Understanding COVID-19 Vaccine Trials in Children
Jul 13, 2021 Amy Paturel
Clinical trials to test the safety and efficacy of COVID-19 vaccines in children under 12 are officially underway (The COVID-19 vaccine made by Pfizer-BioNTech is already authorized for emergency use in anyone 12 and older in the U.S., Canada and the European Union. They receive the same dose as adults: 30 micrograms). Both Pfizer and Moderna are seeking to answer questions about how safe and effective their COVID-19 vaccine is in children.
"Trials for children require special ethical and clinical considerations and have to meet a higher standard before they can start recruiting participants."
In fact, as the weeks pass from summer into fall, the testing threshold will get increasingly younger. While children may not be super-spreaders of SARS-CoV-2, the virus that causes COVID-19, they are critical to achieving herd immunity. Pfizer expects to apply to the Food and Drug Administration for Emergency Use Authorization (EUA) in children as young as 2 by September. The company has already received EUA for kids ages 12 to 15.
"COVID-19 rates are now highest among children," says Dr. Priya Soni, a pediatric infectious diseases expert at Cedars-Sinai. "In fact, children make up about one-quarter of new COVID-19 cases, and despite early news reports, children can get very sick from COVID-19."
In rare cases, even kids with a mild case of COVID-19 can later develop a potentially deadly condition called multi-system inflammatory syndrome in children, or MIS-C, that can affect multiple organ systems.
But children aren't the same as adults. Scientists can't simply take an adult vaccine and begin delivering it in smaller doses. Instead, they have to develop testing protocols that account for developmental and physiological differences that are unique to children.
"Their bodies work differently, and they undergo changes as they grow from infancy toward adolescence and adulthood," says Dr. Moshe Arditi, academic director of the Division of Pediatric Infectious Diseases Allergy and Immunology at Cedars-Sinai.
Under the EUA, children between the ages of 12 to 15 receive the same dose as adults for Pfizer (30 micrograms). For younger children, early trials aimed to establish the optimal vaccine dose by dividing volunteer participants into three groups: ages 5 to 11, 2 to 5, and 6 months to 2 years. Children between the ages of 5 and 11 years in the Pfizer trial will receive 10 micrograms, but children under age 5 will only receive 3 micrograms.
Testing Vaccines in Children
Children have distinct developmental and physiological differences that affect not only their susceptibility to disease, but also how their immune systems respond to health interventions. Clinical trials designed for children—and tested in children—are the only way to develop age-specific, scientifically tested vaccines and treatments for this unique population.
"Trials for children require special ethical and clinical considerations and have to meet a higher standard before they can start recruiting participants," Dr. Arditi says.
Yet, clinical research is critical to develop safe and effective treatments and vaccines for this vulnerable population. To address these unique needs, clinical trials in children differ from those in adults in the following ways:
- Informed consent: Before anyone can enroll in a clinical trial, they need to demonstrate that they understand the risks and benefits of participating by signing an informed consent. Because children may not grasp the scope of the trial, parents have to provide consent for them. "With pediatric trials, it's a two-tiered process where both parents and children, depending on their age and maturity, agree to participate in the study," explains Dr. Soni.
- Children's trials come last: These trials happen only after a vaccine is deemed safe and effective in the lab, then in animals and finally in adults, says Dr. Fataneh Majlessipour, a pediatric oncologist at Cedars-Sinai. By the time researchers begin vaccine trials in children, we know it is both safe and effective in adults—and it has been reviewed and approved by different regulatory agencies.
- It's a stepwise process: As children grow and change, their immune systems do, too. A 6-year-old is not the same as a 16-year-old. To account for these differences, researchers do "age de-escalation" studies with participants placed in different groups. For example, 6-to-12-year-olds, 2-to-6-year-olds and 6-month-to-2-year-olds. Doses start at the lowest safest level and researchers increase them in different groups to determine whether a larger dose is more effective or whether a lower dose provides a complete response. "It's a bit like the Goldilocks effect," Dr. Arditi says.
Investigators who are testing vaccines or treatments in children must also factor in issues specific to early childhood, such as bone growth, neurodevelopmental changes, hormonal shifts, social and emotional development and other concerns.
"With the COVID-19 vaccine, for example, we need to make sure it doesn't interfere with immunity generated by routine childhood vaccinations—and that standard vaccination protocols are not interfering with the COVID-19 vaccine," Dr. Arditi says. "And that's going to take some time to assess."
The Perks of Participation
Clinical trials allow kids to play a key role in advancing scientific knowledge. Your child's participation could result in scientists uncovering more effective vaccines—or achieving herd immunity for a deadly virus.
"Children who are in clinical trials tend to be very well connected with their providers," Dr. Soni explains. "They often receive closer monitoring and additional testing that wouldn't be accessible otherwise. So, not only are these children helping to advance science, but they're also getting specialized care and a concierge sort of attention."