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The widely used proportional hazard assumption cannot be assessed reliably in small-scale clinical trials and might often in fact be unjustified, e.g. due to delayed treatment effects. An alternative to the hazard ratio as effect measure is…

Methodology · Statistics 2024-08-29 David Jesse , Cynthia Huber , Tim Friede

Statistical techniques are used in all branches of science to determine the feasibility of quantitative hypotheses. One of the most basic applications of statistical techniques in comparative analysis is the test of equality of two…

Methodology · Statistics 2018-05-01 Ayanendranath Basu , Abhijit Mandal , Nirian Martin , Leandro Pardo

We introduce a kernel-based goodness-of-fit test for censored data, where observations may be missing in random time intervals: a common occurrence in clinical trials and industrial life-testing. The test statistic is straightforward to…

Methodology · Statistics 2018-10-11 Tamara Fernández , Arthur Gretton

This article proposes omnibus portmanteau tests for contrasting adequacy of time series models. The test statistics are based on combining the autocorrelation function of the conditional residuals, the autocorrelation function of the…

Methodology · Statistics 2024-02-02 Esam Mahdi

When comparing multiple groups in clinical trials, we are not only interested in whether there is a difference between any groups but rather the location. Such research questions lead to testing multiple individual hypotheses. To control…

Survival analysis encompasses a broad range of methods for analyzing time-to-event data, with one key objective being the comparison of survival curves across groups. Traditional approaches for identifying clusters of survival curves often…

Methodology · Statistics 2025-12-19 Nora M. Villanueva , Marta Sestelo , Luis Meira-Machado

In heterogeneous cohorts and those where censoring by non-primary risks is informative many conventional survival analysis methods are not applicable; the proportional hazards assumption is usually violated at population level and the…

In comparative research on time-to-event data for two groups, when two survival curves cross each other, it may be difficult to use the log-rank test and hazard ratio (HR) to properly assess the treatment benefit. Our aim was to identify a…

Methodology · Statistics 2021-12-21 Xinghui Huang , Jingjing Lyu , Yawen Hou , Zheng Chen

Covariate-adaptive randomization is popular in clinical trials with sequentially arrived patients for balancing treatment assignments across prognostic factors which may have influence on the response. However, existing theory on tests for…

Statistics Theory · Mathematics 2020-08-25 Ting Ye , Jun Shao

A benefit of randomized experiments is that covariate distributions of treatment and control groups are balanced on average, resulting in simple unbiased estimators for treatment effects. However, it is possible that a particular…

Methodology · Statistics 2019-02-01 Zach Branson , Luke Miratrix

Recent observations, especially in cancer immunotherapy clinical trials with time-to-event outcomes, show that the commonly used proportial hazard assumption is often not justifiable, hampering an appropriate analyse of the data by hazard…

Methodology · Statistics 2021-02-23 Marc Ditzhaus , Menggang Yu , Jin Xu

Factorial survival designs with right-censored observations are commonly inferred by Cox regression and explained by means of hazard ratios. However, in case of non-proportional hazards, their interpretation can become cumbersome;…

Methodology · Statistics 2020-06-26 Marc Ditzhaus , Dennis Dobler , Markus Pauly

Several methods in survival analysis are based on the proportional hazards assumption. However, this assumption is very restrictive and often not justifiable in practice. Therefore, effect estimands that do not rely on the proportional…

Methodology · Statistics 2024-03-20 Merle Munko , Marc Ditzhaus , Dennis Dobler , Jon Genuneit

Single-arm studies in the early development phases of new treatments are not uncommon in the context of rare diseases or in paediatrics. If an assessment of efficacy is to be made at the end of such a study, the observed endpoints can be…

Methodology · Statistics 2026-03-02 Moritz Fabian Danzer , Rene Schmidt

In confirmatory cancer clinical trials, overall survival (OS) is normally a primary endpoint in the intention-to-treat (ITT) analysis under regulatory standards. After the tumor progresses, it is common that patients allocated to the…

Methodology · Statistics 2022-01-19 José L. Jiménez , Julia Niewczas , Alexander Bore , Carl-Fredrik Burman

In survival studies, classical inferences for left-truncated data require quasi-independence, a property that the joint density of truncation time and failure time is factorizable into their marginal densities in the observable region. The…

Methodology · Statistics 2019-04-16 Young-Geun Choi , Wei-Yann Tsai , Myunghee Cho Paik

We propose a class of locally and asymptotically optimal tests, based on multivariate ranks and signs for the homogeneity of scatter matrices in $m$ elliptical populations. Contrary to the existing parametric procedures, these tests remain…

Statistics Theory · Mathematics 2008-12-18 Marc Hallin , Davy Paindaveine

Restricted mean survival time (RMST) offers a compelling nonparametric alternative to hazard ratios for right-censored time-to-event data, particularly when the proportional hazards assumption is violated. By capturing the total event-free…

Methodology · Statistics 2025-01-28 Jinghao Sun , Douglas E. Schaubel , Eric J. Tchetgen Tchetgen

IMPORTANCE: Time-to-event outcomes are commonly used in clinical trials and biomarker discovery studies and have been primarily analyzed using Cox proportional hazards models. But it's unclear which statistical models should be recommended…

Methodology · Statistics 2022-08-23 Rong Lu

Delayed separation of survival curves is a common occurrence in confirmatory studies in immuno-oncology. Many novel statistical methods that aim to efficiently capture potential long-term survival improvements have been proposed in recent…

Methodology · Statistics 2022-01-26 Dominic Magirr , José L. Jiménez