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Summary points: - This article considers the combination of two binary or two time-to-event endpoints to form the primary composite endpoint for leading a trial. - It discusses the relative efficiency of choosing a composite endpoint over…

Applications · Statistics 2020-01-13 Marta Bofill Roig , Jordi Cortés Martínez , Guadalupe Gómez Melis

For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints are widely chosen as the primary endpoint. Despite being commonly used, composite endpoints entail…

Methodology · Statistics 2022-09-27 Marta Bofill Roig , Guadalupe Gómez Melis , Martin Posch , Franz Koenig

Composite endpoints are widely used as primary endpoints in clinical trials. Designing trials with time-to-event endpoints can be particularly challenging because the proportional hazard assumption usually does not hold when using a…

Methodology · Statistics 2022-11-07 Jordi Cortés Martinez , Marta Bofill Roig , Guadalupe Gómez Melis

Mixed outcome endpoints that combine multiple continuous and discrete components to form co-primary, multiple primary or composite endpoints are often employed as primary outcome measures in clinical trials. There are many advantages to…

Methodology · Statistics 2019-12-12 Martina McMenamin , Jessica K. Barrett , Anna Berglind , James M. S. Wason

Composite endpoints are widely used in cardiovascular clinical trials to improve statistical efficiency while preserving clinical relevance. The Win Ratio (WR) measure and more general frameworks of Win Statistics have emerged as…

Methodology · Statistics 2025-11-24 Yunhan Mou , Fan Li , Denise Esserman , Yuan Huang

The choice of sample size in the context of co-primary endpoints for a randomised trial is discussed. Current guidance can leave endpoints with unequal marginal power. A method is provided to achieve equal marginal power by using the…

Methodology · Statistics 2026-02-23 Simon Bond

Composite endpoints are increasingly used in clinical trials to capture treatment effects across multiple or hierarchically ordered outcomes. Although inference procedures based on win statistics, such as the win ratio, win odds, and net…

Methodology · Statistics 2025-10-28 Xi Fang , Zhiqiang Cao , Fan Li

When developing a clinical prediction model, the sample size of the development dataset is a key consideration. Small sample sizes lead to greater concerns of overfitting, instability, poor performance and lack of fairness. Previous…

The increasing interest in subpopulation analysis has led to the development of various new trial designs and analysis methods in the fields of personalized medicine and targeted therapies. In this paper, subpopulations are defined in terms…

Methodology · Statistics 2020-12-01 Roland Gerard Gera , Tim Friede

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…

Simulation offers a simple and flexible way to estimate the power of a clinical trial when analytic formulae are not available. The computational burden of using simulation has, however, restricted its application to only the simplest of…

In survey sampling, calibration is a very popular tool used to make total estimators consistent with known totals of auxiliary variables and to reduce variance. When the number of auxiliary variables is large, calibration on all the…

Methodology · Statistics 2015-12-15 H. Cardot , C. Goga , M. -A Shehzad

Conventional methods for analyzing composite endpoints in clinical trials often only focus on the time to the first occurrence of all events in the composite. Therefore, they have inherent limitations because the individual patients' first…

Methodology · Statistics 2022-11-29 Jialu Wang , Yeh-Fong Chen , Thomas Gwise

We derive the sample size formulae for comparing two negative binomial rates based on both the relative and absolute rate difference metrics in noninferiority and equivalence trials with unequal follow-up times, and establish an approximate…

Methodology · Statistics 2017-05-24 Yongqiang Tang

This paper develops Bayesian sample size formulae for experiments comparing two groups. We assume the experimental data will be analysed in the Bayesian framework, where pre-experimental information from multiple sources can be represented…

Methodology · Statistics 2022-03-09 Haiyan Zheng , Thomas Jaki , James M. S. Wason

To estimate casual treatment effects, we propose a new matching approach based on the reduced covariates obtained from sufficient dimension reduction. Compared to the original covariates and the propensity score, which are commonly used for…

Methodology · Statistics 2017-02-03 Wei Luo , Yeying Zhu

Sequential Multiple-Assignment Randomized Trials (SMARTs) play an increasingly important role in psychological and behavioral health research. This experimental approach enables researchers to answer scientific questions about how to…

Methodology · Statistics 2023-06-21 John J. Dziak , Daniel Almirall , Walter Dempsey , Catherine Stanger , Inbal Nahum-Shani

Hierarchical composite endpoints, such as those analyzed using the Finkelstein-Schoenfeld (FS) statistic, are increasingly used in clinical trials for their ability to incorporate clinically prioritized outcomes. However, adaptive design…

Methodology · Statistics 2025-04-22 Krishna Padmanabhan , Cyrus Mehta

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

Estimation of crossed random effects models commonly requires computational costs that grow faster than linearly in the sample size $N$, often as fast as $\Omega(N^{3/2})$, making them unsuitable for large data sets. For non-Gaussian…

Methodology · Statistics 2025-05-01 Ruggero Bellio , Swarnadip Ghosh , Art B. Owen , Cristiano Varin
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