Off-label use: Patient, surgeon & industry

Abstract

Surgeons, by nature, are inquisitive, forward-thinking, and creative individuals. When presented with a difficult clinical problem, we call upon our previous experiences to find a rational, patient-centric, and fiscally responsible solution. The core of clinical problem solving revolves around drawing off of our collective experiences with treating similar pathology. Afterall, no two patient's pathologies are exactly the same, and as such the cares performed will vary. Furthermore, through our astute observation of cause and effect, it is only natural that we would find it completely rational to develop a “chimera” treatment plan including some concepts used for one pathology that seem, at face value, applicable to another. When we fail or, more commonly, when we are successful, we share the results with our colleagues. The natural venue for surgeons to share their innovative idea, creative adaptation of a surgical procedure, or novel application of technology is through peer-reviewed publication. Afterall, this would help validate their treatment plan, since through publication it would have withstood the rigors of scientific review. What does this have to do with Foot & Ankle Surgery: Techniques, Reports & Cases (FASTRAC)? Well, I have witnessed an influx of submissions that involve patients receiving care with “off-label use.” As defined by the United States Food & Drug Administration (US FDA), off-label use is, “…prescribing medications for indications, or using a dosage or dosage form, that have not been approved by the US FDA”.1Understanding unapproved use of approved drugs "off label". Available at:https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label . Accessed July 18, 2021Google Scholar Interestingly, much of what we do as foot & ankle surgeons involves off-label drug or product use.2Wittich C.M. Burke C.M. Lanier W.L. Ten common questions (and their answers) about off-label drug use.Mayo Clin Proc. 2012; 87: 982-990Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar For example, any of us who prescribe gabapentin for painful peripheral diabetic neuropathy … are in fact prescribing it off-label. This is despite being supported by numerous clinical trials and clinical consensus statements easily found by searching scholar.google.com for key words “gabapentin AND diabetic neuropathy AND consensus statement”. Although the US FDA off-label use policy has not been well enforced, it explicitly limits industry promotion of off-label use to drugs or products for which a supplemental new application is under way and also requires advance US FDA review of those articles to be used for promotion.3Peckham A.M. Evoy K.E. Ochs L. et al.Gabapentin for off-label use: evidence-based or cause for concern?.Subt Abuse. 2018 Sep 23; 121178221818801311https://doi.org/10.1177/1178221818801311Crossref Scopus (47) Google Scholar,4Wallach J.D. Ross J.S. Gabapentin approvals, off-label use, and lessons for post marketing evaluation efforts.JAMA. 2018; 319: 776-778Crossref PubMed Scopus (33) Google Scholar Who finds off-label drug use interesting? Attorneys are first in line.5Dresser R. Frader J. Off-label prescribing: a call for heightened professional and government oversight.J Law Med Ethics. 2009; 37: 476-486Crossref PubMed Scopus (129) Google Scholar, 6Rosoff P.M. Coleman D.L. The case for legal regulation of physicians’ off-label prescribing.Notre Dame Law Review. 2011; 86: 649-692Google Scholar, 7Comanor W.S. Needleman J. The law, economics, and medicine of off-label prescribing.Washington Law Rev. 2016; 91: 1167-1244Google Scholar In fact, more and more frequently, it is not US FDA action but litigation that raises important questions about off-label use. Does off-label use only involve drugs? Nope. Have you placed, 3.5-mm cannulated screws across the tarsal-metatarsal joints to treat an acute LisFranc dislocation? Well, this represents off-label product use according to certain manufacturers. So, now what? Well, after reviewing myriad manuscript submissions to FASTRAC, I have recognized that, to date, not one author has declared if their treatment included any off-label drug or product use. Since the manuscripts published in FASTRAC are freely available worldwide, it behooves us to make our off-label drug or product use clear to all readers. This is for the safety of prospective patients being treated, foot & ankle surgeons performing the care, and our industry partners selling the products employed. In order to facilitate this process, I have added to the FASTRAC “Guide for Authors” (https://www.elsevier.com/journals/foot-and-ankle-surgery-techniques-reports-and-cases/2667–3967/guide-for-authors) the need for the authors to specify if any portion of the care provided involved off-label drug or product use. If the patient cares provided by the authors involved off-label product use, then the authors will need to provide a weblink to the drug's or product's approved use(s), as well as, provide insight as to why other on-label products could not be used. This is in addition to confirming the patient received appropriate informed consent that they were receiving care involving off-label drug or product use. One benefit for our industry partners is that they can better understand how their products are being employed by foot & ankle surgeons. Over time, armed with this information, they may decide to pursue “on-label” indications for the off-label products being used or instead better educate foot & ankle surgeons on the approved indications and contraindications for the products in question. Finally, the foot & ankle surgeons reading FASTRAC will be able to determine if the approach taken by the authors warrants the potential medical-legal risks associated with off-label drug or product use in their own practices. Be well, Tom The author declared no potential conflicts of interest with respect to research, authorship, and/or publication of this article.