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

Yan Sun, Wenting Wu, Daniel Sargent

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)3923-3932
Number of pages10
JournalStatistics in Medicine
Volume35
Issue number22
DOIs
StatePublished - Sep 30 2016

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Keywords

  • hypothesis test
  • independent review
  • progression free survival

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability
  • Medicine(all)

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