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Related papers: Alternative Analysis Methods for Time to Event End…

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While well-established methods for time-to-event data are available when the proportional hazards assumption holds, there is no consensus on the best inferential approach under non-proportional hazards (NPH). However, a wide range of…

We conducted a systematic comparison of statistical methods used for the analysis of time-to-event outcomes under various proportional and nonproportional hazard (NPH) scenarios. Our study used data from recently published oncology trials…

Applications · Statistics 2025-02-12 Xinyu Zhang , Erich J. Greene , Ondrej Blaha , Wei Wei

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. With the emergence of immunotherapy and novel targeted therapies, departure from the proportional hazard assumption is not rare in…

Methodology · Statistics 2020-08-27 José L. Jiménez

The log-rank test and the Cox proportional hazards model are commonly used to compare time-to-event data in clinical trials, as they are most powerful under proportional hazards. But there is a loss of power if this assumption is violated,…

Methodology · Statistics 2024-02-14 Jonas Brugger , Tim Friede , Florian Klinglmüller , Martin Posch , Robin Ristl , Franz König

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…

Background: For RCTs with time-to-event endpoints, proportional hazard (PH) models are typically used to estimate treatment effects and logrank tests are commonly used for hypothesis testing. There is growing support for replacing this…

Methodology · Statistics 2024-12-10 Dominic Magirr , Craig Wang , Xinlei Deng , Tim Morris , Mark Baillie

Loss of power and clear description of treatment differences are key issues in designing and analyzing a clinical trial where non-proportional hazard is a possibility. A log-rank test may be very inefficient and interpretation of the hazard…

Applications · Statistics 2021-01-13 Satrajit Roychoudhury , Keaven M Anderson , Jiabu Ye , Pralay Mukhopadhyay

The introduction of checkpoint inhibitors in immuno-oncology has raised questions about the suitability of the log-rank test as the default primary analysis method in confirmatory studies, particularly when survival curves exhibit…

Methodology · Statistics 2024-12-20 Dominic Magirr , Fredrik Öhrn

The classical approach to analyze time-to-event data, e.g. in clinical trials, is to fit Kaplan-Meier curves yielding the treatment effect as the hazard ratio between treatment groups. Afterwards commonly a log-rank test is performed in…

Methodology · Statistics 2020-09-16 Kathrin Möllenhoff , Achim Tresch

When planning a clinical trial for a time-to-event endpoint, we require an estimated effect size and need to consider the type of effect. Usually, an effect of proportional hazards is assumed with the hazard ratio as the corresponding…

Methodology · Statistics 2026-03-02 Moritz Fabian Danzer , Ina Dormuth

Studies to compare the survival of two or more groups using time-to-event data are of high importance in medical research. The gold standard is the log-rank test, which is optimal under proportional hazards. As the latter is no simple…

Methodology · Statistics 2022-10-25 Ina Dormuth , Tiantian Liu , Jin Xu , Markus Pauly , Marc Ditzhaus

In practice, the logrank test is the most widely used method for testing the equality of survival distributions. It is the optimal method under the proportional hazard assumption. However, since non-proportional hazards are often…

Methodology · Statistics 2021-10-11 Huan Cheng , Jianghua He

What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has…

Methodology · Statistics 2023-04-18 José L. Jiménez , Isobel Barrott , Francesca Gasperoni , Dominic Magirr

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

Non-proportional hazards (NPH) are often observed in clinical trials with time-to-event endpoints. A common example is a long-term clinical trial with a delayed treatment effect in immunotherapy for cancer. When designing clinical trials…

Methodology · Statistics 2025-09-18 Yujie Zhao , Yilong Zhang , Larry Leon , Keaven M. Anderson

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

Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…

Statistics Theory · Mathematics 2020-05-28 Andrea Arfé , Brian Alexander , Lorenzo Trippa

In confirmatory clinical trials, survival outcomes are frequently studied and interim analyses for efficacy and/or futility are often desirable. Methods such as the log rank test and Cox regression model are commonly used to compare…

Methodology · Statistics 2024-03-27 Peter Zhang , Brent Logan , Michael Martens

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

Time-to-event data with long-term survivors (L-TS), subjects who never experience the event, have been reported in multiple areas of oncology as therapies have improved. Conventional two-sample tests ignore L-TS, but alternatives have been…

Methodology · Statistics 2026-05-06 Yu Bi , Durbadal Ghosh , Subodh Selukar
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