title: Testing of evaluation bias for progression free survival endpoint in oncology clinical trials.
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.
authors.affiliation: University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL, 60607, U.S.A.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: AstraZeneca, 200 ORD, Gaithersburg, MD, 20877, U.S.A.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, U.S.A.
authors.forename: Daniel
authors.identifier: 0000-0002-2684-4741
authors.initials: D
authors.lastname: Sargent
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D008495:Medical Oncology; D009369:Neoplasms / Q000628:therapy*; D018401:Sample Size
keywords: hypothesis test; independent review; progression free survival