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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

Summary points: - This article considers the combination of two binary or two time-to-event endpoints to form the primary composite endpoint for leading a trial. - It discusses the relative efficiency of choosing a composite endpoint over…

Applications · Statistics 2020-01-13 Marta Bofill Roig , Jordi Cortés Martínez , Guadalupe Gómez Melis

The estimand framework provides guidance on handling intercurrent events, such as treatment discontinuation, in the analysis of clinical trial responses. Under ICH E9(R1), the treatment policy (TP) strategy incorporates post-discontinuation…

Methodology · Statistics 2026-04-07 Myeongjong Kang , Sangyoon Yi

Intercurrent events (ICEs) and missing values are inevitable in clinical trials of any size and duration, making it difficult to assess the treatment effect for all patients in randomized clinical trials. Defining the appropriate estimand…

Applications · Statistics 2020-06-01 Yongming Qu , Junxiang Luo , Stephen J. Ruberg

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) Addendum provides a framework for defining estimands in clinical trials. Treatment policy strategy is the mostly used…

Applications · Statistics 2024-10-10 Rong Liu , Yongming Qu

The ICH E9(R1) guideline presents a framework of estimand for clinical trials, proposes five strategies for handling intercurrent events (ICEs), and provides a comprehensive discussion and many real-life clinical examples for quantitative…

Methodology · Statistics 2025-10-20 Yixin Fang , Man Jin

The estimand framework is increasingly established to pose research questions in confirmatory clinical trials. In evidence synthesis, the uptake of estimands has been modest, and the PICO (Population, Intervention, Comparator, Outcome)…

Post-randomization events, also known as intercurrent events, such as treatment noncompliance and censoring due to a terminal event, are common in clinical trials. Principal stratification is a framework for causal inference in the presence…

Methodology · Statistics 2023-01-19 Bo Liu , Lisa Wruck , Fan Li

Time-to-event estimands are central to many oncology clinical trials. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest…

Applications · Statistics 2023-07-24 Jonathan Siegel , Hans-Jochen Weber , Stefan Englert , Feng Liu

Intercurrent events, such as treatment switching, rescue medication, dropout, or truncation by death, frequently complicate intention-to-treat analyses in randomized clinical trials. Existing causal inference frameworks typically target…

Methodology · Statistics 2026-03-12 Georgi Baklicharov , Kelly Van Lancker , Stijn Vansteelandt

Performing causal inference in observational studies requires we assume confounding variables are correctly adjusted for. G-computation methods are often used in these scenarios, with several recent proposals using Bayesian versions of…

Methodology · Statistics 2021-10-25 Daniel Daly-Grafstein , Paul Gustafson

We present new results on average causal effects in settings with unmeasured exposure-outcome confounding. Our results are motivated by a class of estimands, e.g., frequently of interest in medicine and public health, that are currently not…

Methodology · Statistics 2023-12-25 Lan Wen , Aaron L. Sarvet , Mats J. Stensrud

We study causal inference in randomized experiments (or quasi-experiments) following a $2\times 2$ factorial design. There are two treatments, denoted $A$ and $B$, and units are randomly assigned to one of four categories: treatment $A$…

Econometrics · Economics 2024-12-12 Mate Kormos , Robert P. Lieli , Martin Huber

Semi-competing risks refer to the phenomenon that the terminal event (such as death) can censor the non-terminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either…

Methodology · Statistics 2024-10-10 Yuhao Deng , Yi Wang , Xiao-Hua Zhou

Observational studies of recurrent event rates are common in biomedical statistics. Broadly, the goal is to estimate differences in event rates under two treatments within a defined target population over a specified followup window.…

Methodology · Statistics 2024-11-13 Arman Oganisian , Anthony Girard , Jon A. Steingrimsson , Patience Moyo

In this paper, we discuss causal inference on the efficacy of a treatment or medication on a time-to-event outcome with competing risks. Although the treatment group can be randomized, there can be confoundings between the compliance and…

Methodology · Statistics 2016-12-06 Cheng Zheng , Ran Dai , Parameswaran Hari , Mei-Jie Zhang

Prediction models are used amongst others to inform medical decisions on interventions. Typically, individuals with high risks of adverse outcomes are advised to undergo an intervention while those at low risk are advised to refrain from…

There is tremendous interest in precision medicine as a means to improve patient outcomes by tailoring treatment to individual characteristics. An individualized treatment rule formalizes precision medicine as a map from patient information…

Machine Learning · Statistics 2020-05-28 Daniel J. Luckett , Eric B. Laber , Michael R. Kosorok

Externally controlled trials are crucial in clinical development when randomized controlled trials are unethical or impractical. These trials consist of a full treatment arm with the experimental treatment and a full external control arm.…

Methodology · Statistics 2025-03-11 Chenyin Gao , Xiang Zhang , Shu Yang

Interference occurs when a unit's treatment (or exposure) affects another unit's outcome. In some settings, units may be grouped into clusters such that it is reasonable to assume that interference, if present, only occurs between…

Methodology · Statistics 2023-08-24 Chanhwa Lee , Donglin Zeng , Michael G. Hudgens