Cinzia Dello Russo1,2, Natalia Cappoli1, Pierluigi Navarra3,4. 1. Institute of Pharmacology, Catholic University Medical School, Largo F. Vito 1, 00168, Rome, Italy. 2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 3. Institute of Pharmacology, Catholic University Medical School, Largo F. Vito 1, 00168, Rome, Italy. pierluigi.navarra@unicatt.it. 4. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. pierluigi.navarra@unicatt.it.
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.
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.
Entities:
Keywords:
Blinded independent central review; Local evaluation; Oncology; Progression-free survival; Randomized controlled trial
Authors: Xinran Ma; Lawrence Bellomo; Ian Hooley; Tori Williams; Meghna Samant; Katherine Tan; Brian Segal; Ariel Bulua Bourla Journal: JAMA Netw Open Date: 2022-05-02