US Health and Human Services Secretary Robert F. Kennedy Jr. has repeatedly claimed in public statements that most vaccines recommended for children in the US have not been tested against placebos, and particularly inert placebos such as saline solution or water.
“The only vaccine that has been tested in a full-blown placebo trial against an inert placebo was the Covid vaccine,” Kennedy said May 14 in testimony before the US Senate’s Health, Labor, Education and Pensions Committee.
“The other 76 shots that children in this country received between birth and 18 years old, none of them have been safety tested in prelicensing studies against the placebo, which means we don’t understand the risk profile for those products, and that’s something I intend to remedy,” he told Sen. Chris Murphy, D-Connecticut.
In 2023, Kennedy told Fox News host Jesse Watters: “Vaccines are exempt from prelicensing placebo-controlled trials, so that there’s no way that anybody can tell the risk profile of those products or even the relative benefits of those products before they’re mandated. And we should have that kind of testing.”
HHS is acting on Kennedy’s claims, too. The department recently announced it will require all new vaccines be tested in placebo-controlled trials before they’re licensed for use, a change it called “a radical departure from past practices.”
These claims made Dr. Jake Scott’s ears perk up. Scott, an infectious disease specialist at Stanford University, knew that the assertions couldn’t be true, and now he says he has the proof.
Scott launched a project in April to round up every randomized, placebo-controlled clinical trial of vaccines in the medical literature, including studies run in other countries, since some vaccines used in the US are tested overseas.
It took five weeks to arrive at a number: There have been 258 placebo-controlled clinical trials of vaccines, according to Scott and a team of volunteers who scoured databases of medical literature. More than half of those studies tested vaccines against inert placebos.
Based on Scott’s research, at least nine of the 16 vaccines that are routinely recommended by the US Centers for Disease Control and Prevention for children have been tested against inert placebos, while several more have been tested against active placebos.
In scientific research, randomized, placebo-controlled clinical trials are considered to generate the highest-quality evidence. That’s because they split their study participants into equal groups; some get the study intervention or treatment, while others get a placebo or dummy remedy.
Placebos are often carefully designed to look, taste or even smell like the intervention that’s being tested. The idea is to keep both the participants and the researchers themselves in the dark about who’s getting the real thing until the end of the study, when the results are analyzed and reported, to prevent any potential bias.
Crowdsourcing vaccine research
On April 22, Scott posted a link to a shared Google spreadsheet online, along with some ground rules about which trials could and couldn’t be included. The studies had to be in humans; no animal studies or lab-only investigations allowed. The researchers also used a particular set of search terms, with no limits on dates, languages or pathogens. The team then read each study that was found to make sure it met the specified criteria for inclusion in the review.
“It took off,” Scott said. He estimates that the project had five or six core contributors, but they had help from around the world.
Together, they scoured PubMed, the database of medical research maintained by the National Library of Medicine, as well as reference lists from Cochrane, the World Health Organization and the CDC.
Dr. Isaac Bogoch, an infectious disease specialist at the University of Toronto, said he was blown away when he saw the final list of studies, which included about 2.5 million participants in total.
“The body of evidence for many of the vaccines that we use is very impressive, and the data is robust,” said Bogoch, who didn’t contribute to the project. “This type of work is extremely important in era of unprecedented vaccine hesitancy.”
A ‘demonstrably false’ claim
Scott said the research proves that Kennedy’s statements are “demonstrably false.”
To understand why, it’s useful to break down the parts of Kennedy’s argument, which he has repeated in different iterations for years.
Kennedy has shifted the goalposts, but there are a few things he has said would make a clinical trial meet his requirements: First, an inert placebo, meaning a placebo control that didn’t have any biological effects on the body, like water or saline solution. Kennedy has said that without comparison to an inert placebo, the true side effects of vaccines can’t be fully understood.
He also uses the term “prelicensing,” meaning the research is conducted before the US Food and Drug Administration has approved the vaccines. The FDA sometimes accepts enough evidence to approve a vaccine but then will require more safety studies and monitoring after approval. Kennedy and other critics argue that more safety testing should be done before the vaccines are approved in the first place.
In some instances, Kennedy has also said that these studies should be large, including many participants, and long-running. In general, larger studies have greater statistical power to show subtle differences between groups. And the longer a trial follows its participants, the more confident researchers can be in the durability of their results.
Although scientists agree that larger and longer clinical trials are the most reliable, these studies are expensive to conduct. They can take years to run, which delays the possibility of getting an effective intervention to people. It can also be difficult to find participants who can stick with the monitoring requirements of a study for longer periods of time.
In recent testimony, however, even Kennedy seemed to be softening his stance on this particular stipulation, agreeing that other types of studies can provide solid evidence, too.
“You know that the Cochrane Collaboration in 2016 published a study that showed that the predictive capacity of placebo-controlled trials, which are the gold standard, is actually not any better than good observational trials in retrospective trials. So we can do those kind of studies without subjecting people to an unethical experiment,” Kennedy said during a May 20 Senate budget hearing when asked about the need to test established vaccines in large, lengthy placebo-controlled trials.
In his 2021 book, “The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health,” Kennedy repeats the claim that vaccines for children haven’t been tested against inert placebos, saying that he and groups he’s affiliated with have explicitly asked to be shown such studies. He cites two letters between the Informed Consent Action Network or ICAN, a group run by his close associate Del Bigtree, and HHS.
The letter from ICAN asserts that in contrast to most other FDA-approved medications, “vaccines are not required to undergo long-term double-blind inert-placebo controlled trials to assess safety. In fact, not a single one of the clinical trials for vaccines given to babies and toddlers had a control group receiving an inert placebo.”
The HHS letter refutes this claim: “Contrary to statements made on page two of your letter, many pediatric vaccines have been investigated in clinical trials that included a placebo.” The letter goes on to say inert placebos are not necessary to understand the safety of a new vaccine, and so they haven’t been required.
Still, Scott says the evidence is clear: Of the 258 placebo-controlled vaccine studies he and his colleagues found, about half – 128 – included inert placebos.
When it comes to vaccines routinely recommended for children, specifically, Scott found that at least nine of the 16 on the CDC’s regular schedule have been tested against inert placebos: These are the vaccines against Covid-19; rotavirus; polio; influenza; measles, mumps and rubella; human papillomavirus; varicella, or chickenpox; pneumococcal; and H-flu, or Haemophilus influenzae.
One of the largest of these trials was on the polio vaccine. The placebo-controlled part of the study included more than 400,000 grade-schoolers. Half got the inactivated polio vaccine created by Dr. Jonas Salk, and the other half were given injections of an inert placebo, which was saline solution.
The trial was conducted in 1954, and the results were announced in April 1955. So great was the urgency to get the vaccine to kids that the FDA licensed it the same day.
Scott says he and his colleagues hope to have their project published in peer-reviewed medical journal soon. For now, it’s available in a publicly posted spreadsheet.
Active vs. inert placebos
Vaccine trials that don’t use inert placebos will sometimes use what are known as active placebos. These comparison shots have some biological effect but don’t interfere with scientists’ ability to interpret the results of their study.
Active placebos are used for a variety of reasons. In some parts of the world, for example, where it might be difficult to recruit participants, researchers might give the control group an unrelated vaccine to make sure they’re getting some benefit by enrolling in the study.
One study published last year in the Lancet, testing a vaccine against malaria, gave participants in the control group a vaccine against rabies instead. Rabies vaccines don’t protect against malaria, so they wouldn’t interfere with researchers’ ability to tell whether the malaria shot actually worked.
Other active placebos in the studies in Scott’s project included shots that contained only an adjuvant, an ingredient that’s added to vaccines to trigger a stronger immune response.
Dr. Greg Poland, who studies how adults and children respond to vaccines at the Mayo Clinic, said it would be a mistake to assume that active placebos can’t be valid and rigorous ways to test vaccines.
Adjuvants, such as aluminum, are often the reason people get soreness around an injection site. Giving just the adjuvant can guard against even psychological bias in control participants who might guess that they didn’t get a real vaccine if they didn’t feel anything after their shots. It also allows researchers to isolate the benefits and side effects of the vaccine proteins, since everyone got the adjuvant.
“You’re literally saying, ‘OK, we’re testing a vaccine that has ingredient A plus B against a non-vaccine placebo that has ingredient B.’ So the only thing different between the two of them is the actual vaccine,” Poland said.
An active comparator might also be used rather than an inert placebo because of ethics. When there’s already a vaccine that’s considered to be safe and effective against an infection, it’s considered unethical to deny study participants the chance to get it. In that case, companies that want to test a new and improved version of a vaccine against an older one would normally have to offer participants in their control group the older vaccine. Many modern vaccines have been compared against older versions of the same vaccine.
Flu vaccines are a good example, Poland says. If you were testing an improved type of flu vaccine, chances are that the board that oversees your clinical trial wouldn’t approve a study that used an inert placebo – especially if you were testing it in a vulnerable group, like people over 65, for whom an infection is more likely to be dangerous.
“It’s unethical because the recommendation is that everyone, each flu season, receive an influenza vaccine. So it’d be unethical to enroll people in a study where they may just get placebo and not get any benefit of protection,” Poland said.
Poland said he’s been puzzled by Kennedy’s statements, too. He’s concerned that they are getting traction with the public now that Kennedy is the head of the nation’s health agencies.
“This notion that there are no placebo-controlled vaccine trials is patently false, but it’s a really interesting phenomenon that I have a hard time understanding,” he said.