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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…

Methodology · Statistics 2021-07-12 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

Data collected in clinical trials are often composed of multiple types of variables. For example, laboratory measurements and vital signs are longitudinal data of continuous or categorical variables, adverse events may be recurrent events,…

Methodology · Statistics 2023-01-12 Tuo Wang , Rachel Zilinskas , Ying Li , Yongming Qu

Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown…

Methodology · Statistics 2016-08-12 Layla Parast , Tianxi Cai , Lu Tian

Omitted variable bias can affect treatment effect estimates obtained from observational data due to the lack of random assignment to treatment groups. Sensitivity analyses adjust these estimates to quantify the impact of potential omitted…

Methodology · Statistics 2010-11-10 Carrie A. Hosman , Ben B. Hansen , Paul W. Holland

In this paper we consider a time-to-event variable $T$ that is subject to random right censoring, and we assume that the censoring time $C$ is stochastically dependent on $T$ and that there is a positive probability of not observing the…

Methodology · Statistics 2024-03-14 Morine Delhelle , Ingrid Van Keilegom

Noncompliance and missing data often occur in randomized trials, which complicate the inference of causal effects. When both noncompliance and missing data are present, previous papers proposed moment and maximum likelihood estimators for…

Methodology · Statistics 2014-09-04 Hua Chen , Peng Ding , Zhi Geng , Xiao-Hua Zhou

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

Tipping points characterize situations where a regulated system may experience a sudden and irreversible change and are generally associated with a random state of the system below which the change materializes. In this paper, we study a…

Optimization and Control · Mathematics 2026-02-25 Jean-Paul Décamps , Fabien Gensbittel , Thomas Mariotti , Stéphane Villeneuve

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 analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. As the censoring mechanism is usually unknown, analyses typically employ the assumption of non-informative censoring. While…

Methodology · Statistics 2020-07-17 Kelly Van Lancker , Oliver Dukes , Stijn Vansteelandt

Difference-in-differences (DiD) is one of the most popular approaches for empirical research in economics, political science, and beyond. Identification in these models is based on the conditional parallel trends assumption: In the absence…

Econometrics · Economics 2025-10-13 Philipp Bach , Sven Klaassen , Jannis Kueck , Mara Mattes , Martin Spindler

This paper presents a framework for causal inference in the presence of censored data,where the failure time is marked by a continuous variable referred to as a mark.The mark is observed after treatment and is not meaningful when the…

Methodology · Statistics 2026-04-20 Lianqiang Qu , Long Lv , Liuquan Sun

Evaluating the performance of a prediction model is a common task in medical statistics. Standard accuracy metrics require the observation of the true outcomes. This is typically not possible in the setting with time-to-event outcomes due…

Methodology · Statistics 2025-07-18 Zhenwei Yang , Dimitris Rizopoulos , Lisa F. Newcomb , Nicole S. Erler

Missing observations are common in cluster randomised trials. Approaches taken to handling such missing data include: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed…

Methodology · Statistics 2014-07-18 Karla Diaz-Ordaz , Michael G. Kenward , Manuel Gomes , Richard Grieve

We consider studies where multiple measures on an outcome variable are collected over time, but some subjects drop out before the end of follow up. Analyses of such data often proceed under either a 'last observation carried forward' or…

Methodology · Statistics 2022-07-26 Oliver Dukes , David Richardson , Eric Tchetgen Tchetgen

Left censoring can occur with relative frequency when analysing recurrent events in epidemiological studies, especially observational ones. Concretely, the inclusion of individuals that were already at risk before the effective initiation…

Methodology · Statistics 2021-02-24 Gilma Hernández-Herrera , David Moriña , Albert Navarro

In comparative effectiveness research, treated and control patients might have a different start of follow-up as treatment is often started later in the disease trajectory. This typically occurs when data from treated and controls are not…

Methodology · Statistics 2024-06-10 Rik van Eekelen , Patrick M. M. Bossuyt , Nan van Geloven

Accurate time-to-event prediction is integral to decision-making, informing medical guidelines, hiring decisions, and resource allocation. Survival analysis, the quantitative framework used to model time-to-event data, accounts for patients…

Machine Learning · Computer Science 2025-08-08 Vincent Jeanselme , Brian Tom , Jessica Barrett

Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary…

Methodology · Statistics 2021-08-20 J Hoogland , J IntHout , M Belias , MM Rovers , RD Riley , FE Harrell , KGM Moons , TPA Debray , JB Reitsma

Blinded sample size re-estimation and information monitoring based on blinded data has been suggested to mitigate risks due to planning uncertainties regarding nuisance parameters. Motivated by a randomized controlled trial in pediatric…

Applications · Statistics 2019-03-07 Tobias Mütze , Susanna Salem , Norbert Benda , Heinz Schmidli , Tim Friede