Yes, according to leading vaccine physician Paul Offit, who denounced the new placebo-controlled trial requirements for vaccines and sought greater clarity: “I don’t know what they’re talking about.”
Last week, the Department of Health and Human Services revealed new requirements for the approval of vaccines in what it called a “radical departure” from past practices. Vaccine experts were largely underwhelmed by the new policy and are seeking greater clarity from HHS.
In short, the agency will require all new vaccines to be tested in placebo-controlled trials before they are approved, several publications reported on April 30.
“What a shocking and novel concept,” quipped Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA’s Vaccines and Related Biological Products Advisory Committee. In all seriousness, Offit told BioSpace, there is “nothing novel about it. We’ve been doing that, really, near as I can tell, since 1940, so I don’t know what they’re talking about.”
In an email to BioSpace, an HHS spokesperson said that with the exception of the COVID-19 vaccine, “none of the vaccines on the CDC’s childhood recommended schedule was tested against an inert placebo, meaning we know very little about the actual risk profiles of these products.”
According to Offit, the key word here is “inert.” In a 2019 guidance document, HHS and FDA defined placebos as “inert substances with no pharmacologic activity.” But that does not appear to be the definition of today’s HHS under Secretary Robert F. Kennedy, Jr., Offit said. “Their definition is that anything that currently is not saline, being salt water, is not inert. So if it’s a buffering agent or stabilizing agent, then that’s not inert. . . . Their definition doesn’t conform to the FDA’s definition.”
Indeed, in a follow-up email, an HHS spokesperson told BioSpace, “An inert placebo is a substance with no active ingredients, such as a sugar pill or saline solution, used in clinical trials to measure the psychological or placebo effect of a treatment.”
William Moss, executive director of the International Vaccine Access Center and professor at Johns Hopkins Bloomberg School of Public Health, agreed that HHS is using a “narrow definition of placebo.”
Moss went a step further, telling BioSpace in an email that a placebo isn’t the only option for an effective vaccine trial. The comparison group could also include standard of care—when available—or even another vaccine that is not part of the routine immunization schedule so that the patient derives some benefit.
“To evaluate vaccine safety and efficacy, there needs to be a comparison group, but this does not need to be a group of children who receive an inert placebo,” he said.
The Consequences: Ethics and Access
Offit pointed to the long anti-vax history of Robert F. Kennedy Jr. and attorney Aaron Siri, who have “for years tried to argue that the childhood vaccine immunization schedule is unsafe, and it’s unsafe in ways that we don’t know about because we don’t do the right kinds of trials.”
On Tuesday, Offit penned an open letter to Sen. Bill Cassidy (R-LA), chairman of the U.S. Senate Committee on Health, Education, Labor and Pensions, recommending that Kennedy step down as HHS Secretary.
He’s not the first to recommend such drastic measures. In early April, following the sudden exit of Center for Biologics Evaluation and Research head Peter Marks, analysts at financial firm Cantor Fitzgerald appealed to President Donald Trump to do the same. A BioSpace poll at the time showed that many agreed this would be a good idea.
The new vaccine testing requirement is the latest in a long list of fireable offenses, according to Offit, whose letter also outlines Kennedy’s attempts to link vaccines with autism—a repeatedly debunked and dismissed theory—and spread misinformation about measles in the face of a “massive” national epidemic.
In a typical vaccine trial, a placebo can be “anything but the vaccine itself,” Offit said. Components of a vaccine include a buffer, stabilizing agent and adjuvants, plus the vaccine. “The vaccine group would be everything, and then the control group would be everything except the actual vaccine component. That enables you, in the event of adverse effects, to see whether or not it’s the vaccine that’s causing a problem.”
Moreover, Moss said there are ethical reasons for not using a placebo when evaluating vaccine safety in children. “It is unethical to give children an inert placebo when there already is an established vaccine with demonstrated effectiveness,” he said. Providing a control group with another vaccine “improves acceptability and achieves the basic principles of human subjects research: respect of persons, beneficence and justice.”
Meanwhile, Offit warned of potential delays to annual updates for critical vaccines. “Are they planning on doing a prospective, placebo-controlled trial with every new strain of COVID vaccine? It’s not practical. It would delay the availability of that vaccine to the point that . . . you would be leaving people vulnerable,” and possibly rendering that vaccine unusable or less effective because the virus has already evolved into new strains.
Last month, the FDA missed its PDUFA deadline for Novavax’s JN.1 COVID-19 vaccine. The product is an updated version of Nuvaxovid, which won emergency use authorization in July 2022 after four placebo-controlled trials. The JN.1 formulation has been under EUA since August 2024. On April 25, The Wall Street Journal reported that the FDA was requesting the company complete an additional randomized clinical trial.
Novavax has maintained that this would be a postmarketing commitment. However, FDA Commissioner Marty Makary recently wrote on X: “To be clear, this is a new product that Novavax is trying to introduce to the market with a study of a different product from 2021. New products require new clinical studies.”
In a Monday email to BioSpace, an HHS representative wrote that since Novavax is “seeking authorization for a new formulation targeting the JN.1 variant, the public deserves clear answers about its efficacy and if its benefits outweigh the risk. . . . Using the COVID pandemic as an eternal justification for blanket approvals of new products will not happen under the leadership of Commissioner Makary.”
But Offit said that conducting a new placebo-controlled trial for vaccines targeting different strains of COVID-19 “doesn’t make sense,” as the new formulations are based on the same technology that was used for the original vaccine—in Novavax’s case, a proprietary saponin-based Matrix-M adjuvant. An additional trial “will do nothing to improve efficacy,” Offit said. “It will do nothing to help with our understanding of safety profiles.”
Novavax declined to comment on the new requirements.
As for the vaccines on the CDC’s existing pediatric schedule, Offit was skeptical of a feasible path forward. “Are we going to go back and retest all the childhood vaccines against what they consider to be a placebo?” He also agreed with Moss that it wouldn’t be ethical, because many trial participants would not be given “vaccines that have been saving lives for the last 100 years. You can’t ethically do a prospective placebo-controlled trial with something that you know works.”
Transparency Wanted
News of the new HHS requirements first broke on April 30 through agency statements issued to The Washington Post and CNN. At this point, there is still no press release about the new policy on the agency’s website.
“Secretary Kennedy’s HHS has pledged radical transparency to the American public. This means being honest and straightforward about what we know—and what we don’t know—about medical products, including vaccines,” an HHS spokesperson wrote in an email to BioSpace last week.
For Offit, these two facts are discordant. “I think this is not a way to inform the press or the public or the industry,” he said. “They should spell out very clearly what they’re trying to do. But this is what happens when you have people who are not, I think, very knowledgeable about the process of vaccine research and development and manufacturing and production.”
In Offit’s view, “It’s just anti-vaccine activism come to the policy side.”
