Off-label reports of new biologics: exciting new therapy or dubious research? Examples from recombinant activated factor VII.

摘要

Medications are licensed by the US Food and Drug Administration (FDA) for specific indications detailed in the drug package insert. Labeling indicates the treatment circumstances that have been found to be safe and effective in controlled clinical trials. The use of medications outside of these circumstances is broadly referred to as "off-label" use. Off-label use can refer to the administration of doses or duration of treatment that are beyond those specified in the package insert. More commonly, off-label use refers to the use of a medication outside the context of a clinical trial for treatment of illness for which the product has not been approved by the FDA. This latter form of off-label use is at an all-time high. A report by Knight Ridder news agency found that 21% of prescriptions representing billions of dollars of pharmaceuticals were for off-label uses . A study in the United Kingdom examined more than 2000 prescriptions for 624 children and found that 46% of prescriptions were either unlicensed or off-label . There is every reason to believe that the next decade will bring an explosion of new biologics to clinical application, and so specialists will need to consider the impact of using new agents before publication of randomized clinical trials and licensed indications. This review examines challenges and concerns that arise from the publication of reports of off-label use of new biologies before their investigation with randomized clinicaltrials. Examples are drawn from recombinant activated factor VII (rFVIIa; Novoseven, Novo Nordisk, Princeton, NJ) because this promising compound is being considered for patients in intensive care. However, I emphasize that the ideas presented are general ones and are not unique to rFVIIa in any particular way.