Vaccines are key to keeping ourselves and our world healthy. Most people have received at least one vaccine in their lifetime, but few know exactly how their safety is determined.
In the U.S., vaccines go through many stages of safety testing before they are approved, as well as additional safety monitoring for as long as they are on the market. Additionally, researchers worldwide study any possible link between vaccines and health issues.
“Vaccines are always being tested for safety because they have to be,” said Dr. Paul Offit, a pediatrician and vaccine researcher, in a 2015 Children’s Hospital of Philadelphia video. “We’re giving them to healthy children, so they need to be held to frankly the highest standard of safety.”
The ethics of safety testing vaccines
A common misconception about vaccines is that they are not tested against a placebo, a fake treatment given to compare the effects of the real treatment. In reality, all routine vaccines are tested against some type of placebo, but not all placebos are the same.
Many new vaccines are tested against a saline placebo, or saltwater solution. Like sugar pills used in many drug studies, saline placebos don’t cause a reaction.
Some vaccines are tested against an active placebo. These contain most vaccine ingredients but lack the antigen, which teaches your immune system to recognize and fight disease.
Active placebos allow researchers to distinguish between side effects caused by antigens or other vaccine ingredients. But when a vaccine is already available, depriving a child of it to test a new vaccine is considered unethical. Instead, the new vaccine is tested against an existing one to compare safety.
Finding a vaccine target
The first stage of vaccine development is identifying a target for the antigen. An ideal vaccine antigen can trigger an immune response without causing serious side effects. Once a potential antigen is identified, it is tested for safety and effectiveness.
Research in animals and cells
New vaccines must be thoroughly tested before human studies begin. These tests, called preclinical studies, are performed in animals and human cells.
Preclinical studies allow researchers to determine whether a vaccine is effective while flagging potential safety issues. If a new vaccine shows safety concerns in preclinical research, it will not advance to human studies.
Clinical trials in humans
After a vaccine has been found to be safe and effective in preclinical studies, researchers must get permission from the Food and Drug Administration to begin clinical trials in humans. These trials are divided into three progressively larger ones that all test for safety.
Phase 1
The Phase 1 trial is the smallest, typically with fewer than 100 participants. This first clinical trial aims to determine the vaccine’s general safety.
Phase 2
Phase 2 trials are larger than Phase 1, typically involving a few hundred to a few thousand participants. These studies screen for common side effects and determine whether the vaccine is effective.
Phase 3
As the largest of the three trials, Phase 3 vaccine studies can include thousands of participants and vary widely in size. These trials test for continued safety, effectiveness, and appropriate dose.
FDA approval
After clinical trials are complete, federal health officials review the safety data to determine if the vaccine should be approved. The FDA makes the final approval decision, and the Centers for Disease Control and Prevention’s advisory committee makes recommendations on how approved vaccines should be used.
Post-approval safety monitoring
Research into vaccine safety doesn’t end once a vaccine is approved. Vaccine makers conduct Phase 4 trials to continue studying the safety of vaccines in larger and more diverse populations. Additionally, research initiatives like Johns Hopkins University’s Institute for Vaccine Safety, the Global Vaccine Data Network, and the Brighton Collaboration work to understand and improve the safety of all vaccines.
The U.S. has multiple safety monitoring systems to identify adverse reactions that are too rare to be detected in clinical trials.
“[Adverse] events that are one in a million, one in 100 million obviously cannot be done in a [clinical trial] format and require vigorous surveillance systems when larger scale use is deployed,” said Stephen Morrissey, executive managing editor of the New England Journal of Medicine.
The CDC and FDA oversee the Vaccine Adverse Event Reporting System (VAERS), which allows anyone to report a health issue after vaccination. The agencies closely monitor these reports and investigate health concerns that occur more often than expected. Health officials promptly alert health care providers and the public when a potential safety concern is detected.
VAERS can detect extremely rare potential side effects. However, because the data is not verified, it cannot be used to determine whether a specific vaccine caused a specific adverse reaction.
V-safe is a vaccine safety system that allows people to report how they feel after getting certain vaccines, including any side effects. V-safe has collected vaccine experience and safety data from over 10 million people.
The Vaccine Safety Datalink is a collaboration between the CDC and 13 health care organizations in nine states that monitor and research vaccine safety. These organizations conduct large-scale research into rare and serious potential vaccine safety concerns, which helps inform vaccine recommendations.
The Clinical Immunization Safety Assessment Project is a network of vaccine safety experts who conduct vaccine safety research and provide guidance to health care providers on vaccine safety.
These initiatives and systems bring together thousands of scientists, public health experts, and health care providers who work to ensure that all authorized and approved vaccines are safe for as long as they are in use.
For more information about vaccine safety, talk to your health care provider.