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Principal stratification is a popular framework for causal inference in the presence of an intermediate outcome. While the principal average treatment effects are the standard target of inference, they may be insufficient when interest lies…

Methodology · Statistics 2025-12-29 Xinyuan Chen , Fan Li

Estimands using the treatment policy strategy for addressing intercurrent events are common in Phase III clinical trials. One estimation approach for this strategy is retrieved dropout whereby observed data following an intercurrent event…

The principal stratification has become a popular tool to address a broad class of causal inference questions, particularly in dealing with non-compliance and truncation-by-death problems. The causal effects within principal strata which…

Methodology · Statistics 2022-06-20 Shanshan Luo , Wei Li , Wang Miao , Yangbo He

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In…

Methodology · Statistics 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

Researchers are often interested in treatment effects on outcomes that are only defined conditional on a post-treatment event status. For example, in a study of the effect of different cancer treatments on quality of life at end of…

The target trial framework enables causal inference from longitudinal observational data by emulating randomized trials initiated at multiple time points. Precision is often improved by pooling information across trials, with standard…

Methodology · Statistics 2026-01-08 Edoardo Efrem Gervasoni , Liesbet De Bus , Stijn Vansteelandt , Oliver Dukes

Intercurrent events, common in clinical trials and observational studies, affect the existence or interpretation of final outcomes. Principal stratification addresses this challenge by defining local average treatment effect estimands…

Methodology · Statistics 2025-09-22 Jiaqi Tong , Brennan Kahan , Michael O. Harhay , Fan Li

Practitioners are interested in not only the average causal effect of the treatment on the outcome but also the underlying causal mechanism in the presence of an intermediate variable between the treatment and outcome. However, in many…

Methodology · Statistics 2016-02-04 Peng Ding , Jiannan Lu

Intensity-based multistate models provide a useful framework for characterizing disease processes, the introduction of interventions, loss to follow-up, and other complications arising in the conduct of randomized trials studying complex…

Methodology · Statistics 2022-09-29 Alexandra Bühler , Richard J. Cook , Jerald F. Lawless

We study estimation and inference for heterogeneous principal causal effects with binary treatments and binary intermediate variables. Principal causal effects are subgroup effects within strata defined by potential values of an…

Methodology · Statistics 2026-03-11 Rui Zhang , Charles R. Doss , Jared D. Huling

While recurrent event analyses have been extensively studied, limited attention has been given to causal inference within the framework of recurrent event analysis. We develop a multiply robust estimation framework for causal inference in…

Methodology · Statistics 2025-09-30 Benjamin R. Baer , Trang Bui , Daniel Mork , Robert L. Strawderman , Ashkan Ertefaie

We consider assessing causal mediation in the presence of a post-treatment event (examples include noncompliance, a clinical event, or death). We identify natural mediation effects for the entire study population and for each principal…

Methodology · Statistics 2024-09-13 Chao Cheng , Fan Li

It has recently become popular to define treatment effects for subsets of the target population characterized by variables not observable at the time a treatment decision is made. Characterizing and estimating such treatment effects is…

Statistics Theory · Mathematics 2007-08-30 Marshall M. Joffe , Dylan Small , Chi-Yuan Hsu

In failure-time settings, a competing risk event is any event that makes it impossible for the event of interest to occur. For example, cardiovascular disease death is a competing event for prostate cancer death because an individual cannot…

In semicompeting risks problems, nonterminal time-to-event outcomes such as time to hospital readmission are subject to truncation by death. These settings are often modeled with illness-death models for the hazards of the terminal and…

Methodology · Statistics 2019-02-27 Leah Comment , Fabrizia Mealli , Sebastien Haneuse , Corwin Zigler

Interference occurs when the potential outcomes of a unit depend on the treatment of others. Interference can be highly heterogeneous, where treating certain individuals might have a larger effect on the population's overall outcome. A…

Methodology · Statistics 2025-04-11 Samantha G Dean , Georgia Papadogeorgou , Laura Forastiere

Principal stratification is a framework for making sense of causal effects conditioned on variables that may themselves have been affected by the treatment. For instance, in an evaluation of an educational intervention, some subjects in the…

Methodology · Statistics 2026-05-05 Adam C. Sales , Kirk P. Vanacore , Erin R. Ottmar

Post-treatment variables often complicate causal inference. They appear in many scientific problems, including noncompliance, truncation by death, mediation, and surrogate endpoint evaluation. Principal stratification is a strategy to…

Methodology · Statistics 2024-04-04 Sizhu Lu , Zhichao Jiang , Peng Ding

Researchers addressing post-treatment complications in randomized trials often turn to principal stratification to define relevant assumptions and quantities of interest. One approach for estimating causal effects in this framework is to…

Methodology · Statistics 2016-06-09 Avi Feller , Fabrizia Mealli , Luke Miratrix

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