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Familiar statistical tests and estimates are obtained by the direct observation of cases of interest: a clinical trial of a new drug, for instance, will compare the drug's effects on a relevant set of patients and controls. Sometimes,…

Methodology · Statistics 2010-12-09 Bradley Efron

In the context of having an instrumental variable, the standard practice in causal inference begins by targeting an effect of interest and proceeds by formulating assumptions enabling its identification. We turn this around by adhering to…

Statistics Theory · Mathematics 2026-05-25 Carlos García Meixide , Mark J. van der Laan

Causal mediation analysis is complicated with multiple effect definitions that require different sets of assumptions for identification. This paper provides a systematic explanation of such assumptions. We define five potential outcome…

Methodology · Statistics 2022-09-26 Trang Quynh Nguyen , Ian Schmid , Elizabeth L. Ogburn , Elizabeth A. Stuart

Conventional causal estimands, such as the average treatment effect (ATE), capture how the mean outcome in a population or subpopulation would change if all units were assigned to treatment versus control. Real-world policy changes,…

Methodology · Statistics 2025-12-12 Xiang Zhou , Aleksei Opacic

In time-to-event settings, the presence of competing events complicates the definition of causal effects. Here we propose the new separable effects to study the causal effect of a treatment on an event of interest. The separable direct…

Pragmatic trials increasingly define outcomes using real-world data such as electronic health records, where assessments are collected during routine care rather than at fixed timepoints. Consequently, these uncontrolled assessments may be…

Population-adjusted indirect comparisons (PAICs) are widely used to synthesize evidence when randomized controlled trials enroll different patient populations and head-to-head comparisons are unavailable. Although PAICs adjust for observed…

Methodology · Statistics 2026-02-20 Conor Chandler , Jack Ishak

Meta-analysis, by synthesizing effect estimates from multiple studies conducted in diverse settings, stands at the top of the evidence hierarchy in clinical research. Yet, conventional approaches based on fixed- or random-effects models…

Matching-adjusted indirect comparison (MAIC) has been increasingly employed in health technology assessments (HTA). By reweighting subjects from a trial with individual participant data (IPD) to match the covariate summary statistics of…

Machine Learning · Statistics 2026-05-13 Yixin Fang , Weili He

We consider the problem of indirect comparison, where a treatment arm of interest is absent by design in one randomized controlled trial but available in the other. The former is the target trial, and the latter is the source trial. The…

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

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

The increase in the use of mobile and wearable devices now allows dense assessment of mediating processes over time. For example, a pharmacological intervention may have an effect on smoking cessation via reductions in momentary withdrawal…

Causal mediation analysis is a useful tool for epidemiological research, but it has been criticized for relying on a "cross-world" independence assumption that is empirically difficult to verify and problematic to justify based on…

Methodology · Statistics 2021-09-02 Ryan M. Andrews , Vanessa Didelez

Mediation analysis has been used in many disciplines to explain the mechanism or process that underlies an observed relationship between an exposure variable and an outcome variable via the inclusion of mediators. Decompositions of the…

Methodology · Statistics 2020-08-03 Xin Gao , Li Li , Li Luo

Many research questions concern treatment effects on outcomes that can recur several times in the same individual. For example, medical researchers are interested in treatment effects on hospitalizations in heart failure patients and sports…

Methodology · Statistics 2024-12-31 Matias Janvin , Jessica G. Young , Pål C. Ryalen , Mats J. Stensrud

Standard methods for inference about direct and indirect effects require stringent no unmeasured confounding assumptions which often fail to hold in practice, particularly in observational studies. The goal of this paper is to introduce a…

Methodology · Statistics 2019-09-25 Isabel R. Fulcher , Ilya Shpitser , Stella Marealle , Eric J. Tchetgen Tchetgen

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…

The analysis of large experimental datasets frequently reveals significant interactions that are difficult to interpret within the theoretical framework guiding the research. Some of these interactions actually arise from the presence of…

Applications · Statistics 2017-09-19 Hannes Matuschek , Reinhold Kliegl

Mediation analysis serves as a crucial tool to obtain causal inference based on directed acyclic graphs, which has been widely employed in the areas of biomedical science, social science, epidemiology and psychology. Decomposition of total…

Methodology · Statistics 2020-04-14 Xin Gao , Li Li , Li Luo

Causal inference methods are widely applied in various decision-making domains such as precision medicine, optimal policy and economics. Central to causal inference is the treatment effect estimation of intervention strategies, such as…

Artificial Intelligence · Computer Science 2021-05-31 Tri Dung Duong , Qian Li , Guandong Xu