How are vaccines tested?

Reuters

14-05-2025

May 14 (Reuters) - U.S. Health and Human Services Secretary Robert F. Kennedy Jr. plans to require all new vaccines be tested against a placebo in human trials, and has said that almost no shots used in the United States have undergone such rigorous testing, which is not accurate.
The American Academy of Pediatrics, opens new tab has said childhood vaccines are carefully studied in randomized controlled trials — including with placebos — to ensure they're safe and effective. Here is what you need to know about how vaccines are tested and approved in the United States:
What has Kennedy said about vaccine testing?
In an appearance with television personality Dr. Phil McGraw in April, Kennedy said that "the only vaccine that was ever safely tested in a clinical trial against a placebo was the COVID vaccine... None of the others were ever tested against placebo."
He repeated that claim during heated Congressional testimony on Wednesday.
What is a randomized controlled trial?
In order to receive approval from the U.S. Food and Drug Administration, most new medical treatments must be tested in large trials to confirm their effectiveness and safety.
In such trials, participants are randomly assigned to either a group receiving the new medicine or a control group. That ensures that any differences in outcomes can be attributed to the new treatment.
In many randomized trials, a new therapy is compared to an older, well established therapy. If no standard therapy already exists, the new treatment is compared to a placebo – an inert sham treatment without any therapeutic or physiological effect.
Are new vaccines always compared to placebos?
Not always. When a brand new vaccine is developed to protect against a disease that has no preventative therapy on the market, the FDA requires placebo-controlled trials to prove the vaccine is safe and effective.
Drugmakers also develop vaccines to improve upon an existing shot, either by updating an already-approved vaccine or by identifying a mechanism for defending against the virus that offers better protection and/or fewer side effects.
In those cases, the newer vaccine is compared to an existing vaccine. It is considered unethical to randomly assign volunteers to receive an inert placebo, leaving them – and the unvaccinated people they may come in contact with - vulnerable to a disease when a protective vaccine is available.
After successful testing in randomized controlled trials, all vaccines are then monitored in 'real world' studies, which usually include more diverse patient populations and reflect actual use in routine healthcare settings.
Have all childhood vaccines been tested against a placebo?
No. Childhood vaccines currently recommended for use in the United States that have been tested against placebos include Sanofi's (SASY.PA), opens new tab Daptacel, used to protect against diphtheria, tetanus, and pertussis (whooping cough), Sanofi's immunization against respiratory syncytial virus (RSV) Beyfortus, and GSK's Rotarix and Merck's (MRK.N), opens new tab RotaTeq, the two rotavirus vaccines licensed for use in the United States.
Some of the currently available vaccines were tested by comparing them to already-approved vaccines.
For example, the very first combined vaccine against measles, mumps and rubella (MMR), approved in 1971, was compared in randomized controlled trials to a measles-only vaccine and a placebo. But most subsequent MMR vaccines were not compared to placebos because that would have left study participants vulnerable to preventable diseases.
What do experts say about Kennedy's proposal?
Kennedy's proposal to require that all new vaccines undergo safety testing in placebo-controlled trials 'is ethically problematic and will slow testing down for no good reason,' Dr. Seema Shah, director of research ethics at Ann & Robert H. Lurie Children's Hospital of Chicago, said in a statement.