Mitigating Operational Bias in Adaptive Design: A Regulatory Perspective

• Activity Number: 225
• Type: Topic Contributed
• Date/Time: Monday, August 4, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Section on Medical Devices and Diagnostics
• Author(s): Martin Ho*+
• Companies: FDA
• Keywords: adaptive design ; medical device ; operational bias ; DMC ; FDA ; CDRH

Abstract

Adaptive design has become increasingly popular among the medical devices trial community for its efficiency and flexibility. Through reviewing more than a decade of medical device submissions with varied indications and technologies, the Division of Biostatistics at FDA's Center for Devices and Radiological Health has accumulated substantial and wide-range experience in the evaluation and analysis of adaptive design trials. In this presentation, I will share my perspective as a reviewer on the operational aspect of adaptive designs and discuss some of the mitigation strategies. I will first lay out the fundamental principles we use to evaluate various types of adaptive designs and identify potential sources of operational bias. Next, I will discuss a few hypothetical yet typical examples to illustrate these principles and discuss some commonly used strategies for operational bias mitigation. Finally, I will conclude with some recommendations to mitigate operational bias of various adaptive designs.