How the vaccine will be studied in kids
The pediatric vaccine trials will not be as large as the final stage adult trials, which enrolled 30,000 or more participants, giving a placebo to half and the vaccine to half. Pfizer’s 12- to 15-year-old study has enrolled 2,259 participants and Moderna’s adolescent trial is a similar size, aiming for about 3,000 participants. In both trials, some teens will receive a placebo.
That’s enough to prove safety and benefit, experts said, in part, because the adult trials have already paved the way. To show the vaccine is safe, among the many things that Pfizer is tracking includes the percentage of participants reporting “local” reactions such as pain at the injection site, redness and swelling, as well as the percentage of participants reporting systemic reactions such as fever, headache, chills, vomiting, diarrhea, muscle pain and joint pain.
After the trials are completed, tracking for any safety issues will continue in the real world as physicians and patients will be encouraged to report to the FDA and CDC any side effects they think may be due to the vaccine.
Doctors said they’d want to make sure that there are no signs that the vaccine overinflames the immune system or causes any allergic or autoimmune responses. “I think most people that are developing these vaccines feel like the vaccine is not going to trigger MIS-C, but it’s something that will be monitored for very closely both in the trials and more importantly, post-licensure,” added O’Leary, from the University of Colorado. Maldonado said she’ll also be on the lookout for any cases of Guillain-Barré syndrome, which is often a concern when it comes to vaccines, but she noted that no significant increases in cases were seen in any of the adult trials.
When it comes to proving benefit, the pediatric trials will focus on a different metric than the adult trials. The adult trials’ primary efficacy measure was to compare how many vaccinated people wound up sick with COVID-19 symptoms compared with those who received the placebo and whether the vaccine impacted the severity of illness. Since children rarely are hospitalized due to COVID-19, the vaccine’s ability to reduce severe cases would be hard to measure unless the trials enrolled an enormous number of children.
Instead, Pfizer’s and Moderna’s adolescent trials will focus on evaluating participants’ immune response by measuring antibodies, according to Pfizer’s spokeswoman and Moderna’s clinical trial website.
Scientists haven’t yet identified an “immune correlate of protection,” which is usually defined to be the level of antibodies in the blood at which they can feel confident that a person is going to be protected from infection. Some vaccines that have been approved, like the one for measles, have an immune correlate of protection identified, while others don’t.
In the absence of a definitive immune correlate of protection, the trials would compare antibody levels in children with those found in adults and extrapolate that the efficacy should then be similar. The FDA and advisory groups like the CDC’s Advisory Committee on Immunization Practices would then need to discuss whether the evidence is compelling. If scientists are able to identify an immune correlate of protection, however, “and you can demonstrate that kids get that with the vaccine, that’s even more satisfying,” O’Leary said.
One final difference in pediatric studies is the potential for lower doses. Moderna has said that it will run its studies of children under 12 testing lower doses first.
“As we go down in age, we give the smallest possible dose of vaccine that we think is reasonable, and then we steadily increase until that point when we get that magic ‘Goldilocks’ level at which it works great and the side effects are tolerable,” Vanderbilt’s Creech explained. “I don’t think one dose fits all.”