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As children are experiencing the highest rates of COVID-19 in many states, can efforts to universally preclude vaccination of those under 12 until the U.S. Food and Drug Administration (FDA) specifically authorizes use in that age group be justified?
In a case commentary published today in Pediatrics, we argue that the answer is no.
This view diverges from the positions of the American Association of Pediatrics, FDA, and the U.S. Centers for Disease Control and Prevention (CDC). In fact, the CDC, which controls the nation’s supply of COVID-19 vaccines, has taken steps to currently ban the practice of vaccinating youth under the age of 12.
We acknowledge that recommendations to widely vaccinate 5-11 year olds should await FDA and CDC guidance (which is expected soon, given upcoming advisory committee meetings). But, especially at the lower dose offered in pediatric clinical trials, we think that off-label pediatric administration of approved COVID-19 vaccines, like Pfizer’s Comirnaty mRNA vaccine, should be treated like other off-label uses and left to the individual risk-benefit judgments of doctors and patients (or here, parents).
Off-label use refers to providing an approved (not merely authorized) product at a different dose or to a different population than that for which it was approved. As of today, providing Comirnaty to children under 12 at any dose would be an off-label use, as would certain “booster” uses, such as providing the Pfizer vaccine to previous recipients of the Johnson & Johnson one-dose vaccine. Off-label uses often lack the same evidentiary support as approved uses and should therefore be treated with caution.
But off-label uses are generally legal and very common in pediatrics. While less common for vaccines, CDC has previously recommended the off-label use of pediatric vaccines in specific contexts — for instance, for infants traveling to countries with high Hepatitis A risk.
Moreover, even though FDA review of trial data is critical, waiting for authorization of an off-label use of an approved product may have particularly high costs in a pandemic for children with conditions that substantially raise their risk of COVID-19 complications. This has prompted other countries to permit case-by-case access to Comirnaty for high-risk children under 12. Additionally, Pfizer has released summary results from pediatric clinical trials that seemingly support the safety and effectiveness of their vaccine in children 5-11.
Rather than leaving off-label COVID-19 vaccination to the usual discretion of clinicians, there have been various efforts to prevent it. For example, the CDC has warned that vaccine provision off-label “may not” be eligible for compensation for vaccine injury under the Countermeasures Injury Compensation Program (CICP), or for the liability protections provided by the Public Readiness and Emergency Preparedness (PREP) Act. We disagree and believe it would most likely be eligible for both, given that off-label use does not negate the presence of a covered person or covered countermeasure under the law.
The most compelling legal basis for limiting vaccine access for children under 12 is CDC’s own agreements with vaccine providers, which require them to administer COVID-19 vaccines in accordance with CDC guidance or risk expulsion from the program. Whether CDC would actually take action against off-label administration is unclear. San Francisco has been providing booster doses to Johnson & Johnson vaccine recipients for months without enforcement, even prior to full Comirnaty approval. But federal authorities did prosecute a pharmacy in Puerto Rico for vaccinating children under 12 and submitting claims to Medicaid for those vaccinations. Those vaccines, however, were only under emergency use authorization (EUA), making their use unauthorized, rather than off-label.
We think the CDC should consider loosening the language in its Provider Agreements and clarify its interpretation of the CICP and PREP Act to make clear that compensation and liability protections continue despite off-label use. Enabling physicians to use their clinical judgment in offering COVID-19 vaccines off-label at the pediatric trial dose to children deemed to be at heightened risk would likely reduce harm, both by reducing COVID-19 cases and hospitalizations in unvaccinated children and by decreasing the role of deception and dosing guesswork in vaccine provision.
We have more to say in our Pediatrics essay. Although FDA is expected to authorize Comirnaty for use in children ages 5-11 in the coming weeks, the off-label question will remain relevant until all age groups are eligible for vaccination.
Patricia J. Zettler is an associate professor of law at The Ohio State University Moritz College of Law.