Baby held in someone's arms.

Remember the Babies: The Need for Off-Label Pediatric Use of COVID-19 Vaccines

By Carmel Shachar

As trials stall and the omicron variant surges, the U.S. Centers for Disease Control and Prevention (CDC) is failing parents by preventing off-label use of our existing COVID-19 vaccines in the under-five set.

The cries of frustration, anger, and fear from parents of small children have reached a new pitch amidst the ruckus of 2022. Parents of children under five years old need to navigate omicron-fueled rising pediatric hospitalization rates while their kids remain entirely unvaccinated. They must also juggle childcare and work responsibilities amid unpredictable, lengthy daycare and schooling closures. Give us the vaccine to help protect our kids, shorten quarantines, and keep children in care they all clamor.

But where are the vaccines for the pediatric set — the same vaccines that have been proven safe, both in adult populations and in older children? So far the story has focused on disappointing efficacy results and delays in studies from Pfizer and Moderna. But that is not the entire explanation for why parents of small children are blocked from vaccinating their offspring.

The CDC, through its vaccine provider agreements, prevents physicians and parents from pursuing off-label use of COVID-19 vaccinations in young children. This exceptionalism is difficult to justify considering the strong safety profile of these vaccines in other age groups and the benefits of being vaccinated. It also runs counter to our approach on other cutting-edge questions regarding the implementation of COVID-19 vaccinations, such as their use in pregnant women or mix-and-match boosters.

Off-label use, or administering a U.S. Food and Drug Administration (FDA)-approved product for a different population, use or dosage than it was approved for, is very common in medicine. Research on certain populations, such as pregnant women or children, is more difficult, meaning that pharmaceutical companies are less likely to have the data to get approval for these populations to use their products. Accordingly, pharmaceuticals are often used in these populations off-label. One study found that 28% of hospital pediatric visits involved at least one off-label medication. This means if your child has needed to go to the hospital, there is a one in four chance that you’ve already allowed him or her to receive an off-label medication. This same study showed that rates of off-label use are even higher in some of the youngest children, with children 29 days to a year old receiving off-label prescriptions 44.8% of the time. Even the CDC has, at times, recommended off-label use of other vaccines in children and infants.

Unusually, physicians and patients cannot pursue off-label pediatric COVID-19 vaccinations because the CDC’s COVID-19 vaccine provider agreement requires providers to only administer this vaccine according to FDA Emergency Use Authorization (EUA) or approval. Physicians who violate this agreement could risk liability. It also means that physicians and patients seeking off-label use of COVID-19 vaccinations may not be covered under either the Countermeasures Injury Compensation Program or the National Vaccine Injury Compensation Program, which would reduce the ability of patients to be compensated for any vaccine injuries, while opening physicians to lawsuits.

The CDC could easily and quickly modify their agreement to allow off-label use, especially in the case of young children with heightened risk factors. Or Congress could direct the CDC to modify this agreement. At that point, physicians and parents could make informed decisions as to whether to administer a COVID-19 vaccine or wait until they’ve received an EUA for young children.

To be sure, there are drawbacks of allowing off-label pediatric COVID-19 vaccinations. The first is that we don’t yet know the optimal dosing for babies and young children. Before the EUA for children ages 5-11 was issued, the American Academy of Pediatrics came out against off-label use for this reason. And because the COVD-19 vaccine dosage for children ages 5-11 is under an EUA, technically we can’t just use those doses for their little brothers and sisters. But physicians could modify adult doses, likely using the amount administered for the elementary school set as a guideline. And even the AAP’s statement, drafted before omicron, acknowledged that children are in danger as trials drag on and as the adults around them fail to get vaccinated.

Another drawback of off-label pediatric use is that we will lose a lot of data informing us of the safety and efficacy of COVID-19 vaccinations in children under five. Parents will go get shots for their children, but not report outcomes anywhere. But we can recapture some of this data through registries and cohort studies. This would be a similar approach to the one we took regarding pregnant women and COVID-19 vaccines initially. Back at the start of 2021, pregnant women were told to make an informed decision with their physicians about a vaccine that had never been tested in that population. Women who went forward with vaccination were asked to enroll in registries and self-report. And scientists were able to draw meaningful conclusions regarding safety from those registries. This approach was the right choice in light of the vaccine’s safety and the illness and death that would have resulted had we waited for studies to allow pregnant women to get vaccinated. We should use that same approach with children under five.

To be clear, this proposal is not asking to require vaccination of children under five before an EUA has been granted for pediatric use. Some parents undoubtedly will want to wait until the studies have been completed and we have better data about optimal pediatric dosing. Likewise, some physicians will feel uncomfortable calculating pediatric dosing and choose not to offer off-label vaccines to their patients. But there were 580,247 pediatric COVID-19 cases last week, some resulting in hospitalizations, and all resulting in disruptions to families already stretched very thin.

Instead, this proposal seeks to restore the ability of parents, working with their providers, to choose off-label use of vaccines to address this crisis among America’s youngest. For example, parents of children who have pre-existing conditions may be more motivated to vaccinate off-label than parents of children with no heightened risk factors.

As the mother of two children under five, this proposal is not academic to me. Over the last couple years, I’ve made the difficult decision to get vaccinated while pregnant, before there was any data around outcomes. I again made the decision to get boosted while breastfeeding. If we were offered the opportunity to get our children vaccinated, even off-label, we would again make the decision to seek protection for our children and our family.

Carmel Shachar

Carmel Shachar, JD, MPH, is the Executive Director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School. She is responsible for oversight of the Center’s sponsored research portfolio, event programming, fellowships, student engagement, development, and a range of other projects and collaborations. She is Co-Lead of the Center’s Involvement with the Regulatory Foundations, Ethics, and Law Program of Harvard Catalyst | The Harvard Clinical and Translational Science Center.

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.