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

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

• Publication year

  2025

• Venue

  The Oncologist

• Publication date

  2025-11-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1093/oncolo/oyaf375PMID 41206920PMCID 12622372
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Assessment of Objective Response Rate by Investigator vs. Blinded Independent Central Review in Pivotal Trials of Oncology Drugs for Solid Tumor Indications

  2025cited by this paper
• Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis.

  2024cited by this paper
• Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis.

  2023cited by this paper
• Meta-Analysis of 49 Roche Oncology Trials Comparing Blinded Independent Central Review (BICR) and Local Evaluation to Assess the Value of BICR

  2023cited by this paper
• Appropriate statistical methods are available to handle biases encountered in blinded, independent, central review (BICR) determined progression-free survival.

  2019cited by this paper
• RoB 2: a revised tool for assessing risk of bias in randomised trials

  2019cited by this paper
• Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour

  2018cited by this paper
• International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

  2016cited by this paper
• Response assessment in lymphoma: Concordance between independent central review and local evaluation in a clinical trial setting

  2016cited by this paper
• Bias in progression‐free survival analysis due to intermittent assessment of progression

  2015cited by this paper
• Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.

  2014cited by this paper
• Evaluation of Blinded Independent Central Review of Tumor Progression in Oncology Clinical Trials: A Meta-analysis

  2013cited by this paper
• Is it time to abandon complete blinded independent central radiological evaluation of progression in registration trials?

  2011cited by this paper
• Blinded independent central review of progression in cancer clinical trials: results from a meta-analysis.

  2011cited by this paper
• Research outcomes and recommendations for the assessment of progression in cancer clinical trials from a PhRMA working group.

  2011cited by this paper
• New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

  2009cited by this paper
• Blinded independent central review of progression-free survival in phase III clinical trials: important design element or unnecessary expense?

  2008cited by this paper
• When you look matters: the effect of assessment schedule on progression-free survival.

  2007cited by this paper
• Indirect comparisons of competing interventions.

  2005cited by this paper

• No citing papers are available for this paper.