Testing of evaluation bias for progression free survival endpoint in oncology clinical trials |
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Authors: | Yan Sun Wenting Wu Daniel Sargent |
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Affiliation: | 1. University of Illinois at Chicago, Chicago, IL, U.S.A.;2. AstraZeneca, Gaithersburg, MD, U.S.A.;3. Mayo Clinic, Rochester, MN, U.S.A. |
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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. |
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Keywords: | progression free survival independent review hypothesis test |
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