EVIDENCE AND EXTRAPOLATION: MECHANISMS FOR REGULATING OFF-LABEL USES OF DRUGS AND DEVICES

Abstract

A recurring, foundational issue for evidence-based regulation is deciding whether to extend governmental approval from an existing use with sufficient current evidence of safety and efficacy to a novel use for which such evidence is currently lacking. This "extrapolation" issue arises in the medicines context when an approved drug or device that is already being marketed is being considered (1) for new conditions (such as off-label diagnostic categories), (2) for new patients (such as new subpopulations), (3) for new dosages or durations, or (4) as the basis for approving a related drug or device (such as a generic or biosimilar drug). Although the logic of preapproval testing and the precautionary principle-first, do no harm-would counsel in favor of prohibiting extrapolation approvals until after traditional safety and efficacy evidence exists, such delays would unreasonably sacrifice beneficial uses. The harm of accessing unsafe products must be balanced against the harm of restricting access to effective products. In fact, the Food and Drug Administration's (FDA's) current regulations in many ways reject the precautionary principle because they largely permit individual physicians to prescribe medications for off-label uses before any testing tailored to those uses has been done. The FDA 's approach empowers physicians, but overshoots the mark by allowing enduring use of drugs and devices with insubstantial support of safety and efficacy. This Article instead proposes a more dynamic and evolving evidence-based regime that charts a course between the Scylla and Charybdis of the overly conservative precautionary principle on one hand, and the overly liberal FDA regime on the other.