Covid-19 vaccines for kids: FDA spells out questions on immunobridging, safety followup ahead of adcomm
NIAID chief Anthony Fauci predicted days ago that Covid-19 vaccines for younger children will be available by the end of the year or early next year. But what requirements should they satisfy before getting the clearance from the FDA? The agency laid out some of its thoughts on briefing documents for an advisory committee set for Thursday.
As with the first expert panels convened to discuss Covid-19 vaccine regulations, the adcomm won’t be talking about specific products. Rather, the goal is to gauge their opinion on framework, such as data needed and appropriate endpoints.
Right now, Pfizer and BioNTech have the only shot that’s authorized for adolescents above the age of 12 — but nothing is sanctioned yet for those younger. (Canada and the EU, though, have greenlighted Moderna’s jab for the same population.)
Regulators set the stage by noting that although pediatric populations seem less likely to be infected by the coronavirus (and when they do, tend not to get as sick), many have still been hospitalized or died from Covid-19:
As of May 25, 2021, approximately 553,000 and 2.7 million COVID-19 cases, respectively, were reported in children 0-4 and 5-17 years of age in the US, among which 121 (0.02%) and 278 (0.01%), respectively, were fatal, and more than 38,000 of which resulted in hospitalizations reported since August 1, 2020, in patients 0-17 years of age
The FDA emphasized that any authorization for pediatric use should follow “substantial evidence of effectiveness from adequate and well-controlled trials” plus ample safety data. Yet with three vaccines from Pfizer/BioNTech, Moderna and J&J already showing efficacy in adults, they wonder if the evidence could take a different shape.
Given the lower infection, hospitalization and death rates in children, after all, the dynamics are quite different.
FDA acknowledges that direct demonstration of effectiveness in field efficacy trials may not be feasible in pediatric populations and thus, following direct demonstration of protection in adults, effectiveness of the same vaccine could be inferred in pediatric populations by immunobridging. … In this approach, an immune response biomarker(s) elicited by the vaccine in a pediatric age group is compared to the same immune response biomarker(s) elicited by the same vaccine in a relevant adult age group, with formal statistical hypothesis testing to demonstrate that the measured immune response in the pediatric age group is non-inferior to that in adults.
There are also questions about whether there should be a longer safety followup than the two months mandated for the adult and adolescent OKs.
One other specific consideration for children, the FDA added, would be how the Covid-19 vaccine might interfere with other routinely recommended immunizations. Vaccine makers are encouraged to include information but will not be required to assess concomitant administration to support licensure.