Bioethics Forum Essay

With Pediatric Hospitalizations Rising, Reconsider Off-Label Covid Vaccination for Young Children

Pfizer recently announced that its trials in children 2 to 5 years old produced a weaker than expected antibody response and that it would hold off requesting authorization from the Food and Drug Administration. It was a clinical disappointment, and also an emotional blow to families (including some of our own) with a child under 5 who will be waiting longer to be vaccinated. Pfizer is testing a three-dose-series in these youngest kids, with results (and hopefully authorization) anticipated in the first half, as opposed to the first months, of the year.

The news from the Pfizer trial creates opportunities – and additional challenges – for off-label use of Covid-19 vaccines in children, which we’ve previously argued should be both ethical and legal. Although off-label vaccination is not a strategy for widespread vaccine access, it ought to be an option for some individual children when the potential benefit of immediate vaccination could outweigh the risks. The news from Pfizer does not change our analysis, but it does provide more information about anticipated risks and benefits.

According to our research, the Centers for Disease Control and Prevention’s prohibition against pediatric off-label use of Covid-19 vaccines in its vaccine provider agreement was ethically and legally unprecedented.  For children under 5 with high-risk medical conditions in particular, pediatricians and parents should be able to make the decision to vaccinate off-label together, as is possible to do for any other off-label use of medications or vaccinations.

To be clear, using vaccines off-label has both risks of unknown or rare side-effects, and logistical obstacles — even if the CDC Covid-19 vaccine provider agreement didn’t stand in the way. The update from the under 5-year-old Pfizer trials further illustrates these challenges. But paired with record pediatric hospitalizations, the news also underscores potential benefits of access to off-label vaccination.

Off-label means using an FDA-approved product for a different indication or population, or at a different dose, than that for which it was approved. The FDA fully approved the Pfizer-BioNTech Covid-19 vaccine as a two-dose series of 30 micrograms each for people ages 16 and older in August. The vaccine for children ages 12 to 15 uses the same dosage but is only authorized for emergency use.

In kids ages 5 to 11, a lower 10 microgram 2-dose series of the same formulation, administered with smaller needles, is FDA-authorized for emergency use. Because the Covid-19 vaccine for 5- to-11-year-olds is not fully approved, pediatricians can’t use it off-label to vaccinate younger kids. But they could modify the dosing of the fully approved version.

In the American Academy of Pediatrics statement against off-label vaccination, Dr. Yvonne Maldonado said, “We do not want individual physicians to be calculating doses and dosing schedules one-by-one for younger children.”

If pediatricians were to engage in off-label vaccination, they would have to determine an appropriate dose. One option could be to follow the ongoing clinical trials using 3 micrograms of vaccine in children under 5. Other options involve relying on clinical judgment and available data to determine an alternate dose. This is what the AAP was trying to avoid. Administering alternate doses outside of clinical trials does not involve the close monitoring and reporting that comes with doing so inside a clinical trial.

For this reason, engaging in variable dosing regimens prior to vaccine authorization might ideally be done in “open-label” trials. However, these trials involve additional time and resources to initiate and may not be accessible to the individuals for whom potential benefits of off-label vaccination might still outweigh risks.

The results of the 2-to-5-year-olds trial suggest that anticipated benefits of off-label vaccination may not be as significant as intended. But they also show that the known risks remain low. According to Pfizer, the trial dosing showed “no safety concerns” and “demonstrated a favorable safety profile in children 6 months to under 5 years of age.” Two reports from the CDC confirmed minimal adverse events in young children who have been vaccinated against Covid-19.

Extending the timeline for completion of clinical trials for children under 5 also extends the risks of remaining unvaccinated –  especially as a new variant circulates and Covid-19 cases continue to climb in kids. CDC projections indicate the Omicron variant will create a peak of infections in the U.S. in January that could extend to April. Current estimates suggest that a vaccine will not be authorized for children under 5 before the spring.

While children are more likely to have mild cases of Covid-19, some do experience severe illness or death. Pediatric hospitalizations have as much as quadrupled in some parts of the country, primarily among unvaccinated children – many without the option to become vaccinated. New York State, for example, reported at the end of December that approximately half of pediatric hospitalizations with Covid-19 are among children under 5. As of early January this trend continues, with CDC data indicating that the “steep rise” in children hospitalized with Covid-19 infections nationwide is among children under 4.

Off-label vaccinations could protect individual children at greatest risk of severe Covid-19 infection this winter and spring. One of the greatest risks of off-label vaccination at the trial dosing is that it might not be as effective as hoped. But for families of high-risk kids and their doctors, this might be a risk they would like to be able to take.

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.