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Related papers: Optimality of testing procedures for survival data

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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

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

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…

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

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

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

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

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

An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

In early-phase cancer clinical trials, the limited availability of data presents significant challenges in developing a framework to efficiently quantify treatment effectiveness. To address this, we propose a novel utility-based Bayesian…

Methodology · Statistics 2025-06-10 Saurabh Bhandari , Michael J. Daniels , Chenguang Wang

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

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

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change…

Methodology · Statistics 2018-12-11 Jose L Jimenez , Viktoriya Stalbovskaya , Byron Jones

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

In oncology the efficacy of novel therapeutics often differs across patient subgroups, and these variations are difficult to predict during the initial phases of the drug development process. The relation between the power of randomized…

Methodology · Statistics 2025-06-05 Boyu Ren , Federico Ferrari , Sandra Fortini , Steffen Ventz , Lorenzo Trippa

Nonlinear longitudinal proportional effect models have been proposed to improve power and provide direct estimates of the proportional treatment effect in randomized clinical trials. These models assume a fixed proportional treatment effect…

Methodology · Statistics 2026-01-23 Michael C. Donohue , Philip S. Insel , Oliver Langford

The log-rank test is most powerful under proportional hazards (PH). In practice, non-PH patterns are often observed in clinical trials, such as in immuno-oncology; therefore, alternative methods are needed to restore the efficiency of…

Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…

Methodology · Statistics 2025-09-10 James Salsbury , Jeremy Oakley , Steven Julious , Lisa Hampson

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

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…

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