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.
Original language | English (US) |
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Pages (from-to) | 3923-3932 |
Number of pages | 10 |
Journal | Statistics in Medicine |
Volume | 35 |
Issue number | 22 |
DOIs | |
State | Published - Sep 30 2016 |
Keywords
- hypothesis test
- independent review
- progression free survival
ASJC Scopus subject areas
- Epidemiology
- Statistics and Probability