Challenges with the ODAC-proposed independent audit of site investigator assessments.

Abstract

e22161 Background: The ODAC (Oncologic Drug Advisory Committee) Meeting, July 24th, 2012, on “Evaluation of Radiologic Review of Progression-free Survival in Non-hematologic Malignancies” discussed the merits of implementing an audit process of the investigator assessments in certain oncology trials with PFS endpoint instead of a full Blinded Independent Central Review (BICR) of all cases. The discussion centered around two potential methods (Dodd et al., 2008, 2011 and Amit et al., 2011) – their methods aimed to reduce the risk of informative censoring based on site central discordance, streamline trial conduct and provide cost savings. Both methods provide novel and interesting approaches. However, based on logistical and especially statistical challenges we found that both proposed methods in their current form can not achieve either goal of reducing cost, complexity, time and data censoring challenges inherent in the BICR process. Methods: This paper criticially evaluate the proposed methods and challenge the proposed processes and provide detailed explanations to obstacles inherent logistically, timewise, statistically, operationally. Results: Both of the proposed methods increase the complexity of conducting Oncology trials. As such the study duration will not be shortened but rather extended in certain scenarios. The statistical consequences of a discrepancy rate between Local Evaluations (LE) and BICR are not fully foreseeable and not defined. Operationally, both sponsor and imaging CRO need to implement new and forego well established processes, increasing risk, complexity and the chance for errors. Conclusions: This paper gives examples why the proposed methods are not suitable in their current form to be implemented in Oncology trials and rather put sponsors and study data at risk.