What is the deal with placebo trials?

Public figures, including HHS Secretary Kennedy Jr. and some politicians and social media accounts, shared the idea that childhood vaccines in the U.S. were never tested in long-term, placebo-controlled trials. Their posts and interviews helped the claim spread widely on platforms like Twitter and in news stories. This idea was mentioned in ACIP meetings, public hearings, and across social media in 2025, making it a common talking point among anti-vaccine groups and influencers.

A placebo is something used for comparison in a study. Many people think a placebo must always be saline (salt water), but that is not always true. An inert placebo (like saline) has no active ingredients.

An active control may contain something already known to be safe, like another vaccine or vaccine ingredients such as stabilizers or adjuvants (ingredients that help the vaccine work better). These added ingredients make sure that the person getting the vaccine or placebo cannot tell which one they actually received. If they could tell, it might change how they describe their symptoms to the scientists in charge of the trial

Both types are accepted in science, depending on the situation. And despite what some people claim, many childhood vaccines were tested using saline placebos, including vaccines for:

• Rubella vaccine
• Pneumococcal vaccine
• Hib vaccines
• HPV vaccine
• The Salk Polio vaccine
• Measles vaccine
• Tdap vaccine
• COVID vaccine

These trials looked at both safety (does it cause harm?) and effectiveness (does it prevent disease?).

The World Health Organization (WHO) gives guidance on when placebos should be used. Using a saline placebo is ethical when no effective vaccine already exists. But if a safe and effective vaccine is already available, it can be unethical to give some people an inert placebo. Doing so would leave them unprotected against a serious disease, even though we know they could get hurt.

A good example is the pneumococcal vaccine. Prevnar-13 was tested against Prevnar-7, an older vaccine that already worked. Using saline instead would have meant leaving children unprotected against dangerous bacterial infections. That would have put children at real risk of serious illness or death.

In these cases, scientists compare the new vaccine to an older one to make sure it works as well or better, while still keeping people safe.

Why not just use saline placebos? The answer is simple: babies are vulnerable. When scientists already know a vaccine prevents serious disease, they do not want to leave some babies unprotected just to satisfy a study design.

Instead, researchers:

• Compare new vaccines to trusted older ones
• Track safety through long-term studies
• Monitor millions of real-world doses after approval

Vaccines are tested for many years. For example, the hepatitis B vaccine was tested on thousands of people before it was given to newborns. Scientists looked carefully for both short-term and long-term side effects.

Some also claim that the hepatitis B vaccines were only tested for five days. They came up with this idea from reading vaccine package inserts, which are legal documents, not full research reports. The “five days” only referred to watching for mild problems at the injection site, like a sore leg. Serious health problems were tracked for months, and other symptoms like fever were tracked for weeks.

Hepatitis B can cause lifelong infection, liver damage, and liver cancer. The younger someone is when infected, the more likely it is to become chronic. There is no cure, but the vaccine can prevent it. That is why protecting infants early is so important.

Science does not rely on rumors or shortcuts. It relies on careful testing, ethical rules, and ongoing safety monitoring.