Scientists Debunk Claims About Vaccine Safety Testing

Anti-vaccine activists, including prominent figures with ties to HHS Secretary Robert F. Kennedy Jr., continue to propagate the misleading narrative that childhood vaccines are unsafe because they haven’t undergone proper placebo-controlled testing. This claim fundamentally misunderstands the vaccine safety testing process and relies on an artificially narrow definition of what constitutes a placebo, according to scientific experts.

“Not a single childhood vaccine on the schedule has ever been through a double-blind placebo-based trial prior to licensure,” Del Bigtree, a prominent anti-vaccine activist, claimed at a March conference. Bigtree previously served as Kennedy’s communications director during his 2024 presidential run.

Kennedy himself has made similar assertions repeatedly. At an April congressional hearing, he stated, “With one exception, none of the 92 doses of 18 vaccines now given to our kids has ever gone through a randomized, controlled placebo trial.” He has claimed this absence of testing means “we do not know whether those vaccines are causing downstream effects.”

While these arguments might seem compelling to those unfamiliar with vaccine development, experts emphasize they misrepresent how vaccine safety is evaluated. All approved vaccines undergo rigorous safety testing, though this doesn’t always involve a saline-only placebo as Kennedy and others insist is necessary.

“Safety is not determined by any one study,” explains John Grabenstein, vaccinologist and director for scientific communications at the nonprofit Immunize.org. “It’s determined by the collection of all of the studies.”

Jeffrey S. Morris, director of biostatistics at the University of Pennsylvania’s Perelman School of Medicine, calls Kennedy’s claim that vaccine risk profiles remain unknown without placebo-controlled trials “clearly false” because it “dismisses all of the other studies and data that are present.”

Dr. Kathryn Edwards, a retired Vanderbilt University vaccinologist, notes, “Many of these vaccines have been given for a long, long time. Their safety profiles have been confirmed with observational studies involving millions of children.”

Under Kennedy’s leadership at HHS, this focus on narrowly defined placebo-controlled trials has begun influencing policy. The FDA recently indicated it would require new placebo-controlled trials for updated COVID-19 vaccines in lower-risk populations, and CDC officials cited a lack of placebo-controlled trials when cutting universally recommended childhood vaccines in January.

The Science of Placebo Controls

Anti-vaccine activists typically accept only saline (saltwater) as a legitimate placebo control. However, scientists consider other controls valid, including those containing inactive ingredients that match aspects of the vaccine’s formulation but lack the antigen—the key component that triggers immune protection.

These inactive ingredients can include stabilizers, preservatives, buffers, and trace manufacturing byproducts. “Even though it’s not a saline placebo, it is considered a valid placebo,” Morris explained.

The historical 1954 Salk polio vaccine trial, widely regarded as exemplary, used a reddish liquid identical to the vaccine but without killed polio virus as its placebo. This helped maintain “blinding”—keeping participants and researchers unaware of who received the actual vaccine.

Similarly, the chickenpox vaccine was tested against a placebo containing stabilizer and trace neomycin. Extensive studies involving approximately 11,000 participants followed for up to 12 years demonstrated the vaccine’s safety, with no severe side effects reported in healthy recipients. Two decades of post-marketing safety data have confirmed these findings.

Ethical Considerations

Scientists emphasize that there are sound ethical reasons why saline-only placebos aren’t always used in vaccine trials, especially with children.

“Often what you’re doing is comparing a new vaccine with an old vaccine,” Edwards explained. If a vaccine against a particular pathogen already exists, withholding protection from trial participants in a placebo group raises serious ethical concerns.

NYU medical ethicist Arthur Caplan and colleagues noted in a recent publication that placebo controls “are very rarely ethical in vaccine trials,” and are only permitted when there is genuine uncertainty about the vaccine’s benefit.

The FDA has specialized guidelines for clinical trials involving children that emphasize the need to “maximize benefit and minimize risk.” The agency has stated that a saline placebo “is not required to determine the safety (or effectiveness) of a vaccine” and in some cases would be “considered unethical.”

The Pneumococcal Vaccine Example

During a presentation to the CDC’s Advisory Committee on Immunization Practices, vaccine injury lawyer Aaron Siri highlighted the pneumococcal vaccine as an example of inadequate safety testing, noting that early versions were tested against an investigational vaccine rather than an inert control.

However, Dr. Steven Black, a pediatric infectious disease specialist who helped design the original Prevnar trial, explained this decision was made for sound ethical reasons.

“Subjecting what turned out to be half of more than 37,000 children to four injections—and these are infants and young children—with no potential benefit whatsoever was not ethical,” Black said. The decision to use an investigational meningococcal vaccine as a control was reviewed and approved by an independent ethics committee.

Black noted that the safety assessment in the Prevnar trial “was the most extensive of any safety evaluation for a phase 3 trial that had been conducted in the United States prior to that.” Medical professionals monitored all participants seeking medical attention to identify potential vaccine concerns, with serious events reported to the FDA.

The pneumococcal vaccine has since proven “extremely effective in reducing the risk of invasive pneumococcal disease in children” while also indirectly protecting older adults, Black added. “The number of lives saved has been tremendous. And serious confirmed safety concerns have not been identified despite millions of doses having been given.”

As the debate continues, vaccine safety experts emphasize that the rigorous testing and ongoing surveillance of vaccines provide robust evidence of their safety profile—regardless of whether they were initially tested against saline placebos or other appropriate controls.