In a new essay in the Hastings Center Report, we argue it is not. Yet the practice is prohibited under the Centers for Disease Control and Prevention’s Covid-19 vaccine provider agreement, and the American Academy of Pediatrics (AAP) supports the prohibition. Our research suggests that although off-label vaccination is not a public health solution to increasing access to Covid-19 vaccines for all kids, it should be an ethically and legally permissible solution available to at least some kids, especially those at high risk of complications from Covid-19.
Off-label use refers to the administration of a medicine for a population or an indication for which it was not approved. As the public takes an interest in and pays close attention to Covid-19 vaccine authorizations and approvals, many people are learning about off-label use for the first time, and it may sound alarming, experimental, or rare. However, off-label use is incredibly common.
Studies suggest that 10% to 20% of routine prescriptions are off-label, and off-label prescribing is even more common in pediatrics. For example, a retrospective study found that patients in 28% of pediatric visits received at least one off-label prescription and more than 50% of pediatric hospitalizations involve at least one off-label medication. The AAP endorses off-label use as a necessary tool “to benefit an individual patient” and recognizes its importance in pediatrics since fewer clinical trials are conducted in children, resulting in fewer products FDA-approved specifically for children.
However, in a statement issued the same day that the Pfizer-BioNTech Covid-19 vaccine received FDA approval for people ages 16 and older, the AAP cautioned “against off-label use of Covid-19 vaccines in children under 12.” The AAP’s primary reason was dosing differences between the approved adult formulation and the trial doses in kids under 12. (Clinical trials in kids ages 5 to 11 and under 5 each use lower doses than the 30 micrograms authorized for ages 12 to 15 and approved for ages 16 and up). Though off-label use permits, and often requires, dosing different than what the FDA approved, there are risks in relying on dosing guidance from incomplete clinical trials.
But the risks of determining and administering appropriate doses before trials are complete may not outweigh anticipated benefits of vaccine access in all cases. This is especially true for kids at increased risk of severe Covid-19 due to underlying health conditions, as described in a recent article in Pediatrics, or because they live and go to school in settings with low vaccination rates or that do not enforce, or allow, evidence-based mitigation strategies like masking to reduce viral spread.
Our research suggests that while off-label use of pediatric Covid-19 vaccines should be ethically permissible, in line with norms for other off-label uses, there are unique legal barriers that stand in the way. The CDC’s Covid-19 vaccine provider agreement indicates that when using “federally purchased Covid-19 vaccines” the “age of the vaccine recipient must align with . . . FDA Emergency Use Authorization or Approval of the administered vaccine.” The CDC also implies that providers who don’t follow this agreement risk liabilities that typically do not apply to off-label use.
The CDC and AAP guidance portray off-label use of Covid-19 vaccines as contrary to standard practice, and as ushering in a host of negative repercussions. However, our analysis suggests that it isn’t off-label use of Covid-19 vaccines that departs from clinical, ethical, or legal norms. It is the strict prohibition of off-label use that is the exception.
The FDA recently authorized the Pfizer-BioNTech Covid-19 vaccine for 5-to-11-year-olds, and this is good news. But for a time during the FDA’s Vaccines and Related Biological Products Advisory Committee meeting to discuss and vote on authorization, it was unclear what the outcome would be. Committee members emphasized that highest-risk kids should have access to a vaccine and even considered limiting authorization to this group. Ultimately, to get high-risk kids access and to support broader vaccine equity, the VRBPAC recommended authorization. But if off-label use of Covid-19 vaccines had been on the table, then children at high risk could already have had Covid-19 vaccine access. The decision for individual children would have depended on whether their parents and pediatricians believed an off-label Covid vaccine was appropriate for them.
After a high number of Covid-19-related pediatric hospitalizations in August and September, they are now fortunately on the decline, and pediatric deaths remain low. But as AAP President Lee Savio Beers recently wrote in the New York Times, “there is simply not an acceptable number of child deaths when such effective and safe preventative treatments are available.” For high-risk kids under 5, for whom no vaccine is yet authorized, off-label use of the fully approved Pfizer-BioNTech Covid-19 vaccine is an ethically permissible option, if only the CDC vaccine provider agreement did not stand in its way.
Elizabeth Lanphier, PhD, MS (@EthicsElizabeth), is an assistant professor in the Ethics Center at Cincinnati Children’s Hospital Medical Center and in the departments of pediatrics and philosophy at the University of Cincinnati, as well as a nonresident research fellow in the Institute for Philosophy and Public Policy. Shannon Fyfe, PhD, JD (@sefyfe), is an assistant professor of philosophy at George Mason University, where she is also a fellow in the Institute for Philosophy and Public Policy and an adjunct professor at the Antonin Scalia Law School.
November 09, 2021