# Concordance in assessments between investigators and blinded independent central review (BICR) in hematology oncology clinical trials: a meta-analysis

## TL;DR

This study finds that in hematology cancer trials, investigators and blinded reviewers agree closely on results, suggesting BICR may not be as necessary as in other cancer types.

## Contribution

The study is the first meta-analysis to evaluate BICR-investigator concordance specifically in hematology trials.

## Key findings

- Pooled hazard ratio ratio for PFS was 0.96, indicating strong agreement between investigators and BICR.
- Pooled odds ratio ratio for ORR was 0.99, showing minimal difference in response rate assessments.
- Subgroup analyses across cancer types and trial sizes consistently showed high concordance.

## Abstract

Blinded independent central review (BICR) mitigates assessment bias in oncology trials but imposes significant operational burdens. Its value in hematologic malignancies—where multimodal response criteria reduce reliance on subjective imaging assessments compared to solid tumors—remains unestablished. This meta-analysis evaluates BICR-investigator concordance specifically in hematology trials.

We systematically identified Phase II/III hematology trials (2014-2024) reporting progression-free survival (PFS) and/or objective response rate (ORR) assessments by both investigators and BICR from PubMed. Agreement was quantified using Pearson/Spearman correlation, pooled hazard ratio ratio (HRR, HRINV/HRBICR) for PFS, and odds ratio ratio for ORR (OddsRR, ORINV/ORBICR). We also analyzed the odds ratio for ORR for single arms (OddsINV/OddsBICR). Subgroup analyses assessed the impact of masking, cancer type based on imaging dependence, and sample size.

Data from 70 studies (37 PFS comparisons; 23 ORR comparisons; 29 single-arm ORR) were analyzed. For PFS, the pooled HRR was 0.96 (95% CI: 0.89, 1.03), with perfect agreement in statistical significance (Cohen’s kappa = 1). For ORR, the pooled OddsRR was 0.99 (95% CI: 0.85, 1.14). Single-arm trials showed minimal odds difference between assessors (OR = 1.02, 95% CI: 0.90, 1.17). Subgroup analyses (masking, cancer type, sample size) consistently showed high agreement.

Investigator and BICR assessments demonstrated substantial concordance in hematology trials. The common applications of BICR in registration trials provide minimal added value for primary endpoint validation in this setting. We recommend prioritizing investigator training and standardized criteria to optimize resource allocation.