Testing of evaluation bias for progression free survival endpoint in oncology clinical trials. (18th April 2016)

• Record Type: Journal Article
• Authors: Sun, Yan; Wu, Wenting; Sargent, Daniel
• Is Part Of: Statistics in medicine. Volume 35:Number 22(2016)
• Page Start: 3923
• Page End: 3932
• Publication Date: 2016-04-18
• Subjects: progression free survival -- independent review -- hypothesis test; Medical statistics -- Periodicals; Statistique médicale -- Périodiques; Statistiques médicales -- Périodiques; 610.727
• DOI: 10.1002/sim.6963
• Languages: English
• ISSNs: 0277-6715

Abstract

Abstract : Progression‐free survival is an increasingly popular end point in oncology clinical trials. A complete blinded independent central review (BICR) is often required by regulators in an attempt to reduce the bias in progression‐free survival (PFS) assessment. In this paper, we propose a new methodology that uses a sample‐based BICR as an audit tool to decide whether a complete BICR is needed. More specifically, we propose a new index, the differential risk, to measure the reading discordance pattern, and develop a corresponding hypothesis testing procedure to decide whether the bias in local evaluation is acceptable. Simulation results demonstrate that our new index is sensitive to the change of discordance pattern; type I error is well controlled in the hypothesis testing procedure, and the calculated sample size provides the desired power. Copyright © 2016 John Wiley & Sons, Ltd.