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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

Causal effect estimation from observational data is one of the essential problems in causal inference. However, most estimation methods rely on the strong assumption that all confounders are observed, which is impractical and untestable in…

Methodology · Statistics 2023-02-14 Yubai Yuan , Annie Qu

Causal inference is a central goal across many scientific disciplines. Over the past several decades, three major frameworks have emerged to formalize causal questions and guide their analysis: the potential outcomes framework, structural…

Statistics Theory · Mathematics 2026-02-12 Linbo Wang , Thomas Richardson , James Robins

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

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…

The estimand framework proposes different strategies to address intercurrent events. The treatment policy strategy seems to be the most favoured as it is closely aligned with the pre-addendum intention-to-treat principle. All data for all…

Methodology · Statistics 2025-07-21 Sunita Rehal , Nicky Best , Sarah Watts , Thomas Drury

Since the release of the ICH E9(R1) addendum on estimands, its application in non-inferiority trials has received far less attention than in superiority settings. A key conclusion from Lynggaard et al. was that the "choice of…

Applications · Statistics 2026-03-12 Tobias Mütze , Helle Lynggaard , Sunita Rehal , Oliver N. Keene , Marian Mitroiu , David Wright

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

Average and conditional treatment effects are fundamental causal quantities used to evaluate the effectiveness of treatments in various critical applications, including clinical settings and policy-making. Beyond the gold-standard…

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

A Real-World Evidence (RWE) Scientific Working Group (SWG) of the American Statistical Association Biopharmaceutical Section (ASA BIOP) has been reviewing statistical considerations for the generation of RWE to support regulatory…

Applications · Statistics 2023-07-04 Jie Chen , Daniel Scharfstein , Hongwei Wang , Binbing Yu , Yang Song , Weili He , John Scott , Xiwu Lin , Hana Lee

While rankings are at the heart of social science research, little is known about how to analyze ranking data in experimental studies. This paper introduces a potential-outcomes framework to perform causal inference when outcome data are…

Methodology · Statistics 2023-01-12 Yuki Atsusaka

The interpretability of prediction mechanisms with respect to the underlying prediction problem is often unclear. While several studies have focused on developing prediction models with meaningful parameters, the causal relationships…

Machine Learning · Statistics 2017-09-05 Patrick Blöbaum , Shohei Shimizu

COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We…

In studies of discrimination, researchers often seek to estimate a causal effect of race or gender on outcomes. For example, in the criminal justice context, one might ask whether arrested individuals would have been subsequently charged or…

Methodology · Statistics 2022-04-06 Johann Gaebler , William Cai , Guillaume Basse , Ravi Shroff , Sharad Goel , Jennifer Hill

Case-control designs are an important tool in contrasting the effects of well-defined treatments. In this paper, we reconsider classical concepts, assumptions and principles and explore when the results of case-control studies can be…

Methodology · Statistics 2021-05-06 Bas B. L. Penning de Vries , Rolf H. H. Groenwold

This paper introduces a simple framework of counterfactual estimation for causal inference with time-series cross-sectional data, in which we estimate the average treatment effect on the treated by directly imputing counterfactual outcomes…

Methodology · Statistics 2022-08-16 Licheng Liu , Ye Wang , Yiqing Xu

We describe a design-based framework for drawing causal inference in general randomized experiments. Causal effects are defined as linear functionals evaluated at unit-level potential outcome functions. Assumptions about the potential…

Methodology · Statistics 2025-08-15 Christopher Harshaw , Fredrik Sävje , Yitan Wang

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…

The fundamental challenge of drawing causal inference is that counterfactual outcomes are not fully observed for any unit. Furthermore, in observational studies, treatment assignment is likely to be confounded. Many statistical methods have…

Methodology · Statistics 2022-08-01 Harsh Parikh , Carlos Varjao , Louise Xu , Eric Tchetgen Tchetgen