A Two-Tier Procedure for Designing and Analyzing Medical Device Trials Conducted in US and OUS Regions for Regulatory Decision Making

The number of clinical trials conducted simultaneously in the USA and outside of the US (OUS) for medical device development has been increasing over the last decade. However, the presence of inherent regional differences in treatment effects poses a great challenge to the US regulatory agency’s decision making. In this chapter, we propose a two-tier procedure for analyzing data from such trials for the US regulatory agency’s decision making, allowing treatment effects to vary from region to region. We differentiate direct evidence from supporting evidence while using both to exemplify the advantage of such trials for the US regulatory agency’s decision making. The contribution of the supporting evidence can be adjusted according to the expectation of the magnitude of regional differences and the statutory requirements in the USA. Examples are presented to illustrate the design and analysis based on our proposed procedure. Using the proposed two-tier procedure with an upfront explicit decision tree can increase the predictability and transparency of the regulatory decision making.