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In interventional health studies, causal mediation analysis can be employed to investigate mechanisms through which the intervention affects the targeted health outcome. Identifying direct and indirect (i.e. mediated) effects from empirical…

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

Understanding how the causal effect of a treatment evolves over time, including the potential for waning, is important for informed decisions on treatment discontinuation or repetition. For example, waning vaccine protection influences…

Methodology · Statistics 2025-11-25 Eni Musta , Joris Mooij

When choosing estimands and estimators in randomized clinical trials, caution is warranted as intercurrent events, such as - due to patients who switch treatment after disease progression, are often extreme. Statistical analyses may then…

Applications · Statistics 2023-03-13 Hege Michiels , An Vandebosch , Stijn Vansteelandt

Randomised controlled trials in reproductive medicine are often subject to outcome truncation, where study outcomes are only defined in a subset of participants. Examples include birthweight (measurable only in the subgroup of participants…

In the absence of data from a randomized trial, researchers often aim to use observational data to draw causal inference about the effect of a treatment on a time-to-event outcome. In this context, interest often focuses on the…

Methodology · Statistics 2021-06-15 Ted Westling , Alex Luedtke , Peter Gilbert , Marco Carone

In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method…

Methodology · Statistics 2019-04-19 Francisco J. Rubio , Bernard Rachet , Roch Giorgi , Camille Maringe , Aurelien Belot

The call for patient-focused drug development is loud and clear, as expressed in the 21st Century Cures Act and in recent guidelines and initiatives of regulatory agencies. Among the factors contributing to modernized drug development and…

Assessing causal effects in the presence of unobserved confounding is a challenging problem. Existing studies leveraged proxy variables or multiple treatments to adjust for the confounding bias. In particular, the latter approach attributes…

Methodology · Statistics 2023-10-17 Yong Wu , Mingzhou Liu , Jing Yan , Yanwei Fu , Shouyan Wang , Yizhou Wang , Xinwei Sun

In a clinical trial with a survival outcome, an interim analysis is often performed to allow for early stopping for efficacy. If the interim analysis is early in the trial, one might conclude that a new treatment is more effective (compared…

Methodology · Statistics 2023-05-09 Marianne A Jonker , Steven Teerenstra

The number of recurrent events before a terminating event is often of interest. For instance, death terminates an individual's process of rehospitalizations and the number of rehospitalizations is an important indicator of economic cost. We…

Methodology · Statistics 2021-12-30 Willem van den Boom , Maria De Iorio , Marta Tallarita

Cardiovascular diseases are major causes of mortality globally. They often co-occur and are interrelated, leading to partial-order relationships among their onset times. However, these onset times are subject to informative censoring due to…

Methodology · Statistics 2026-04-07 Tonghui Yu , Liming Xiang

In studies on lifetimes, occasionally, the population contains statistical units that are born before the data collection has started. Left-truncated are units that deceased before this start. For all other units, the age at the study start…

Methodology · Statistics 2024-06-04 Anne-Marie Toparkus , Rafael Weißbach

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…

Methodology · Statistics 2025-06-24 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

In clinical trials, patients may discontinue treatments prematurely, breaking the initial randomization and, thus, challenging inference. Stakeholders in drug development are generally interested in going beyond the Intention-To-Treat (ITT)…

When making treatment selection decisions, it is essential to include a causal effect estimation analysis to compare potential outcomes under different treatments or controls, assisting in optimal selection. However, merely estimating…

Machine Learning · Statistics 2024-10-08 Sherly Alfonso-Sánchez , Kristina P. Sendova , Cristián Bravo

In survival analysis, estimating the fraction of 'immune' or 'cured' subjects who will never experience the event of interest, requires a sufficiently long follow-up period. A few statistical tests have been proposed to test the assumption…

Methodology · Statistics 2026-01-13 Tsz Pang Yuen , Eni Musta , Ingrid Van Keilegom

Patient reported outcomes including quality of life (QoL) assessments are increasingly being included as either primary or secondary outcomes in randomized controlled trials. While making the outcomes more relevant for patients it entails a…

Methodology · Statistics 2019-10-29 Andreas Kryger Jensen , Theis Lange

Comparing the survival times among two groups is a common problem in time-to-event analysis, for example if one would like to understand whether one medical treatment is superior to another. In the standard survival analysis setting, there…

Methodology · Statistics 2023-07-07 Dennis Dobler , Eni Musta

Researchers are often interested in estimating effects of generalized time-varying treatment strategies on the mean of an outcome at one or more selected follow-up times of interest. For example, the Medications and Weight Gain in PCORnet…