The Casual Cruelty of Placebo-Controlled Trials

Robert F. Kennedy Jr. recently cast doubt on the validity of vaccine safety testing.

Anti-vaccine activists often tell the same story. Only the names of the vaccines, the materials in the vaccines, and the scientists who stand up for vaccines change. But the story remains the same. Government officials, pharmaceutical companies, public health agencies, scientists, and doctors are lying to you about vaccines. They are covering up safety problems. We, on the other hand, by pulling back the curtain on this conspiracy, will tell you the truth. Trust us. Not them.

A recent iteration of this story was told on an episode of Joe Rogan’s podcast. RFK Jr. informed Rogan’s listeners that pharmaceutical companies “never do placebo-controlled trials.” Therefore, because what companies have called “placebos” during pre-licensure trials might have themselves been unsafe, we never really know whether vaccines are safe before licensure. This claim was recently supported by a lawyer working for an anti-vaccine group ICAN, which stands for Informed Consent Action Network. As the word “Informed” implies, only ICAN will really inform you about vaccines.

ICAN’s lawyer wrote, “Robert F. Kennedy, Jr. is on record stating that almost all childhood vaccines were licensed based on clinical trials that did not include a placebo control. [Kennedy] is correct. A placebo is defined by the CDC as a ‘substance or treatment that has no effect on living beings.’ This means a saline injection or water drops in mouth.”

Let’s take a closer look at the ICAN lawyer’s claims. First, the CDC doesn’t regulate vaccines; the FDA does. When researchers at pharmaceutical companies consider human testing, they immediately submit their plans to the FDA, which defines placebo as “inert,” meaning immunologically inactive and harmless. The FDA would not allow any vaccine trials to proceed unless they deemed placebos to be true placebos. (There is one exception, which we’ll get to later.) However, the ICAN lawyer’s claim that vaccine trials didn’t use a placebo control doesn’t mean that vaccines are unsafe or that they don’t work. Indeed, post-licensure studies comparing children who did or didn’t get vaccinated have consistently shown that vaccines are safe and effective.

According to ICAN’s lawyer, the only substances that have “no effect on living beings” are water and salt water. Which is incorrect. Any chemical on this planet (both water and salt are chemicals) if given at a high enough dose, can be harmful. Drink 3-4 liters of water at one time, and you can suffer fatal water intoxication. Eat massive amounts of salt, and you can suffer fatal salt intoxication. In the words of Paracelsus, a 16^th century physician, “All things are poisons; for there is nothing without poisonous qualities. It is only the dose which makes a thing poison.”

ICAN’s lawyer argued that the only true placebos were water or saltwater, which isn’t true. Indeed, a wide range of placebos have been used in vaccine trials. These placebos might contain buffers, stabilizing agents, emulsifying agents, or adjuvants, like aluminum salts. They might contain sodium citrate, sodium phosphate, sucrose, or polysorbate-80. At the level contained in vaccines, all these chemicals are safe, including aluminum salts. Therefore, all meet the FDA criteria for a placebo.

Not all vaccine trials, however, are placebo controlled. As noted by ICAN’s lawyer: “Prevnar-13 was licensed based on a trial comparing it to Prevnar-7.” Prevnar-7, which was licensed in the United States in 2000, was designed to prevent seven of the most common types of pneumococci that cause pneumonia, meningitis, and bloodstream infections (sepsis), collectively referred to as invasive pneumococcal disease. Prior to the availability of Prevnar-7, pneumococci caused about 17,000 cases of invasive disease, 700 cases of meningitis, and 200 deaths in children less than 5 years of age every year. Prevnar-7 worked, clearly reducing the incidence of invasive disease. To further broaden protection, researchers developed Prevnar-13, which protected against an additional six types. ICAN’s lawyer apparently believes it would have been ethical to study Prevnar-13 pre-licensure with a water or saltwater placebo, knowing that a vaccine already existed that offered considerable protection against a severe and occasionally fatal bacterial infection. I can’t imagine how this kind of trial would have been explained to parents. Not surprisingly, according to a World Health Organization Advisory Panel, the study proposed by ICAN’s lawyer would have been unethical.

The casual cruelty expressed by ICAN’s lawyer can also be found in an event that occurred almost 70 years ago. In 1954, 420,000 first and second graders in the United States were inoculated with Jonas Salk’s inactivated polio vaccine; 200,000 were inoculated with salt water. It was one of the largest placebo-controlled trials of a medical product in history. Jonas Salk didn’t want to do it. He couldn’t conscience giving a saltwater shot to young children when as many as 50,000 were paralyzed by polio and 1,500 died every year. When the trial was over, the vaccine was declared “safe, effective, and potent.” Church bells rang out; synagogues held special prayer meetings; department store patrons stopped to listen to the results of the trial over loudspeakers. How did we know that Jonas Salk’s polio vaccine was effective? We knew because 16 children died from polio in that study—all in the placebo group. We knew because 34 of the 36 children paralyzed by polio in that study were in the placebo group. These are the gentle heroes we leave behind.

I suspect that none of the parents who volunteered for Jonas Salk’s polio vaccine trial were hoping their children were in the placebo group.