A Prospective Bayesian Adaptive Trial with Hierarchical Borrowing from a Prior Single Arm Study

• Activity Number: 231
• Type: Topic Contributed
• Date/Time: Monday, August 10, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kristine Broglio* and Jason Connor and Scott M. Berry
• Companies: Berry Consultants and Berry Consultants and Berry Consultants
• Keywords: Bayesian ; adaptive ; augmented control ; historical control

Abstract

We describe a randomized controlled trial with hierarchical borrowing on the control arm for a cardiac device with primary efficacy and safety outcomes. This prospective 2-arm trial incorporates adaptive borrowing from a 1-armed trial of a similar device in Europe and interim analyses to stop the trial early for efficacy or futility. Using a Bayesian hierarchical model, the design is structured so if US data is similar to EU data, then more borrowing occurs, and less US data is needed. If the US and EU data are different, less borrowing will occur and the US trial will run to a larger sample size, providing independent data to substantiate the device's safety and effectiveness in the US patient population. We illustrate the trial, its operating characteristics and show how the actual trial progressed, stopping early for success, and leading to FDA approval.