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Related papers: Estimands in Real-World Evidence Studies

200 papers

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 current COVID-19 pandemic poses numerous challenges for ongoing clinical trials and provides a stress-testing environment for the existing principles and practice of estimands in clinical trials. The pandemic may increase the rate of…

Methodology · Statistics 2023-02-02 Yongming Qu , Ilya Lipkovich

Objective: Traditionally validation of surrogate endpoints has been carried out using RCT data. However, RCT data may be too limited to validate surrogate endpoints. In this paper, we sought to improve validation of surrogate endpoints with…

Applications · Statistics 2021-12-17 Lorna Wheaton , Anastasios Papanikos , Anne Thomas , Sylwia Bujkiewicz

The 21st Century Cures Act of 2016 includes a provision for the U.S. Food and Drug Administration (FDA) to evaluate the potential use of real-world evidence (RWE) to support new indications for use for previously approved drugs, and to…

Applications · Statistics 2022-06-15 Susan Gruber , Rachael V. Phillips , Hana Lee , Martin Ho , John Concato , Mark J. van der Laan

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…

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.…

Real-World Data (RWD), with its large sample sizes and rich clinical detail, offers a compelling alternative to randomized controlled trials (RCTs) for studying treatment effects in diverse and complex patient populations. However, its…

Applications · Statistics 2026-05-26 Yifei Xu , Hwiyoung Lee , Zhenyao Ye , Yezhi Pan , Jingsong Zhou , Yun Yang , Chixiang Chen , Shuo Chen

A platform trial is an innovative clinical trial design that uses a master protocol to evaluate multiple treatments, where patients are often assigned to different subsets of treatment arms based on individual characteristics, enrollment…

Applied researchers in biomedicine and related fields are often interested in estimating the causal effect of a treatment or intervention. Although randomized clinical trials are considered the gold standard for establishing causal effects,…

The integration of real-world data (RWD) and randomized controlled trials (RCT) is increasingly important for advancing causal inference in scientific research. This combination holds great promise for enhancing the efficiency of causal…

Methodology · Statistics 2024-07-02 Xi Lin , Jens Magelund Tarp , Robin J. Evans

To precisely define the treatment effect of interest in a clinical trial, the ICH E9 estimand addendum describes that relevant so-called intercurrent events should be identified and strategies specified to deal with them. Handling…

Methodology · Statistics 2025-02-06 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

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

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…

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

The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…

Applications · Statistics 2023-09-25 Camila Olarte Parra , Rhian M. Daniel , David Wright , Jonathan W. Bartlett

In contrast to problems of interference in (exogenous) treatments, models of interference in unit-specific (endogenous) outcomes do not usually produce a reduced-form representation where outcomes depend on other units' treatment status…

Econometrics · Economics 2025-06-17 Konrad Menzel

Electronic Health Records (EHRs) have been increasingly used as real-world evidence (RWE) to support the discovery and validation of new drug indications. This paper surveys current approaches to EHR-based drug repurposing, covering data…

Applications · Statistics 2025-11-21 Nabasmita Talukdar , Xiaodan Zhang , Shreya Paithankar , Hui Wang , Bin Chen

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

Stepped-wedge cluster-randomized trials (SW-CRTs) are widely used in healthcare and implementation science, providing an ethical advantage by ensuring all clusters eventually receive the intervention. The staggered rollout of treatment…

Methodology · Statistics 2026-04-03 Xi Fang , Xueqi Wang , Patrick J. Heagerty , Bingkai Wang , Fan Li