How Reactions Are EvaluatedBefore a vaccine is put into standard medical practice, it must be studied in clinical trials of thousands of people, which allows for evaluation of relatively common side effects. For example, a common side effect might occur in one or more of several hundred vaccine recipients. But rare events (fewer than one case in several thousand recipients) aren't usually evident in clinical trials. "Unless you've studied something in a million or more people, you might never see the very rare event or be able to know whether it occurred due to vaccination or simply by chance," Goodman says.
Through the Vaccine Adverse Event Reporting System (VAERS), jointly operated by the FDA and the CDC to monitor the safety of licensed vaccines, experts look for patterns and any unusual trends that may raise questions about a vaccine's safety once it is used more widely in the population. The FDA continuously reviews and evaluates individual reports, in addition to monitoring overall reporting patterns. The FDA also monitors reporting trends for individual vaccine lots. Most reports come from health-care providers, but anyone can report an unexpected event after vaccination to VAERS. (See "Steps to Take When You Vaccinate" for the VAERS toll-free number.)
VAERS receives 800 to 1,000 reports each month. Because it often can't be determined whether an adverse event occurring after vaccination was actually caused by the vaccination, health-care providers and consumers are encouraged to report any event that might be attributable to a vaccine.
"You don't have to be sure," says Susan Ellenberg, Ph.D., director of CBER's office of biostatistics and epidemiology. "Reporting possible reactions will help identify adverse events that might be truly associated with vaccinations and need further study." But this approach to reporting means that one can't assume that all VAERS reports describe true vaccination reactions.
VAERS is a passive, voluntary reporting system, which means not all adverse events get reported. It also means that many reports are incomplete or even contain inaccurate information because the forms are not filled out by trained personnel. Another problem with interpreting VAERS data is the lack of information on the total number of individuals who received a particular vaccine, making it impossible to estimate the incidence of reported adverse events. It's also often the case that multiple vaccines are given at the same time, further complicating the interpretation of what might have caused the event, Ellenberg says.
Despite these problems, VAERS does contribute in important ways to understanding vaccine safety. VAERS data may suggest the need for more research on certain vaccines. "In this sense, VAERS is a signal generator," Egan says. Recently, VAERS data were instrumental in evaluating RotaShield, a vaccine licensed to protect against rotavirus infection. Rotavirus is the most common cause of gastroenteritis in children younger than five and can result in severe diarrhea, dehydration, and death. This virus is an especially serious problem in developing nations, where it kills hundreds of thousands of children every year. Following the vaccine's licensure, VAERS started to receive reports of bowel obstruction in a number of infants who had received RotaShield. Careful review of these reports revealed that the bowel obstruction occurred most often in the first two weeks after RotaShield was administered. As a result, the CDC recommended postponing any further distribution or administration of RotaShield until more data could be collected and evaluated.
The FDA discussed the concerns with the manufacturer, which decided to voluntarily withdraw the product from use. In November 1999, ACIP withdrew its previous recommendation for universal use of the vaccine. At this time, the FDA, NIH, and CDC are still studying the bowel obstruction and RotaShield-associated cases, Egan says. "We continue to look into mechanisms for any serious adverse events. We want to understand why they happen so that we can prevent them from occurring in the future."
The CDC's Vaccine Safety DataLink, which links computerized histories of vaccination to hospitalization records and other medical information for members of eight large managed care organizations, supplements the information in VAERS and permits more rigorous evaluation of possible safety concerns. For example, the system allows researchers to compare how often an adverse event occurs in people recently vaccinated with those not recently vaccinated, to evaluate the likelihood that the vaccine caused the adverse event.