Vaccine makers are asked to expand safety studies on children

By Sheryl Gay Stolberg, Sharon LaFraniere and Noah Weiland

At the urging of federal regulators, two coronavirus vaccine-makers are expanding the size of their studies in children ages 5 to 11 — a precautionary measure intended to detect rare side effects including heart inflammation problems that turned up in vaccinated people under age 30.

Appearing at a televised town hall-style meeting in Ohio last week, President Joe Biden said that emergency clearance for pediatric vaccines would come “soon.” The White House has declined to be more specific on the timeline, and it was unclear how much of an effect, if any, expanding the studies would have on when vaccines could be authorized for young children.

Multiple people familiar with the trials said the Food and Drug Administration had indicated to the two vaccine-makers, Pfizer-BioNTech and Moderna, that the size and the scope of their pediatric studies, as initially envisioned, were inadequate to detect the rare side effects. Those include myocarditis, an inflammation of the heart muscle, and pericarditis, inflammation of the lining around the heart.

Questions about vaccinating children — including those under 12 — are of huge interest to parents and teachers. Regulators will be required to balance potential side effects of coronavirus vaccination against the risks of COVID-19.

Members of a Centers for Disease Control and Prevention advisory committee have said that the benefits of shots for people older than 12 greatly outweigh the risks, including of heart problems. Children 12 and older have been eligible for the Pfizer shot for months even as studies continue on the safety of the Pfizer and Moderna vaccines for younger children.

The FDA has asked the companies to include 3,000 children in the 5- to 11-year-old age group, the group of younger children for which results were expected first, according to people familiar with the situation. That is double the original number of study participants envisioned in the Pfizer trial for that age group, two people said. The study initially sought to enroll 4,500 patients under 12, split into a group of 5- to 11-year-olds and two younger age groups, according to a government website.

A spokesperson for Moderna, Ray Jordan, confirmed that the company intended to expand its trial “to enroll a larger safety database, which increases the likelihood of detecting rarer events,” and expected to seek emergency authorization in “winter 2021/early 2022.”

The Moderna trial began recruiting patients in March with the aim of enrolling 6,795 participants under 12, also split equally into three age groups, including a group of 6- to 11-year-olds. Jordan said the company was “actively discussing” a proposal with the FDA to expand the study.

Pfizer is on a faster timetable than Moderna, and may be able to meet the FDA’s expectations on a bigger trial size and still file a request to expand emergency authorization of its vaccine by the end of September. Reviewing all the safety and efficacy data will most likely take regulators at least a few weeks.

Pfizer has previously said it expects to have results for the 5- to 11-year-old group in September, with results for children ages 2-5 shortly after. Results for the youngest children, between 6 months and 2 years old, are expected in October or November. A spokesperson said Monday that the company had no updates on its timetable.

A spokesperson for the FDA, Stephanie Caccomo, declined to offer specifics. “While we cannot comment on individual interactions with sponsors, we do generally work with sponsors to ensure the number of participants in clinical trials are of adequate size to detect safety signals,” she said in an email.

In June, the CDC published data showing that the two vaccines may have caused myocarditis and pericarditis in more than 1,200 Americans, including about 500 who were under age 30. The symptoms typically appeared within two weeks and were more common in young men and boys. The rate was low: fewer than 13 cases per 1 million second doses administered.

Most cases were mild and quickly cleared up, the researchers said. And Dr. Paul A. Offit, an infectious disease specialist who previously served on the CDC’s Advisory Committee on Immunization Practices, which makes recommendations on vaccine use in the United States, noted that infection with the coronavirus also carried a risk.

If expanding the trials were to cause a delay in authorizing vaccines for pediatric use, he said, that would also put children at risk. “There’s always a human price to pay for knowledge,” he said. Of the heart ailments, he said: “It’s rare. It’s generally short lived and self resolving. It’s also a consequence of natural infection.”

The CDC’s data showed 12.6 cases per 1 million second doses administered, and researchers estimated that out of 1 million second doses given to boys ages 12-17, the vaccines might cause a maximum of 70 myocarditis cases, but would prevent 5,700 virus infections, 215 hospitalizations and two deaths. COVID-19 itself may cause heart problems in young people.

The FDA authorized the Pfizer vaccine on an emergency basis for children ages 12-15 in April; so far, the Moderna vaccine has been cleared only for people 18 and older. The agency attached a warning about potential heart problems to the fact sheets of the vaccines in June.

Many public health experts argue that with so much attention focused on hospitalizations and deaths among older Americans infected with the coronavirus, the risk for children has been overlooked. The American Academy of Pediatrics reported last week that more than 4 million American young children and adolescents had tested positive for the virus and 349 had died since the outset of the pandemic.

Biden’s attempt to put a general timeline on a possible authorization for children younger than 12 was unusual, and risked setting expectations for regulators to resolve a highly sensitive matter too soon. Biden and members of his administration have said they do not want to intervene in or be seen as influencing the work of regulators at the FDA — something that former President Donald Trump tried to do repeatedly last year as the agency reviewed coronavirus drugs and vaccines.

Government regulators and scientists have been hamstrung in recent months by a patchwork of sometimes weak data collection systems in the United States for vaccine side effects, forcing them to lean on a program called the Vaccine Adverse Event Reporting System, a 30-year-old federal monitoring system that relies on self-reported cases from patients and health care providers. That dilemma has increased the pressure on companies to do more rigorous studies in children.

“There is a clear and well-defined risk to delaying the availability of these vaccines” in young children, said Dr. Steven Black, an emeritus professor of pediatrics at Cincinnati Children’s Hospital Medical Center and the co-director of the Global Vaccine Data Network, a consortium that researches the safety of vaccines.

Black said that because of how rare the conditions were, increasing the size of the studies might not allow regulators to better detect the prevalence of the heart problems.

“The only way we’ll know about that is to roll the vaccine out and see what happens,” he said. “Passive reporting will probably be very good because I think we’re sensitized to the issue. We know to look for it. Physicians know to look for it.”

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