A Simulation Study to Evaluate Accuracy and Precision of Blinded Independent Central Reviews (BICR) on Progression-Free Survival in Cancer Clinical Trials

• Activity Number: 26
• Type: Topic Contributed
• Date/Time: Sunday, August 4, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Imaging
• Author(s): Fenghai Duan*+ and Richard Walovitch and Vincent Girardi
• Companies: Brown University and WorldCare Clinical, LLC and WorldCare Clinical, LLC
• Keywords: accuracy ; precision ; blinded independent central reviews (BICR) ; progression-free survival (PFS) ; cancer ; biostatistics

Abstract

Background: A BICR is often recommended in open labeled trials and has the potential to also increase the accuracy and precision (A & P) of a subjective assessment. To understand its magnitude, a statistical model was developed to determine the effect on sample size and trial cost in progression-free survival (PSF) trials. Method: PFS times were simulated based on a tumor growth model using a median 180 days in the control arm; the treatment arm varied according to hazard ratios (HR) from 0.7-0.85. False positives were added for A and a log normal distribution of measurement error was used for P. Local evaluation (LE A=70% & P= 76%) were compared to different BICR paradigms with varying A &P measurement error A=70,90% & P=76, 80, 88%. Results: Compared to LE, all BICR paradigms decreased overall trial cost by $0.00037-2.7x107 and sample sizes by 12-435 with effect magnitude being greatest at higher HRs, A & P. Conclusion: Our study indicates that for trials with PFS based on a radiological assessment, BICR can be a cost effective strategy by decreasing sample sizes and trial costs.