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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

New text as data techniques offer a great promise: the ability to inductively discover measures that are useful for testing social science theories of interest from large collections of text. We introduce a conceptual framework for making…

Machine Learning · Statistics 2018-02-08 Naoki Egami , Christian J. Fong , Justin Grimmer , Margaret E. Roberts , Brandon M. Stewart

Inferring causal effects of treatments is a central goal in many disciplines. The potential outcomes framework is a main statistical approach to causal inference, in which a causal effect is defined as a comparison of the potential outcomes…

Methodology · Statistics 2018-01-04 Peng Ding , Fan Li

This paper serves as a literature review of methodology concerning the (modern) causal inference methods to address the causal estimand with observational/survey data that have been or will be used in social science research. Mainly, this…

Econometrics · Economics 2024-08-02 Guanghui Pan

Inferring causal effects from an observational study is challenging because participants are not randomized to treatment. Observational studies in infectious disease research present the additional challenge that one participant's treatment…

Methodology · Statistics 2020-12-25 Brian G. Barkley , Michael G. Hudgens , John D. Clemens , Mohammad Ali , Michael E. Emch

Causal inference analysis is the estimation of the effects of actions on outcomes. In the context of healthcare data this means estimating the outcome of counter-factual treatments (i.e. including treatments that were not observed) on a…

Methodology · Statistics 2018-03-21 Yishai Shimoni , Chen Yanover , Ehud Karavani , Yaara Goldschmnidt

The ICH E9 (R1) addendum on estimands, coupled with recent advancements in causal inference, has prompted a shift towards using model-free treatment effect estimands that are more closely aligned with the underlying scientific question.…

Methodology · Statistics 2024-10-11 Stijn Vansteelandt , Kelly Van Lancker

Matching and weighting methods for observational studies involve the choice of an estimand, the causal effect with reference to a specific target population. Commonly used estimands include the average treatment effect in the treated (ATT),…

Methodology · Statistics 2023-07-12 Noah Greifer , Elizabeth A. Stuart

The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment…

Estimating the causal effect of a treatment or health policy with observational data can be challenging due to an imbalance of and a lack of overlap between treated and control covariate distributions. In the presence of limited overlap,…

Methodology · Statistics 2025-03-24 Martha Barnard , Jared D. Huling , Julian Wolfson

Causal inference is the goal of randomized trials and many observational studies. The first step in a formal causal inference framework is to define the causal estimand, and in both types of study this can be intuitively defined as the…

Methodology · Statistics 2025-09-09 Margarita Moreno-Betancur , Rushani Wijesuriya , John B. Carlin

In longitudinal studies where units are embedded in space or a social network, interference may arise, meaning that a unit's outcome can depend on treatment histories of others. The presence of interference poses significant challenges for…

Methodology · Statistics 2025-08-26 Ye Wang , Michael Jetsupphasuk

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…

The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a…

Other Quantitative Biology · Quantitative Biology 2023-04-17 Steven Sun , Hans-Jochen Weber , Emily Butler , Kaspar Rufibach , Satrajit Roychoudhury

The analysis of randomized controlled trials is often complicated by intercurrent events (IEs) -- events that occur after treatment initiation and affect either the interpretation or existence of outcome measurements. Examples include…

Methodology · Statistics 2026-04-07 Sizhu Lu , Yanyao Yi , Yongming Qu , Huayu Karen Liu , Ting Ye , Peng Ding

This paper discusses the fundamental principles of causal inference - the area of statistics that estimates the effect of specific occurrences, treatments, interventions, and exposures on a given outcome from experimental and observational…

Methodology · Statistics 2021-12-03 Francesca Dominici , Falco J. Bargagli-Stoffi , Fabrizia Mealli

Causal inference methods are gaining increasing prominence in pharmaceutical drug development in light of the recently published addendum on estimands and sensitivity analysis in clinical trials to the E9 guideline of the International…

Methodology · Statistics 2021-04-30 Jack Bowden , Bjoern Bornkamp , Ekkehard Glimm , Frank Bretz

In biomedical research, repeated measurements within each subject are often processed to remove artifacts and unwanted sources of variation. The resulting data are used to construct derived outcomes that act as proxies for scientific…

Methodology · Statistics 2026-02-03 Zihang Wang , Razieh Nabi , Benjamin B. Risk

Under a composite estimand strategy, the occurrence of the intercurrent event is incorporated into the endpoint definition, for instance by assigning a poor outcome value to patients who experience the event. Composite strategies are…

Methodology · Statistics 2025-07-01 Brennan C Kahan , Tra My Pham , Conor Tweed , Tim P Morris

This work develops a flexible inferential framework for nonparametric causal inference in time-to-event settings, based on stochastic interventions defined through multiplicative scaling of the intensity governing an intermediate event…

Methodology · Statistics 2026-02-04 Helene Charlotte Wiese Rytgaard , Mark van der Laan