Table 1

Advantages of blinded independent centralized review and investigator-assessed progression-free survival 5

Advantages of blinded independent centralized review assessed progression-free survivalAdvantages of investigator-assessed progression-free survival
1.Reduces bias in assessment of progression-free survival as an endpoint in trials, particularly in trials with insufficient placebo blinding or for regulatory approvalsEvaluation is performed by clinicians and radiologists specialized in ovarian cancer
2.Progression-free survival determined by reviewer with no prior knowledge of the patient, thereby reducing the chance of inappropriately maintaining patients on promising investigational regimensInvestigators have access to a patient’s medical history and clinical data (eg, CA125 levels, prior therapies, all prior imaging data); this is particularly important in ovarian cancer as patients can often present with changes in imaging that do not necessarily meet RECIST v1.1 criteria
3.Blinded independent centralized review standardizes assessments across a trial and enhances consistency of image assessmentDecreased informative censoring (in cases of discordance between investigator and blinded independent centralized review assessed progressive disease)
4.Blinded independent centralized review is strongly encouraged for studies with progression-free survival or objective response rates as the primary endpoint, both by FDA guidance for industry on clinical trials endpoints for the approval for cancer drugs and biologics30 and by EMA guidelines on the methodological consideration for using progression-free survival or disease-free survival in confirmatory trials31 Reduced waiting time for patients when progressive disease is suspected
5.Overarching goal is to provide consistency in reader interpretation:
  • Limited number of pre-qualified reviewers and adjudicator(s) for reader discordance

  • Formal protocol-specific training (and re-training PRN) and imaging charter

  • Images presented in same manner to all reviewers, who have access to the same tools

  • Edit checks and audit trials

  • Scheduled periodic evaluation of reviewers via evaluation of reader variability rates and adjudicator agreement rates (or other metrics)

Radiological reviews by study investigators are considered a ‘real-world’ assessment of the clinical study results from a practitioner’s point of view
  • CA125, cancer antigen 125; EMA, European Medicines Agency; FDA, Food and Drug Administration; PRN, pro re nata; RECIST, Response Evaluation Criteria in Solid Tumors.