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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 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

The International Council for Harmonization (ICH) E9 (R1) addendum provides the estimand framework to formulate treatment effects in a clinical trial. One of the attributes of an estimand the framework describes is intercurrent events.…

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

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

The ICH E9(R1) addendum (2019) proposed principal stratification (PS) as one of five strategies for dealing with intercurrent events. Therefore, understanding the strengths, limitations, and assumptions of PS is important for the broad…

Principal stratification (PS) is a commonly used approach for understanding the mechanisms through which a treatment affects an outcome. The goal of this work is to extend the PS framework to studies with continuous treatments, which…

Methodology · Statistics 2025-05-20 Joseph Antonelli , Minxuan Wu , Fabrizia Mealli , Brenden Beck , Alessandra Mattei

In causal inference, principal stratification is a framework for dealing with a posttreatment intermediate variable between a treatment and an outcome, in which the principal strata are defined by the joint potential values of the…

Methodology · Statistics 2021-04-20 Zhichao Jiang , Peng Ding

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

Causal inference is best understood using potential outcomes. This use is particularly important in more complex settings, that is, observational studies or randomized experiments with complications such as noncompliance. The topic of this…

Statistics Theory · Mathematics 2007-06-13 Donald B. Rubin

In clinical trials, principal stratification analysis is commonly employed to address the issue of truncation by death, where a subject dies before the outcome can be measured. However, in practice, many survivor outcomes may remain…

Methodology · Statistics 2025-07-08 Wei Li , Yuan Liu , Shanshan Luo , Zhi Geng

Recurrent events often serve as key endpoints in clinical studies but may be prematurely truncated by terminal events such as death, creating selection bias and complicating causal inference. To address this challenge, we develop a Bayesian…

Methodology · Statistics 2026-03-18 Yuki Ohnishi , Michael O. Harhay , Guangyu Tong , Fan Li

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

In randomized controlled trials (RCTs) that focus on time-to-event outcomes, intercurrent events can arise in two ways: as semi-competing events, which modify the hazard of the primary outcome events, or as competing events, which make the…

Methodology · Statistics 2026-05-26 Yuhao Deng , Shasha Han , Xiao-Hua Zhou

In clinical trials, patients may discontinue treatments prematurely, breaking the initial randomization and, thus, challenging inference. Stakeholders in drug development are generally interested in going beyond the Intention-To-Treat (ITT)…

Principal stratification is a causal framework to analyze randomized experiments with a post-treatment variable between the treatment and endpoint variables. Because the principal strata defined by the potential outcomes of the…

Statistics Theory · Mathematics 2015-07-22 Zhichao Jiang , Peng Ding , Zhi Geng

Post-treatment confounding is a common problem in causal inference, including special cases of noncompliance, truncation by death, surrogate endpoint, etc. Principal stratification (Frangakis and Rubin 2002) is a general framework for…

Computation · Statistics 2023-04-07 Bo Liu , Fan Li

Although randomized controlled trials have long been regarded as the ``gold standard'' for evaluating treatment effects, there is no natural prevention from post-treatment events. For example, non-compliance makes the actual treatment…

Methodology · Statistics 2025-04-25 Qinqing Liu , Xiang Peng , Tao Zhang , Yuhao Deng

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

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
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