Evaluation of Blinded Independent Central Review of Tumor Progression in Oncology Clinical Trials: A Meta-analysis

Abstract

Use of blinded independent central review (BICR) has become more common in oncology phase 3 trials as progression-free survival (PFS) has been increasingly used as an endpoint for regulatory approval. Since PFS is primarily a radiographic endpoint, BICR has been implemented to assess and reduce potential bias in the local evaluation (LE) of PFS. Recent publications note an agreement between LE and BICR of the ultimate reported PFS treatment effect, which questions the need for costly and time-consuming complete-case BICR of PFS. A meta-analysis was conducted to systematically evaluate the relationship between BICR- and LE-assessed PFS based on FDA's regulatory experience from 2005 to present. Our results support the claim that a complete review of all radiographs by BICR may not be necessary for oncology trials, and alternative methods should be explored to evaluate bias. One potential alternative is to use BICR as an audit tool to detect evaluation bias in LE assessments.