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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 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

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…

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…

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 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…

A common feature of many recent trials evaluating the effects of immunotherapy on survival is that non-proportional hazards can be anticipated at the design stage. This raises the possibility to use a statistical method tailored towards…

Applications · Statistics 2021-08-27 Dominic Magirr , José L. Jiménez

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…

Methodology · Statistics 2025-11-27 Luke Hagar , Shirin Golchi , Marina B. Klein

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

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

Count data and recurrent events in clinical trials, such as the number of lesions in magnetic resonance imaging in multiple sclerosis, the number of relapses in multiple sclerosis, the number of hospitalizations in heart failure, and the…

Applications · Statistics 2019-03-07 Tobias Mütze , Ekkehard Glimm , Heinz Schmidli , Tim Friede

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

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

Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have…

Methodology · Statistics 2017-10-11 Michael Grayling , James Wason , Adrian Mander

Widely used methods and software for group sequential tests of a null hypothesis of no treatment difference that allow for early stopping of a clinical trial depend primarily on the fact that sequentially-computed test statistics have the…

Methodology · Statistics 2025-06-19 Anastasios A. Tsiatis , Marie Davidian

While well-established methods for time-to-event data are available when the proportional hazards assumption holds, there is no consensus on the best approach under non-proportional hazards. A wide range of parametric and non-parametric…

In a group sequential clinical trial, accumulated data are analysed at numerous time-points in order to allow early decisions about a hypothesis of interest. These designs have historically been recommended for their ethical, administrative…

Computation · Statistics 2017-11-29 Michael Grayling , James Wason , Adrian Mander

Group sequential design (GSD) is widely used in clinical trials in which correlated tests of multiple hypotheses are used. Multiple primary objectives resulting in tests with known correlations include evaluating 1) multiple experimental…

Methodology · Statistics 2021-03-22 Keaven M. Anderson , Zifang Guo , Jing Zhao , Linda Z. Sun

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

In this paper we propose a Multiple kernel testing procedure to infer survival data when several factors (e.g. different treatment groups, gender, medical history) and their interaction are of interest simultaneously. Our method is able to…

Methodology · Statistics 2022-06-16 Marc Ditzhaus , Tamara Fernández , Nicolás Rivera
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