Substantial Evidence: When is a Single Trial Sufficient for Approval and Promotion?

Abstract

The Federal Food, Drug, and Cosmetic Act provides FDA and sponsors with a statutory definition of “substantial evidence.” Most often drug effectiveness is established through the conduct of two adequate and well-controlled clinical trials (AWCTs), but there are situations where effectiveness can be sufficiently established through the conduct of a single AWCT. Some of these situations were detailed in FDA's 1998 guidance document, but there remains some uncertainty for sponsors in determining what cases might merit a single AWCT to meet the substantial evidence standard (depending on indication, drug class, etc). This article is meant as an aid for drug development teams, and regulatory professionals in particular, to navigate successfully through such questions of substantial evidence. We review some of the prerequisites and hurdles for drug approval based on FDA interpretation of substantial evidence standards. Finally, we will provide some suggestions to sponsors, in the context of case examples demons...