FDA Officials Detail Plan to Limit COVID Shots

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New policy moves toward a risk-based approach

by
Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today
May 20, 2025 • 3 min read

FDA officials have outlined their new approach to COVID-19 vaccine approvals, allowing immunogenicity endpoints for high-risk groups, while calling for randomized controlled trials for those at lower risk.

FDA Commissioner Marty Makary, MD, MPH, and Center for Biologics Evaluation and Research Director Vinay Prasad, MD, MPH, detailed the new framework in a “Sounding Board” piece in the New England Journal of Medicine.

The agency will allow immunogenicity data to approve COVID shots for adults ages 65 and up, and for all people 6 months and up who have one or more risk factors for severe disease, Makary and Prasad wrote.

However, randomized controlled trials will be recommended for those ages 6 months to 64 years who are considered healthy. The agency will “encourage” these trials as part of a postmarketing commitment for approvals in high-risk groups.

The ideal population for these trials is 50- to 64-year-olds, as there’s “equipoise about yearly boosters” for this group, Makary and Prasad wrote. The preferred primary endpoint will be symptomatic COVID. In addition, controls should receive a saline placebo, people who’ve had COVID in the last year shouldn’t be excluded, and trials should run for 6 months, they noted. Secondary endpoints will include severe disease, hospitalization, and death.

Makary and Prasad noted that the pathway ensures timely access to a broad population, since the list of comorbid conditions is long, with an estimated 100 to 200 million Americans having access to COVID shots.

Among the reasons they listed for the change in policy was that the U.S. has “the most aggressive” COVID vaccination policy when compared with European countries, which have mostly adopted a risk-based strategy.

U.S. vaccine advisors have indeed been considering a switch to a risk-based approach as well, which was discussed at the CDC’s Advisory Committee on Immunization Practices meeting last month.

The FDA also gave full approval to the Novavax COVID vaccine (Nuvaxovid) using this approach, approving it for those ages 65 and up, along with people ages 12 and up who have at least one underlying condition that puts them at risk of severe disease.

FDA also required Novavax to conduct postmarketing studies on the risks of myocarditis and pericarditis with the vaccine, and requested a new postmarketing study in people ages 50 to 64 who aren’t at risk for severe disease.

Paul Offit, MD, of the Children’s Hospital of Philadelphia, warned that answers to many of the issues raised by the FDA’s new framework are already known.

“If you’re looking for protection against any symptomatic illness in 50- to 64-year-olds, I think we already know that antibodies wane and 4 to 6 months later you will once again be susceptible to mild-to-moderate illness,” Offit said. “We know it’s a short incubation, and mucosal infection protection against mild-to-moderate disease is mediated by antibodies in the circulation at the time of exposure.”

He also noted that to assess a severe disease endpoint in this age group, “you’d have to do a fairly big study,” since the outcome will not be frequent.

As for safety, he pointed out that COVID shots have now been given to “hundreds of millions of people. Do we not feel we have a pretty good idea of the safety profile of the vaccine at this point?”

“I think we know about its rare adverse events,” he said. “I am not sure that a study is going to be big enough to really tell you about a safety event we don’t already know about.”

Finally, Offit questioned whether such a trial is ethical, given that the U.S. has seen 300,000 hospitalizations and 30,000 deaths from COVID this year. “Knowing that this vaccine works and that the virus still circulates, can you still really have a group that doesn’t get the vaccine, ethically speaking?”