Timing, Ethics Factor Into COVID-19-Vaccine Trial Enrollment Of Minors

As manufacturers of COVID-19 vaccines consider when and how to enroll minors into clinical trials, several factors such as timing and ethics should be considered, according to a team of pediatricians and bioethics specialists.

Starting too soon can expose minors to research risks, but waiting too long could prolong the pandemic and hold back vital vaccines for children and their families, the team writes in Pediatrics.

"In standard cases, trials don't enroll minors until found to be safe and efficacious in adults, but in the case of COVID-19 vaccines, that could delay an effective response to the pandemic by six months to two years," said senior author Dr. David Wendler of the National Institute of Health's Department of Bioethics in Bethesda, Maryland.

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"Our view is that vaccine trials tend to be much larger and can show safety data," he told Reuters Health by phone. "We have so much safety data that it could be justifiable to enroll kids."

Dr. Wendler and colleagues proposed recommendations for when and how to enroll minors in COVID-19-vaccine trials based on several factors. Although most infected children develop no or only mild symptoms, they write, those from racial and ethnic minority groups and those who have disabilities or underlying health conditions can experience severe illness and develop a multi-system inflammatory syndrome in children (MIS-C).

More than 1,000 children have developed the syndrome in the U.S., and more than 250 children have died from COVID-19, which is higher than the 188 minors who died during the most recent flu season.

The pandemic has also created significant social and personal harm for minors due to the closure of schools, daycare centers and extracurricular activities, the authors write. School-aged children haven't received the educational and social benefits of in-person interactions, as well as the food, safety and care that schools and programs offer many children. Overall, a safe and effective vaccine would benefit minors, their families and society, they write.

"With careful planning, it's possible for research to enroll minors in a way that is ethical and can speed the process to find a vaccine to end the pandemic," Dr. Wendler said.

Importantly, Dr. Wendler and colleagues write, minors can't provide informed consent, so it's advisable to enroll children after clinical trials show sufficient safety and efficacy data in adults.

With the current COVID-19-vaccine trials, the approach could be to enroll minors after sufficient safety data in adults but before the evidence of efficacy, which should start with children who are most similar to the adults enrolled in the trials. Researchers should pay attention to the groups that were included or excluded in the adult trials and first enroll older adolescents who are similar to adults physiologically.

To further minimize risks, enrollment should begin with a small number of older, healthy adolescents, the authors suggest. If no safety concerns are identified, trials can proceed with a larger group of older adolescents and then include younger minors.

The most challenging group, ethically, is younger children who may not understand the clinical trial and minors with health conditions that put them at an increased risk for COVID-19 complications. These groups shouldn't be enrolled until enough safety data exists.

When beginning clinical trials in children, vaccine companies and sponsors should also form community partnerships to ensure that participants reflect the geographic and demographic diversity of those affected by the pandemic, the authors write.

Partnerships can bolster recruitment, address community concerns and create a fair selection process when there are more interested participants than slots available. Community groups may also help build public trust in the research process, which makes it more likely that both children and adults will take a vaccine when one is available.

"Children are really suffering during the COVID-19 pandemic," said Dr. Ed Anderson of Emory University School of Medicine in Atlanta, Georgia. Dr. Anderson, who wasn't involved with this paper, has written about the benefits of enrolling children in COVID-19-vaccine trials.

"We ought to ensure that we do all that we can do to advance vaccine options for them quickly and safely," he told Reuters Health by email.

—Carolyn Crist

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