As potential Covid-19 vaccines speed their way through development, manufacturers and U.S. regulators have largely delayed testing in children and women who are pregnant, raising the possibility that experts will lack critical safety and efficacy data in those populations when there’s a pressing need to inoculate them.
Vaccines are always tested first in healthy adults, a population that is most likely to provide a clear picture of whether a vaccine triggers protection. It’s also a population deemed to be at lowest risk should there be side effects from an experimental vaccine.
But the Covid-19 pandemic has triggered a race to vaccinate all Americans as soon as possible, beginning early next year. Even though most experts argue that children and women who are pregnant or breastfeeding won’t be at the front of the line when the first doses become available, others see a need for answers on whether the vaccines are safe and effective in these populations sooner rather than later.
“There’s going to be a huge push to vaccinate children because of schools… so we can open schools more safely,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy.
Manufacturers that are testing the vaccines in clinical trials have so far not included pregnant women or women who are breastfeeding. And only one of the vaccine makers that may end up supplying the American market, AstraZeneca, has started to test its vaccine in children.
Meanwhile, given the preponderance of women of reproductive age who work in health care or who are first responders, any plan to put workers from those sectors at the front of the vaccine line has to take into account the certainty that women who are pregnant are among them. At least some may not know it yet at the time they are vaccinated.
“I think that there’s a recognition that if we don’t have a vaccine that we can reasonably offer for safe use in pregnancy, then we’re going to have a real problem in terms of covering the populations that we know we need to cover,” said Carleigh Krubiner, a policy fellow at the Center for Global Development, a think tank in Washington.
Women who are pregnant have historically been left out of all kinds of clinical trials. Krubiner, who is part of a collaboration that has championed the need to include pregnant women in the testing of new vaccines, said this time she knows the issue is on people’s radar, but the studies haven’t yet begun.
“There is certainly a plausible scenario where we have an emergency use authorization [for a vaccine] or a licensed product where there is not any robust data on the product in pregnancy,” she told STAT.
Other populations too are traditionally slower to get invited to take part in clinical trials for vaccines, either because of perceived risks to them or because the data generated when they are vaccinated may not provide the most compelling evidence of efficacy. People who are HIV positive are an example of the former, older and elderly adults, whose immune systems are less effective, an example of the latter.
Both these groups, though, are already being enrolled in clinical trials for Covid-19 vaccines.
A Phase 1/2 clinical trial testing the Oxford University-AstraZeneca vaccine in South Africa includes an arm involving 50 people living with HIV. And a Phase 2b trial of Novavax’s candidate vaccine announced this week in the same nation will enroll 240 people who have HIV and who are medically stable. Under pressure from advocacy groups, Moderna recently amended its plans for its Phase 3 trial to include people with HIV as well.
As they have advanced to Phase 3 trials, various manufacturers testing vaccine in the U.S. have broadened their volunteer pools to include people 65 and older. Moncef Slaoui, co-chair of the administration’s Operation Warp Speed, said at a recent meeting of a National Academy of Sciences committee that the initiative requires all the vaccine projects it is funding to include older adults in their trials.
When asked if the trials are enrolling pregnant women, Slaoui said no.
The Food and Drug Administration indicated to manufacturers that it wanted testing in both these key groups to be conducted when it laid out its guidance for Covid-19 vaccines in June. But the agency stipulated that developmental and reproductive toxicity studies in animals should be conducted before candidate vaccines are tested in pregnant and lactating women.
At least one of the manufacturers, Pfizer, is in the process of conducting these trials, and will present the data to the FDA, a spokesperson for the company told STAT.
Other experts say there are encouraging signs.
Julie Ledgerwood, of the National Institute of Allergy and Infectious Disease’s Vaccine Research Center, said all of the manufacturers are having these types of discussions.
And Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland School of Medicine, said she believes “the paradigm has shifted.”
“I think most people feel that pregnant women should be included early. They have the capability of making informed decisions and deciding if they want to be part of a trial,” she said.
Larry Corey, co-leader of the National Institutes of Health’s Covid-19 Prevention Network, said ensuring the vaccines are safe for pregnant women “is of major importance” to the U.S. vaccine development effort.
“Engagement with regulatory agencies and the companies are underway to initiate such evaluations,” Corey, a vaccine expert at the Fred Hutchinson Cancer Research Center, said in an email. “Similarly, discussions are underway … to discuss plans for initiating studies in children.”
Outside of the U.S., two clinical trials of a Covid-19 vaccine candidate in China were open to children as young 6 months, according to the clinical trial registry ClinicalTrials.gov. No data from the trials have been published yet. A trial of a vaccine in India was allowing people aged 12 to 65 to enroll.
Then there is the Oxford-AstraZeneca Phase 2/3 trial, one arm of which is testing the safety of its vaccine in children aged 5 to 12. Neuzil, who is the other co-leader of the NIH network, said she expects more. “We have an expert group of pediatricians looking at this and it will be done in a careful age de-escalation manner,” she said.
Osterholm, who has been warning for weeks that the resumption of in-person schooling and the return of university students to campuses would fuel of surge of cases, thinks these studies cannot be done too soon. Already the University of North Carolina has reversed a decision to hold in-person classes after Covid-19 cases among students and staff quickly took off.
Opening schools and keeping them open will require children to be vaccinated, Osterholm said. “That’s why we’ve got to have safety data.”