While scientists are rushing to develop an immunization for adults, no one has started the process yet for children.
The pandemic has many parents asking two burning questions. First, when can I get a vaccine? And second, when can my kids get it? It may come as a surprise that the answers are not the same. Adults may be able to get a vaccine by next summer. But their kids will have to wait longer. Perhaps a lot longer.
Thanks to the U.S. government’s Operation Warp Speed and other programs, a number of Covid-19 vaccines for adults are already in advanced clinical trials. But no trials have yet begun in the United States to determine whether these vaccines are safe and effective for children.
“Right now I’m pretty worried that we won’t have a vaccine available for kids by the start of next school year,” said Dr. Evan Anderson, a pediatrician at Children’s Healthcare of Atlanta and a professor at the Emory University School of Medicine.
On Friday, Dr. Anderson and his colleagues published a commentary in the journal Clinical Infectious Diseases in which they called for vaccine makers to get their act together. They entitled it, “Warp Speed for Covid-19 Vaccines: Why are Children Stuck in Neutral?”
The search for a Covid-19 vaccine started as soon as researchers isolated the virus in January. Teams of developers across the world began creating vaccines based on different techniques. For example, some used inactivated coronaviruses that stimulated the immune system to make its own antibodies; others delivered viral genes into the body, triggering immune cells into action.
Once they were ready to test those vaccines, they started down a well-worn path of rigorous protocols developed over decades to determine if a vaccine is safe and effective. Vaccines require especially strict tests because they’re fundamentally different from drugs, which are intended for a limited number of people who are sick with some particular disease. Vaccines, on the other hand, are given to millions of healthy people to prevent them from getting sick in the first place.
After testing a vaccine on animals, developers start clinical trials on people. These trials come in three phases, going from small to large. Phase 1 and 2 trials let vaccine developers figure out which dose will likely be safest, while also delivering the best immune protection.
Phase 3 trials, the last stage in vaccine testing, are carried out on thousands or tens of thousands of volunteers. It’s during these studies that scientists can get clear evidence that a vaccine protects people from a disease. They can also reveal side effects that were missed by smaller studies.
Many vaccines — including ones for measles, polio, and tetanus — were designed from the outset to be given to children. In such cases, vaccine developers would typically start with trials in adults to check for any significant safety issues.
Only if researchers discovered no serious side effects would they start testing them in children, often beginning with teenagers, then working their way down to younger ages. Vaccine developers are keenly aware that children are not simply miniature adults. Their biology is different in ways that may affect the way vaccines work. Because their airways are smaller, for example, they can be vulnerable to low levels of inflammation that might be harmless to an adult.
These trials allow vaccine developers to adjust the dose to achieve the best immune protection with the lowest risk of side effects. The doses that adults and children need are sometimes different — children get smaller doses of hepatitis B vaccines, for example, but bigger doses for pertussis.
This process has proved safe and tremendously successful. In recent decades, childhood vaccines have saved millions of lives. Just expanding access to the measles vaccine alone led to a 78 percent decline in mortality between 2000 and 2008, preventing an estimated 12.7 million deaths worldwide.
In the past, the testing needed for Food and Drug Administration approval on a vaccine might have taken a decade or more. In recent years, researchers have pinpointed ways to accelerate their development while not sacrificing the research necessary to demonstrate they are safe and effective.
When the Covid-19 pandemic hit, some vaccine makers figured out how to combine phases, gathering more data in the same period of time. Governments and philanthropic organizations offered support for expensive clinical trials and for building factories to produce vaccines that had yet to prove themselves.
The result has been an unprecedented and swift march toward a vaccine. Just nine months into the pandemic, at least 38 Covid-19 vaccines have reached clinical trials, with dozens more slated to start in the months to come.
By the summer the earliest vaccines to go into clinical trials delivered promising results. The vaccines didn’t cause any serious side effects in the volunteers and produced promising levels of antibodies. At that point, they moved into Phase 3 trials.
Dr. Anderson said that vaccine makers could have started running trials for children over the summer, as soon as they had gotten good Phase 2 results from adults. But that did not happen. And with autumn around the corner, that still hasn’t happened.
Whenever these trials do start, it could take upward of a year to get vaccines for Covid-19 ready for children. Vaccine makers will need to write protocols and get them approved by the F.D.A. They’ll need to recruit volunteers — a process that is more time consuming for pediatric vaccines since parents must give informed consent. Getting to the first injections could take a couple of months.
By necessity, the trials would have to start small, with researchers giving perhaps just half a dozen kids a low dose of the vaccine and then monitoring them for several days. Then the trial could expand to dozens and then hundreds of kids.
A couple more months might pass while the vaccine developers give a low dose to a small group of kids. Each group of children would need two months of observation to check for their immune response and to make sure they don’t have any side effects. Only then would vaccine developers start a new trial with a higher dose.
These tests would likely start with older children, before researchers could shift down to kids between 3 and 8. And only after gathering early data from that trial would it be possible to start one for children under 3. Once all of the results from these trials came in, the F.D.A. would have to put them through an independent review before approving the vaccines for children.
There were good reasons behind the early focus on adults. Children are far less likely to die from Covid-19. On Friday, the Centers for Disease Control and Prevention issued a report which concluded that, of more than 190,000 people who died in the United States with Covid-19, only 121 were under the age of 21. Likewise, the rate of hospitalization in children under 18 is 20 times lower than it is in adults.
“As it stands, children are not a high-risk group,” said Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the F.D.A.’s vaccine advisory panel who was not involved with the new commentary. “Given limited time and resources to do these trials, I can understand why the initial focus is on those more than 18 years of age.”
Dr. Offit thought a reasonable time to start children’s trials might be after the first batch of approved vaccines rolls out for health care workers and other high-risk groups — perhaps in early 2021.
Dr. Kristin Oliver, a pediatrician and vaccine specialist at the Icahn School of Medicine at Mount Sinai, also thought that trials for children should wait — at least until one or more vaccines successfully pass Phase 3 trials. “We don’t know which one will make it through,” she said. “I’m super excited about a safe and effective vaccine, but I keep my excitement in check.”
But Dr. Anderson and his colleagues don’t want to wait so long. In their commentary, they said that Phase 2 trials on children “should begin now.”
They argued that even if a few hundred children die of Covid-19, those are deaths that could have been avoided with a vaccine. What’s more, there is a lot that doctors are learning about the impact of this new virus on children. In May, they discovered it can lead to an entirely new disease, called multisystem inflammatory syndrome in children, or MIS-C for short. Other long-term impacts of the virus on children remain to be seen.
AstraZeneca, Johnson & Johnson, Moderna and Pfizer all said that they were looking ahead toward developing a childhood vaccine.
“Moderna agrees with the importance and urgency associated with pediatric clinical trials for vaccines against Covid-19,” Ray Jordan, a spokesman for the company, said in an email. “We plan to start pediatric trials in the near future, subject to regulatory approval.”
Amy Rose, a spokeswoman for Pfizer said that the company is “actively working with regulators on a potential pediatric study plan to address the burden of disease in pediatric populations younger than 16.”
Dr. Anderson considered these statements as little more than vague promises and no substitute for real steps toward a pediatric vaccine. “In the meanwhile we are stuck in neutral with ongoing deaths and disease in children,” he said.
In addition to protecting the health of children, Dr. Anderson and his colleagues argued, a Covid-19 vaccine that might be ready by the start of the 2021 school year could slow the transmission of the virus among students, their parents and school staff. Vaccinating children could help reopen society, ensuring that schools do not become hot spots for superspreading events.
“They’re absolutely right,” said Dr. Grace Lee, the associate chief medical officer for Practice Innovation at Stanford Children’s Health and a professor of pediatrics at Stanford University School of Medicine. “In order for us to reopen effectively, we’re going to need vaccines for kids, period.”