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We present several illustrations from completed clinical trials on a statistical approach that allows us to gain useful insights regarding the time dependency of treatment effects. Our approach leans on a simple proposition: all…

Methodology · Statistics 2024-07-29 Sean M. Devlin , John O'Quigley

The Proportional Hazards (PH) model is one of the most widely used models in survival analysis, typically assuming a log-linear relationship between covariates and the hazard function. However, in the context of spatial survival data, where…

Methodology · Statistics 2026-02-17 Lorenzo Tedesco , Francesco Finazzi

Composite endpoints are widely used as primary endpoints in clinical trials. Designing trials with time-to-event endpoints can be particularly challenging because the proportional hazard assumption usually does not hold when using a…

Methodology · Statistics 2022-11-07 Jordi Cortés Martinez , Marta Bofill Roig , Guadalupe Gómez Melis

Background: The hazard ratio of the Cox proportional hazards model is widely used in randomized controlled trials to assess treatment effects. However, two properties of the hazard ratio including the non-collapsibility and built-in…

Methodology · Statistics 2024-01-17 Helen Bian , Menglan Pang , Guanbo Wang , Zihang Lu

In oncology, conduct well-powered time-to-event randomized clinical trials may be challenging due to limited patietns number. Many designs for single-arm trials (SATs) have recently emerged as an alternative to overcome this issue. They…

Applications · Statistics 2026-04-10 Chloé Szurewsky , Guosheng Yin , Gwénaël Le Teuff

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

Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…

Applications · Statistics 2022-06-28 Guanhong Miao , Jason J. Z. Liao , Jing Yang , Keaven Anderson

The study of combinations of drugs/drug-schedules gained increasing attention in various therapeutic areas recently. In oncology, the aim of phase I combination clinical trial is to find the maximum tolerated combination (MTC). Many…

Methodology · Statistics 2025-05-09 Weishi Chen , Pavel Mozgunov

Background: Often when undertaking meta-analyses of time-to-event (TTE) outcomes, especially in a Health Technology Assessment context, a hazard ratio (HR) scale is used. However, issues arise when there is evidence of non-proportional…

Methodology · Statistics 2026-05-21 Rhiannon K Owen , Keith R Abrams

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

Among the challenges that the COVID-19 pandemic outbreak revealed is the problem to reduce the number of tests required for identifying the virus carriers in order to contain the viral spread while preserving the tests reliability. To cope…

Information Theory · Computer Science 2021-12-24 Catherine A. Haddad-Zaaknoon

Semi-parametric survival analysis methods like the Cox Proportional Hazards (CPH) regression (Cox, 1972) are a popular approach for survival analysis. These methods involve fitting of the log-proportional hazard as a function of the…

Machine Learning · Computer Science 2019-05-16 Chirag Nagpal , Rohan Sangave , Amit Chahar , Parth Shah , Artur Dubrawski , Bhiksha Raj

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

Competing risk data appear widely in modern biomedical research. Cause-specific hazard models are often used to deal with competing risk data in the past two decades. There is no current study on the kernel likelihood method for the…

Methodology · Statistics 2021-09-14 Xiaomeng Qi , Zhangsheng Yu

We propose a general methodology of sequential locally optimal design of experiments for explicit or implicit nonlinear models, as they abound in chemical engineering and, in particular, in vapor-liquid equilibrium modeling. As a sequential…

Optimization and Control · Mathematics 2024-03-15 Martin Bubel , Jochen Schmid , Volodymyr Kozachynskyi , Erik Esche , Michael Bortz

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

Methodology · Statistics 2014-02-12 Jay Bartroff , Tze Leung Lai , Balasubramanian Narasimhan

Scientists are attempting to use models of ever increasing complexity, especially in medicine, where gene-based diseases such as cancer require better modeling of cell regulation. Complex models suffer from uncertainty and experiments are…

Molecular Networks · Quantitative Biology 2018-06-01 Mahdi Imani , Roozbeh Dehghannasiri , Ulisses M. Braga-Neto , Edward R. Dougherty

High-dimensional data pose challenges in statistical learning and modeling. Sometimes the predictors can be naturally grouped where pursuing the between-group sparsity is desired. Collinearity may occur in real-world high-dimensional…

Machine Learning · Statistics 2011-11-11 Yiyuan She

Computerized adaptive testing is becoming increasingly popular due to advancement of modern computer technology. It differs from the conventional standardized testing in that the selection of test items is tailored to individual examinee's…

Statistics Theory · Mathematics 2009-06-11 Hua-Hua Chang , Zhiliang Ying

The Stepped Wedge Design (SWD) is a form of cluster randomized trial, usually comparing two treatments, which is divided into time periods and sequences, with clusters allocated to sequences. Typically all sequences start with the standard…

Methodology · Statistics 2020-11-06 John N. S. Matthews