Clinical Trials: Innovative Design and Analysis Ideas for Improving Efficiency

• Activity Number: 591
• Type: Topic Contributed
• Date/Time: Thursday, August 7, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Yi Tsong*+
• Companies: FDA
• Keywords: TQT ; Crossover ; Parallel ; Hybrid design ; Adaptive

Abstract

A thorough QTc trial is typically designed to test for two set of hypotheses. The primary set of hypotheses is for demonstrating that the test treatment will not prolong QT interval in comparison to placebo. The second set of hypotheses is to demonstrate the assay sensitivity of the positive control treatment in the study population. The conventional designs of thorough QT studies are either parallel arms or crossover trials. Although the sample size requirements, the time points of analysis and durations of drug administration to reach steady stage are all different between the test and positive control treatments, the trials are often designed with equal study duration and sample size for the different treatment arms or periods. In order to reduce the number of subjects needed for the parallel arm or reduce the unneeded exposure to positive control treatment in the thorough QTc clinical trial, unconventional designs were proposed and used in the recent years. In this presentation, we review and discuss a few of the designs and propose some additional designs in the form of unbalanced, group sequential and adaptive designs with the objective to improve trial efficiency or to reduc