Evaluation of Discordance Measures in Oncology Studies with Blinded Independent Central Review of Progression-Free Survival Using an Observational Error Model

Abstract

To confirm results obtained from local evaluation at investigational centers, many oncology studies utilize blinded independent central review (BICR) to make assessments of the primary endpoint, progression-free survival (PFS). The comparison of data often leads to large discordances between these observations, casting doubt on the reliability of the estimated treatment effects from these trials. Here we propose new statistics to measure discordance and evaluate their utility to detect bias in the local evaluation of progression relative to the standard measures of discordance. A new observational error model is proposed that can be used to describe the discordance in patient assessments between multiple readers.

Key Words:

• Blinded independent central review
• Discordance
• Progression-free survival

ACKNOWLEDGMENTS

The authors acknowledge the contributions of the following: Will Bushnell, GSK; Nicole Blackman, GSK; Lauren McCann, GSK; Andy Stone, AstraZeneca.

Notes

Note. a ₁, number of agreements on timing and occurrence of PD; a ₂, number of times LE declares PD later than BICR; a ₃, number of times LE declares PD earlier than BICR; and n = a + b + c + d.