Quantum of Effectiveness Evidence in FDA’s Approval of Orphan Drugs

One of the key underlying issues facing the development of all drugs, and particularly orphan drugs, is what kind of evidence the Food and Drug Administration (FDA) requires for approval. The Federal Food, Drug, and Cosmetic [FD&C] Act provides that for FDA to grant approval for a new drug, there must be “substantial evidence” of effectiveness derived from “adequate and well-controlled investigations.” This language, which dates from 1962, provides leeway for FDA medical reviewers to make judgments as to what constitutes “substantial evidence” of a drug’s effectiveness, that is, of its benefit to patients.