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The hazard ratio is routinely used as a summary measure to assess the treatment effect in clinical trials with time-to-event endpoints. It is frequently assumed as constant over time although this assumption often does not hold. When the…

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

Stepped-wedge cluster randomised trials (SW-CRTs) increasingly evaluate complex interventions, yet methodological guidance for analysing composite endpoints using generalized pairwise comparisons (GPC)remains limited. This work investigates…

Sample size calculations can be challenging with skewed continuous outcomes in randomized controlled trials (RCTs). Standard t-test-based calculations may require data transformation, which may be difficult before data collection.…

In large observational studies, the case-cohort design is commonly used to reduce the cost associated with covariate measurement. For survival outcomes, literature has suggested that the restricted mean survival time (RMST) be a more…

Methodology · Statistics 2026-05-08 Andy Ni , Wei-En Lu , Bo Lu

Modern randomization methods in clinical trials are invariably adaptive, meaning that the assignment of the next subject to a treatment group uses the accumulated information in the trial. Some of the recent adaptive randomization methods…

Methodology · Statistics 2024-02-12 Alan R. Vazquez , Weng Kee Wong

In observational studies, accurately characterizing variance is critical for sample size determination, yet unaccounted-for variability from propensity score estimation and the resulting weights limit the accuracy of standard variance…

Methodology · Statistics 2026-04-24 Taekwon Hong , Daeyoung Lim , Woojung Bae , Yong Ma

Cumulative probability models (CPMs) are a robust alternative to linear models for continuous outcomes. However, they are not feasible for very large datasets due to elevated running time and memory usage, which depend on the sample size,…

Computation · Statistics 2022-07-15 Chun Li , Guo Chen , Bryan E. Shepherd

The amount of data collected from patients involved in clinical trials is continuously growing. All patient characteristics are potential covariates that could be used to improve clinical trial analysis and power. However, the restricted…

Methodology · Statistics 2021-03-29 Samuel Branders , Alvaro Pereira , Guillaume Bernard , Marie Ernst , Adelin Albert

Composite endpoints that combine multiple outcomes on different scales are common in clinical trials, particularly in chronic conditions. In many of these cases, patients will have to cross a predefined responder threshold in each of the…

Methodology · Statistics 2019-02-20 Martina McMenamin , Jessica K. Barrett , Anna Berglind , James M. S. Wason

The win ratio (WR) statistic is increasingly used to evaluate treatment effects based on prioritized composite endpoints, yet existing Bayesian adaptive designs are not directly applicable because the WR is a summary statistic derived from…

Methodology · Statistics 2026-02-20 Di Zhu , Yong Zang

Multivariate outcomes are common in pragmatic cluster randomized trials. While sample size calculation procedures for multivariate outcomes exist under parallel assignment, none have been developed for a stepped wedge design. In this…

Methodology · Statistics 2022-12-05 Kendra Davis-Plourde , Monica Taljaard , Fan Li

Predictive models are often required to produce reliable predictions under statistical conditions that are not matched to the training data. A common type of training-testing mismatch is covariate shift, where the conditional distribution…

Machine Learning · Computer Science 2025-01-22 Matteo Zecchin , Fredrik Hellström , Sangwoo Park , Shlomo Shamai , Osvaldo Simeone

While the inverse probability of treatment weighting (IPTW) is a commonly used approach for treatment comparisons in observational data, the resulting estimates may be subject to bias and excessively large variance when there is lack of…

Methodology · Statistics 2024-02-13 Zhiqiang Cao , Lama Ghazi , Claudia Mastrogiacomo , Laura Forastiere , F. Perry Wilson , Fan Li

Randomized Controlled Trials (RCTs) may suffer from limited scope. In particular, samples may be unrepresentative: some RCTs over- or under- sample individuals with certain characteristics compared to the target population, for which one…

Methodology · Statistics 2024-03-15 Bénédicte Colnet , Julie Josse , Gaël Varoquaux , Erwan Scornet

In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…

Methodology · Statistics 2020-10-02 Brian D. Segal , W. Katherine Tan

In stepped wedge cluster randomized trials (SW-CRTs), observations collected under the control condition are, on average, from an earlier time than observations collected under the intervention condition. In a cohort design, participants…

Methodology · Statistics 2023-02-23 Jale Basten , Katja Ickstadt , Nina Timmesfeld

Predicting risks of chronic diseases has become increasingly important in clinical practice. When a prediction model is developed in a given source cohort, there is often a great interest to apply the model to other cohorts. However, due to…

Methodology · Statistics 2020-03-05 Zheng Jiayin , Zheng Yingye , Hsu Li

Multi-arm trials are gaining interest in practice given the statistical and logistical advantages they can offer. The standard approach uses a fixed allocation ratio, but there is a call for making it adaptive and skewing the allocation of…

Methodology · Statistics 2026-01-16 Gianmarco Caruso , Pavel Mozgunov

Combining experimental and observational follow-up datasets has received a lot of attention lately. In a time-to-event setting, recent work has used medicare claims to extend the follow-up period for participants in a prostate cancer…

Methodology · Statistics 2022-04-12 Gang Cheng , Yen-Chi Chen , Joseph M. Unger , Cathee Till , Ying-Qi Zhao