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Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as clinicians or policymakers, it…

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…

统计方法学 · 统计学 2025-02-06 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

The ICH E9 addendum introduces the term intercurrent event to refer to events that happen after randomisation and that can either preclude observation of the outcome of interest or affect its interpretation. It proposes five strategies for…

统计方法学 · 统计学 2021-07-12 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

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…

Randomized controlled trials (RCT) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the…

应用统计 · 统计学 2020-06-08 Yongming Qu , Linda Shurzinske , Shanthi Sethuraman

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.…

统计方法学 · 统计学 2026-05-28 Xiaoxiao Zhou , Joyce Chen , Pallavi Mishra-Kalyani , Xiaoxue Li , Yuan Li Shen , Shu Wang , Susan Halabi , Fan Li

The estimand framework proposed by ICH in 2017 has brought fundamental changes in the pharmaceutical industry. It clearly describes how a treatment effect in a clinical question should be precisely defined and estimated, through attributes…

其他统计学 · 统计学 2025-12-09 Jinghong Zeng

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)…

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.…

统计方法学 · 统计学 2024-10-11 Stijn Vansteelandt , Kelly Van Lancker

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…

统计方法学 · 统计学 2024-12-31 Matias Janvin , Jessica G. Young , Pål C. Ryalen , Mats J. Stensrud

Researchers are often interested in treatment effects on outcomes that are only defined conditional on a post-treatment event status. For example, in a study of the effect of different cancer treatments on quality of life at end of…

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…

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…

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…

统计方法学 · 统计学 2022-09-29 Alexandra Bühler , Richard J. Cook , Jerald F. Lawless

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…

应用统计 · 统计学 2023-07-24 Jonathan Siegel , Hans-Jochen Weber , Stefan Englert , Feng Liu

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…

应用统计 · 统计学 2020-06-01 Yongming Qu , Junxiang Luo , Stephen J. Ruberg

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…

统计方法学 · 统计学 2026-04-07 Sizhu Lu , Yanyao Yi , Yongming Qu , Huayu Karen Liu , Ting Ye , Peng Ding

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…

统计方法学 · 统计学 2025-07-21 Sunita Rehal , Nicky Best , Sarah Watts , Thomas Drury

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…

统计方法学 · 统计学 2025-10-20 Yixin Fang , Man Jin

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…

统计方法学 · 统计学 2022-04-06 Johann Gaebler , William Cai , Guillaume Basse , Ravi Shroff , Sharad Goel , Jennifer Hill
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