After Pfizer’s vaccine had been approved for 12- to 15-year-olds, I got a lot of emails. As a member of the FDA’s Vaccine Advisory Committee, people wanted to tell me what they thought of the decision. Most argued that the vaccine hadn’t been tested long enough or in enough children to know it was safe.
I told them Pfizer had studied 2,360 children; half had received two doses of mRNA vaccine; the other half had received a placebo vaccine. Children were followed for several months. When the trial was finished, 18 children had suffered COVID-19, all in the placebo group.
For some, this trial was too small. They wanted to know why Pfizer hadn’t done a study similar in size to the one it had done in 40,000 adults? And why hadn’t these younger children been studied for a longer period of time? Had we really learned enough from the adult vaccine trials to feel comfortable that we would find the same results in children?
Or, said another way, what human price were we willing to pay for greater certainty? Because there is always a price, perhaps none greater than that paid during the polio vaccine trials.
`Safe, potent, and effective’
In the late 1940s and early 1950s, Jonas Salk made a polio vaccine by growing the virus in monkey kidney cells, purifying it, and inactivating it with the chemical formaldehyde. He tested his vaccine in about 700 children in the Pittsburgh area, finding it to be safe and highly immunogenic. But he hadn’t yet proved that it worked. To do that, Thomas Francis at the University of Michigan conducted the largest clinical trial of a medical product in history. The trial broke Salk’s heart. He couldn’t accept withholding his vaccine knowing that polio paralyzed as many as 30,000 children every year in the United States and killed 1,500.
Between 1954 and 1955, 420,000 first and second graders were given Salk’s polio vaccine, 200,000 were given a placebo vaccine, and 1.2 million served as observed, uninoculated controls. When the trial ended, in April 1955, Francis stepped to the lectern in Rackham Hall at the University of Michigan and said four words that became a headline in every newspaper in the country: “safe, potent, and effective.”
How did Francis know that Salk’s vaccine was effective? He knew it because 16 children died from polio during the study — all in the placebo group. And he knew it because 36 children were paralyzed during the study — 34 in the placebo group. But for the flip of a coin, most if not all these children could have lived long, healthy lives. Such was the price of knowledge.
`When did we know enough?’
One could reasonably argue that polio virus was like a yearly, worldwide pandemic. And that approving Salk’s vaccine by emergency use authorization prior to the trial would have prevented tens of thousands of children from being paralyzed and hundreds from dying during the year that the vaccine was tested. For polio vaccine researchers in the 1950s, the question was “When did we know enough?”
If instead of doing a 2,300-child trial of its mRNA vaccine in 12- to 15-year-olds, Pfizer had done a 23,000-person trial, as was suggested by some of the emails I received, then it wouldn’t have been 18 children in the placebo group that had suffered COVID-19, it would have been 180. And if Pfizer had chosen to study these children for a few years instead of a few months, thousands of children in this age group would have suffered from COVID-19 unnecessarily.
More than 400 children have died from COVID-19. And thousands have suffered a disease called MIS-C, which causes damage to a variety of organs including the lungs, liver, kidneys, and heart. Many of these children have suffered symptoms that have lasted longer than 56 days: so-called long haulers. SARS-CoV-2 is a winter virus. Come late fall and early winter — given that many areas in this country are severely undervaccinated — the United States will likely see a surge of hospitalizations and deaths from this virus. This, combined with a delta variant that is the most contagious to date, and that many schools in the Philadelphia area have opened for in-person learning while struggling to enforce masking and social distancing, will make young children particularly vulnerable.
When will we have enough data in young children to feel comfortable? Remember, there are no risk-free choices. Just choices to take different, and perhaps greater, risks.
Paul A. Offit, M.D., is a professor of pediatrics at the Children’s Hospital of Philadelphia, a member of the FDA’s Vaccine Advisory Committee, and the author of You Bet Your Life: From Blood Transfusions to Mass Vaccinations — The Long, Risky History of Medical Innovations (Basic Books, September 2021).