This article was modified on May 22 to clarify some points.
Originally published by our sister publication Infectious Disease Special Edition
By Fran Krtiz
With On May 20, the FDA announced a new regulatory framework for COVID-19 vaccines that restricts access to the shots to older adults and younger people who have at least one risk factor for severe disease.
“The FDA anticipates that it will be able to make favorable benefit–risk findings for adults over the age of 65 years and for all persons above the age of 6 months with one or more risk factors that put them at high risk for severe Covid-19 outcomes as described by the CDC (Figure 2),” wrote FDA Commissioner Marty Makary, MD, and Center for Biologics Evaluation and Research (CBER) Director Vinayak Prasad, MD, in a commentary published in The New England Journal of Medicine (2025 May 20. doi:10.1056/NEJMsb2506929).
Questions remain about the framework, including whether it applies to vaccines already on the market, whether pediatric doses will remain on the market, and whether insurers will cover vaccines for people who are younger and do not have risk factors.
The FDA is also talking about clinical trials for the vaccines, writing in the commentary that “for all healthy persons—those with no risk factors for severe Covid-19—between the ages of 6 months and 64 years, the FDA anticipates the need for randomized, controlled trial data evaluating clinical outcomes before Biologics License Applications can be granted.”
Drs. Makary and Prasad added that even when approving a COVID-19 vaccine for high-risk groups, “the FDA will encourage manufacturers to conduct randomized, controlled trials in the population of healthy adults as part of their post marketing commitment.”
When trials would become necessary was not clear. The NEJM article refers to “moving forward.” Jesse Goodman, MD, MPH, a former FDA chief scientist and now a professor at Georgetown University, in Washington, D.C., said during a reporter briefing on Wednesday that while the FDA's policy is not yet fully clear, it appears the agency may be proposing a requirement for new placebo-controlled trials in those younger than 65 without risk factors when manufacturers introduce new vaccines or, in some cases, modify vaccines to protect against a new circulating strain. Dr. Goodman pointed out that while he agrees that the risks from COVID-19 to healthy younger people are now much lower than early in the pandemic, multiple controlled trials performed previously have already shown benefit to them from vaccination.
But Paul Offit, MD, the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told Infectious Disease Special Edition that such placebo-controlled trials at this point “would not be ethical.
“The virus is still circulating and causes hospitalizations and deaths, and people 50 to 64 are not at no risk, [so it is unethical] to give a placebo when you know the vaccine works,” Dr. Offit explained.
Dr. Goodman agreed with FDA that updating the understanding of vaccine benefits in such individuals, and considering those findings in updating recommendations for vaccine use, is desirable but felt that could be achievable throug carefully conducted observational studies looking at large numbers of people using healthcare databases.
Infectious disease experts said the process the FDA has employed for the decision about the vaccines is a sharp departure from the long-established practices for vaccine review, approval and recommendations. “Judging by the many emails and phone calls, the move surprised many in the infectious disease community,” said William Schaffner, MD, an infectious disease specialist at the Vanderbilt University School of Medicine, in Nashville, Tenn. “This seems to be the FDA usurping the roles of both the FDA's VRBPAC [Vaccines and Related Biological Products Advisory Committee} advisory committee and the CDC's ACIP [Advisory Committee on Immunization Practices] committee,” Dr. Schaffner said. VRBPAC, of which Dr. Offit is a member, traditionally advises the FDA before approvals but instead will be meeting on Thursday after the agency’s COVID vaccine announcement.
The ACIP, which will meet in June, is the entity that traditionally has made the recommendations for those who should get a vaccine, Dr. Schaffner said, although documents from an April 2025 ACIP meeting suggested they were reviewing whether to change the recommendations.
Often, however, Dr. Schaffner said, the ACIP and then the CDC say people who fall outside the specifically recommended groups can talk to their doctor about whether the vaccine is appropriate for them, a proviso that often makes insurers cover the vaccines for people outside the specified groups. It’s not known yet whether the ACIP or CDC will add that consideration, which means it’s unknown if insurers will cover the vaccine for, as an example, a person who wants to get the vaccine to avoid giving COVID to someone at risk in their family or friend group, Dr. Schaffner said.
Robert Hopkins, MD, the medical director of the National Foundation for Infectious Diseases, said he has additional concerns about the FDA announcement, including:
- What is the potential role of vaccines in preventing long COVID, which remains an ongoing public health challenge?
- Will self-reporting of risk factors still be an option for a person being vaccinated or would additional verification be required at the vaccination site? “This could be an implementation nightmare,” Dr. Hopkins said.
- The risk remains that a new, more transmissible or severe virus variant could emerge, he added. If that happens, limited access to vaccination could leave the nation vulnerable—not only medically, but also in terms of the demand on our healthcare system and the broader social and economic impacts.