Testing of evaluation bias for progression free survival endpoint in oncology clinical trials

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• 作者：Yan Sun ; Wenting Wu and Daniel Sargent
• 刊名：Statistics in Medicine
• 出版年：2016
• 出版时间：30 September 2016
• 年：2016
• 卷：35
• 期：22
• 页码：3923-3932
• 全文大小：260K
• ISSN：1097-0258

文摘

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