Liu S, Mello MM, Kesselheim AS. Prospects for Enforcing Prohibitions on Off-Label Drug Promotion after United States v. Caronia: An Analysis of Litigated Cases. J Health Polit Policy Law. 2021 Feb 22:8893571. doi: 10.1215/03616878-8893571. Epub ahead of print.

In today’s issue of Medicolegal Monday, we’ll take a break from tragic lawsuit cases in pediatric anesthesia to review an important legal aspect of our practice: off-label prescribing. As many of you know, pediatric anesthesia is one of the areas most affected by this practice. But, what actually is off-label prescribing? Is it legal? Do we put ourselves at medicolegal risk for this practice?

First, some background. When a pharmaceutical company has developed a novel medication that they wish to market for use in the U.S., they must first apply for permission to do so from the Food and Drug Administration (FDA). The process is complex, and can be confusing, but for those interested, I outlined the basic steps in an article in the October 2020 issue of Anesthesiology. The most basic requirements are for the company to demonstrate to the FDA that the drug is effective for a specific indication, and safe, when used at effective doses for that indication. This is usually accomplished by showing the FDA results from 2 separate, properly controlled trials. Once the FDA has approved the drug for sale, based on the indication set forth by the company, that indication is listed on the drug’s “label”, which most of us know as the “package insert”. By law, the company can then only market (i.e., advertise) that product for that specific indication (see Liu article for specific references to the laws). However, any licensed physician or dentist can use that drug for whatever purposes they want. When you use a drug for an indication that has not been approved by the FDA (eg, in children) it is called “off-label” use, and it is perfectly legal. Off-label prescribing is particularly common for pediatric uses, because of the underrepresentation of children in the clinical trials that led to approval.

Pediatric anesthesia is no exception. In a review published in A&A in 2012, Smith et al. demonstrated that out of 106 drugs potentially used in pediatric anesthesia or sedation, 36 (34%) were not FDA-labeled for use in any pediatric age group, and 30 (28%) were FDA-labeled for use in only specific age groups. We would like to believe that our off-label use of these drugs is justified because we know how to use them safely, and to omit them from our practice just because the FDA hasn’t approved it for that indication or population, would be worse than withholding their use. However, allowing drug companies to actively market a drug for an off-label use is an entirely different story. Historically, no one would argue that drug companies cannot be trusted to provide truthful information to clinicians. If they could, there would be no such thing as drug regulations (“If men were angels, no government would be necessary.” Federalist 51, Hamilton and Madison). As Liu et al. point out, “manufacturers have a financial incentive to oversell the benefits of their products and undersell the risks”.

This limitation on drug company marketing was the law of the land until 2012, when a Federal Appeals court in New York overturned it on grounds that it was unconstitutional (United States v. Caronia). The court reasoned that as long as the information was truthful and not misleading, the statute violated the 1st Amendment Freedom of Speech Clause.

The Liu paper cited above has analyzed the effects of that ruling on subsequent marketing and detailing by drug reps. In brief, they found that a little over half of 42 cases analyzed (both drug and device marketing) used the Caronia holding to influence their decisions against the FDA and for the drug or device companies, a scary trend indeed.

How do these new rulings that contradict those that were originally intended to protect patients influence our practice of pediatric anesthesia? It’s been years since I’ve talked with a pharmaceutical rep, since most hospitals no longer allow their presence. But we are still exposed to a barrage of ads in journals, websites, etc. on a daily basis. Plenty of research has shown that despite our belief otherwise, we are, indeed, susceptible to subconscious bias.

TRANSITIONS: Scott Markowitz, former CHOP fellow, now at Colorado Children’s will be the inaugural Vice-Chair for Professional Development and Diversity, Equity, and Inclusion in the Washington University Department of Anesthesiology…Dolores Njoku, my former pediatric intern at Rainbow Babies, previously at Johns Hopkins for her illustrious career, has been named the Division Chief of Pediatric Anesthesiology at Washington University…A double coup for Wash U! From CHOP, superstars John Fiadjoe and Jorge Galvez have taken new positions. John will be the Associate Chief of the Department of Anesthesiology, Critical Care, and Pain Medicine at Boston Children’s Hospital, and Jorge has been named Chief of Pediatric Anesthesiology at The Children’s Hospital and Medical Center in Omaha, Nebraska. Last but far from least, CHOP Uber-fellow, quadruple-boarded Andrew Renuart has accepted a position in the Department of Anesthesiology, Critical Care and Pain Medicine at Boston Children’s. With fellows like Andrew coming down the pike, our children and grandchildren are in great hands.

And on that note, as always on Mondays,

“Let’s be careful out there!”

Sgt. Phil Esterhaus, Hill Street Blues