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In two harmonized efficacy studies to prevent HIV infection through multiple infusions of the monoclonal antibody VRC01, a key objective is to evaluate whether the serum concentration of VRC01, which changes cyclically over time along with…

Methodology · Statistics 2018-01-26 Yunda Huang , Yuanyuan Zhang , Zong Zhang , Peter B. Gilbert

The Cox proportional hazards model, commonly used in clinical trials, assumes proportional hazards. However, it does not hold when, for example, there is a delayed onset of the treatment effect. In such a situation, an acute change in the…

Methodology · Statistics 2022-04-22 Ryoto Ozaki , Yoshiyuki Ninomiya

The advent and subsequent widespread availability of preventive vaccines has altered the course of public health over the past century. Despite this success, effective vaccines to prevent many high-burden diseases, including HIV, have been…

The ratio of the hazard functions of two populations or two strata of a single population plays an important role in time-to-event analysis. Cox regression is commonly used to estimate the hazard ratio under the assumption that it is…

Methodology · Statistics 2022-07-13 Yujian Wu , Ted Westling

The proportional hazards assumption in the commonly used Cox model for censored failure time data is often violated in scientific studies. Yang and Prentice (2005) proposed a novel semiparametric two-sample model that includes the…

Methodology · Statistics 2012-06-06 Guoqing Diao , Donglin Zeng , Song Yang

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

In observational studies with survival or time-to-event outcomes, a propensity score weighted marginal Cox proportional hazard model with the treatment variable as the only predictor is commonly used to estimate the causal marginal hazard…

Methodology · Statistics 2026-02-02 Zixian Zhao , Chengxin Yang , Fan Li

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

From an optimizer's perspective, achieving the global optimum for a general nonconvex problem is often provably NP-hard using the classical worst-case analysis. In the case of Cox's proportional hazards model, by taking its statistical…

Statistics Theory · Mathematics 2021-07-07 Jianqing Fan , Wenyan Gong , Qiang Sun

This paper proposes nonparametric two-sample tests for the direct comparison of the probabilities of a particular transition between states of a continuous time nonhomogeneous Markov process with a finite state space. The proposed tests are…

Methodology · Statistics 2020-02-24 Giorgos Bakoyannis

In many biomedical applications, outcome is measured as a ``time-to-event'' (eg. disease progression or death). To assess the connection between features of a patient and this outcome, it is common to assume a proportional hazards model,…

Statistics Theory · Mathematics 2020-08-11 Aliasghar Tarkhan , Noah Simon

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

Survival models are a popular tool for the analysis of time to event data with applications in medicine, engineering, economics, and many more. Advances like the Cox proportional hazard model have enabled researchers to better describe…

Machine Learning · Statistics 2021-02-16 Stefan Groha , Sebastian M Schmon , Alexander Gusev

Non-proportional hazards data are routinely encountered in randomized clinical trials. In such cases, classic Cox proportional hazards model can suffer from severe power loss, with difficulty in interpretation of the estimated hazard ratio…

Methodology · Statistics 2023-12-29 Hong Zhang , Qing Li , Devan V. Mehrotra , Judong Shen

Time-to-event endpoints show an increasing popularity in phase II cancer trials. The standard statistical tool for such one-armed survival trials is the one-sample log-rank test. Its distributional properties are commonly derived in the…

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

Analysing subgroups defined by biomarkers is of increasing importance in clinical research. In some situations the biomarker is subject to misclassification error, meaning the true subgroups are identified with imperfect sensitivity and…

Methodology · Statistics 2018-01-16 Fang Wan , Andrew C. Titman , Thomas F. Jaki

Prevalent cohort sampling is commonly used to study the natural history of a disease when the disease is rare or it usually takes a long time to observe the failure event. It is known, however, that the collected sample in this situation is…

Methodology · Statistics 2022-09-05 Omidali Aghababaei Jazi

The hazard ratio from the Cox proportional hazards model is a ubiquitous summary of treatment effect. However, when hazards are non-proportional, the hazard ratio can lose a stable causal interpretation and become study-dependent because it…

Methodology · Statistics 2026-02-17 Xiang Meng , Lu Tian , Kenneth Kehl , Hajime Uno

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

We present a method for estimating the correlation between log-rank test statistics evaluating separate null hypotheses for two time-to-event endpoints. The correlation is estimated using subject-level data by a non-parametric approach…

Methodology · Statistics 2026-01-07 Anne Lyngholm Soerensen , Paul Blanche , Henrik Ravn , Christian Pipper