Sequential design for clinical trials evaluating a prosthetic heart valve.

Abstract

Clinical trials involving prosthetic heart valves are typically based on a set of objective performance criteria for certain late adverse event rates. Typically, these trials require 800 patient-years of data to be collected to provide 80% power while maintaining the type I error at the 0.05 level. This work presents a sequential design alternative to the standard objective performance criteria trial that allows for the possibility of stopping the trial early. Logistical issues regarding these designs are considered, and power calculations are provided that investigate the probability of early stopping if the prosthetic valve exceeds expectations with respect to the objective performance criteria end points. Designs exist that provide at least 50% power at the interim look and 80% overall power under the alternative hypothesis. If the prosthetic valve performs better than expected, the interim power may exceed 80%. The proposed sequential designs can reduce the time required to bring a prosthetic heart valve to market, helping to ensure that patients and clinicians have access to the latest devices in shorter time.