Blinded independent central review (Bicr) in new therapeutic lung cancer trials

Abstract

Background: Double reads in blinded independent central reviews (BICRs) are recommended to control the quality of trials but they are prone to discordances. We analyzed inter-reader discordances in a pool of lung cancer trials using RECIST 1.1. Methods: We analyzed six lung cancer BICR trials that included 1833 patients (10,684 time points) involving 17 radiologists. We analyzed the rate of discrepancy of each trial at the time-point and patient levels as well as testing inter-trial differences. The analysis of adjudication made it possible to compute the readers’ endorsement rates, the root causes of adjudications, and the proportions of “errors” versus “medically justifiable differences”. Results: The trials had significantly different discrepancy rates both at the time-point (average = 34.3%) and patient (average = 59.2%) levels. When considering only discrepancies for progressive disease, homogeneous discrepancy rates were found with an average of 32.9%, while readers’ endorsement rates ranged between 27.7% and 77.8%. Major causes of adjudication were different per trial, with medically justifiable differences being the most common, triggering 74.2% of total adjudications. Conclusions: We provide baseline performances for monitoring reader performance in trials with double reads. Intelligent reading system implementation along with appropriate reader training and monitoring are solutions that could mitigate a large portion of the commonly encountered reading errors.