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In this paper we consider a group sequentially monitored trial on a survival endpoint, monitored using a weighted log-rank (WLR) statistic with deterministic weight function. We introduce a summary statistic in the form of a weighted…

Methodology · Statistics 2017-11-30 Grant Izmirlian

Survival time is the primary endpoint of many randomized controlled trials, and a treatment effect is typically quantified by the hazard ratio under the assumption of proportional hazards. Awareness is increasing that in many settings this…

Methodology · Statistics 2023-10-04 Robin Ristl , Heiko Götte , Armin Schüler , Martin Posch , Franz König

Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the…

Methodology · Statistics 2024-03-19 Miki Horiguchi , Lu Tian , Kenneth L. Kehl , Hajime Uno

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

For the analysis of time-to-event data, frequently used methods such as the log-rank test or the Cox proportional hazards model are based on the proportional hazards assumption, which is often debatable. Although a wide range of parametric…

Non-proportional hazards (NPH) have been observed recently in many immuno-oncology clinical trials. Weighted log-rank tests (WLRT) with suitably chosen weights can be used to improve the power of detecting the difference of the two survival…

Methodology · Statistics 2023-01-18 Lili Wang , Xiaodong Luo , Cheng Zheng

We propose a method for comparing survival data based on the higher criticism of p-values obtained from multiple exact hypergeometric tests. The method accommodates non-informative right-censorship and is sensitive to hazard differences in…

Statistics Theory · Mathematics 2025-10-28 Alon Kipnis , Ben Galili , Zohar Yakhini

The conventional nonparametric tests in survival analysis, such as the log-rank test, assess the null hypothesis that the hazards are equal at all times. However, hazards are hard to interpret causally, and other null hypotheses are more…

Methodology · Statistics 2019-01-29 Mats Julius Stensrud , Kjetil Røysland , Pål Christie Ryalen

We revisit the question of what randomization ratio (RR) maximizes power of the logrank test in event-driven survival trials under proportional hazards (PH). By comparing three approximations of the logrank test (Schoenfeld, Freedman,…

Methodology · Statistics 2025-05-20 Godwin Yung , Kaspar Rufibach , Marcel Wolbers , Ray Lin , Yi Liu

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

In clinical and epidemiological studies, hazard ratios are often applied to compare treatment effects between two groups for survival data. For competing risks data, the corresponding quantities of interest are cause-specific hazard ratios…

Applications · Statistics 2021-12-21 Hongji Wu , Hao Yuan , Zijing Yang , Yawen Hou , Zheng Chen

Restricted mean survival time (RMST) is gaining attention as a measure to quantify the treatment effect on survival outcomes in randomized clinical trials. Several methods to determine sample size based on the RMST-based tests have been…

Methodology · Statistics 2022-12-19 Satoshi Hattori , Hajime Uno

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

One of the most common ways researchers compare survival outcomes across treatments when confounding is present is using Cox regression. This model is limited by its underlying assumption of proportional hazards; in some cases, substantial…

Applications · Statistics 2021-02-02 Elizabeth A. Handorf , Marc Smaldone , Sujana Movva , Nandita Mitra

Weighted logrank tests are a popular tool for analyzing right censored survival data from two independent samples. Each of these tests is optimal against a certain hazard alternative, for example the classical logrank test for proportional…

Statistics Theory · Mathematics 2018-07-17 Marc Ditzhaus , Sarah Friedrich

It is of special importance in the clinical trial to compare survival times between the treatment group and the control group. Propensity score methods with a logistic regression model are often used to reduce the effects of confounders.…

Statistics Theory · Mathematics 2024-12-03 Tomoya Baba , Nakahiro Yoshida

The use of the non-parametric Restricted Mean Survival Time endpoint (RMST) has grown in popularity as trialists look to analyse time-to-event outcomes without the restrictions of the proportional hazards assumption. In this paper, we…

Methodology · Statistics 2023-11-06 Emily Alger , David S. Robertson , Abigail J. Burdon

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

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…

Investigating the causal relationship between exposure and the time-to-event outcome is an important topic in biomedical research. Previous literature has discussed the potential issues of using the hazard ratio as a marginal causal effect…

Methodology · Statistics 2022-05-05 Zihan Lin , Ai Ni , Bo Lu