Application of Value Frameworks to the Design of Clinical Trials: the Canadian Cancer Trials Group Experience.

BACKGROUND Use of value framework thresholds in the design of clinical trials may increase the proportion of randomized controlled trials (RCTs) that identify clinically meaningful advances for patients. Existing frameworks have not been applied to the research output of a cooperative cancer trials group. We apply value frameworks to the RCT output of the Canadian Cancer Trials Group (CCTG). METHODS Statistical design, study characteristics, and results of all published phase III trials of CCTG were abstracted. We applied the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and American Society of Clinical Oncology Net Health Benefit (ASCO-NHB) to study results and the statistical power calculations to identify the proportion of all trials that were designed to detect a substantial clinical benefit. RESULTS During 1979-2017, CCTG published 113 phase III trials; 52.2% (59 of 113) of these trials were positive. Half (50.4%, 57 of 113) of trials were conducted in the palliative setting. In 37.2% (42 of 113) of trials the primary endpoint was overall survival; DFS or PFS was used in 38.9% (44 of 113) of trials. The ESMO-MCBS could be applied to the power calculation for 69 trials; 73.9% (51 of 69) of these trials were designed to detect an effect size that could meet ESMO-MCBS thresholds for substantial benefit. Among the 51 positive trials for which the ESMO-MCBS could be applied, 41.1% (21 of 51) met thresholds for substantial benefit. CONCLUSIONS Most CCTG phase III trials were designed to detect clinically meaningful differences in outcome, although less than half of positive trials met the threshold for substantial benefit. Application of value frameworks to the design of clinical trials is practical and may improve research efficiency and treatment options for patients.