A comparison between the assessments of progression-free survival by local investigators versus blinded independent central reviews in phase III oncology trials.

ABSTRACT

PURPOSE: In this study, we compared the assessments of progression-free survival (PFS) carried out by the local investigator or by a blinded independent central review in the framework of phase III registration randomized controlled trials (RCT) in oncology. METHODS: We carried out a search in the clinicatrials.gov database, looking at the RCTs reporting the results of both independently assessed and investigator-assessed PFS. The hazard ratios (HRs) of investigator-assessed PFS and independently assessed PFS were recorded, and a discrepancy index was obtained by calculating the ratio of their respective HRs. Moreover, we investigated possible factors of discrepancy by analyzing the trials in different groups (by year, by tumor type, by drug type, by study design). RESULTS: We analyzed 28 RCTs meeting the search criteria. The estimated mean discrepancy index was 0.98 (confidence interval 0.927-1.032 (n = 32)). Subgroup analysis showed that the confidence intervals in all cases included the value 1, except in the subgroup of studies started in the period 2003-2006. CONCLUSION: In phase III oncology trials, we found no significant differences between the hazard ratios estimated by local investigators and those estimated by blinded independent central reviews. A relatively higher variability, in terms of large CI, was found in trials with biological agents.