Off-label prescribing is an integral part of contemporary medicine. Many patients benefit when they receive drugs or devices under circumstances not specified on the label approved by the Food and Drug Administration. An off-label use may provide the best available intervention for a patient, as well as the standard of care for a particular health problem. In oncology, pediatrics, geriatrics, obstetrics, and other practice areas, patient care could not proceed without off-label prescribing. When scientific and medical evidence justify off-label uses, (...) physicians promote patients’ interests by prescribing products off label.Off-label prescribing can also harm patients, however. The potential for harm is greatest when an offlabel use lacks a solid evidentiary basis. A 2006 study examining prescribing practices for 169 commonly prescribed drugs found high rates of off-label use with little or no scientific support. Researchers examining off-label use in U.S. children’s hospitals concluded, “[W]e still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”. (shrink)

How should one think about innovation in medicine and surgery? Increasingly, the answer to this question has involved reference to what might be called the regulatory ethics paradigm (REP). The regulatory ethics paradigm holds that deviations from standard care involve a degree or kind of experimentation that requires the application of a set of procedures designed to assure the protection of the rights and welfare of the subjects of research. In REP, innovative treatments are regarded as questionable until they are (...) framed in a research protocol with formal mechanisms of informed consent. The protocol must be reviewed and approved by an Institutional Review Board (IRB) or equivalent. The regulatory ethics paradigm in effect imposes the condition that clinical innovations be conducted according to scientific research methodologies. It creates the presumption that without review by an IRB, innovation cannot be conducted in an ethically defensible fashion. The regulatory ethics paradigm also requires the preparation of investigational protocols according to sound evidentiary and methodological standards. In so doing, it creates a presumption that innovations that are not rigorously validated are ethically dubious. These assumptions have deep roots. The Belmont Report, for example, articulated the orienting intuition that “radically new procedures... should... be made the object of formal research at an early stage [emphasis added] in order to determine whether they are safe and effective”.1 The Belmont Report takes the view that formal research to establish safety and efficacy of new interventions is usually feasible at an early stage in the development of a novel intervention. It thus establishes a bias that innovative treatments be conducted and evaluated under a research protocol that has passed muster at an IRB review. Given the …. (shrink)