Background: Blinded independent central review (BICR) of radiographic images is frequently conducted in oncology trials to address the potential bias of local evaluation (LE) of endpoints such as progression-free survival (PFS) and objective response rate (ORR). Given that BICR is a complex and costly process, we evaluated the agreement between LE- and BICR-based treatment effect results and the impact of BICR on regulatory decision-making.
Materials and methods: Meta-analyses were performed using hazard ratios (HRs) for PFS and odds ratios (ORs) for ORR from all randomized Roche-supported oncology clinical trials during 2006-2020 that had both LE and BICR results (49 studies with a total of over 32 000 patients).
Results: Overall, the evaluation bias of LE overestimating the treatment effect compared with BICR based on PFS was numerically small and not clinically meaningful, especially for double-blind studies (HR ratio between BICR and LE: 1.044). A larger bias is more likely to occur in studies with open-label design, smaller sample sizes, or an unequal randomization ratio. The majority (87%) of the PFS comparisons led to the same statistical inference by BICR and LE. For ORR, a high degree of agreement between BICR and LE results was also observed (OR ratio of 1.065), although the agreement was slightly lower than for PFS.
Conclusion: BICR did not notably impact the study interpretation nor drive the sponsor's regulatory submission decisions. Hence, if bias can be diminished by appropriate means, LE is deemed as reliable as BICR for certain study settings.
Keywords: blinded independent central review; local evaluation bias; meta-analysis; oncology clinical trial; progression-free survival; tumor response assessment.
© The Author(s) 2023. Published by Oxford University Press.