Commissioner of Food and Drugs, Food and Drug Administration
U.S. Department of Health and Human Services
Vaccines play a critical role in protecting people of all ages from serious and sometimes deadly diseases. Because vaccines play such an important role in public health, vaccine safety is one of our highest priorities at the Food and Drug Administration (FDA). FDA begins its evaluation of vaccine safety before a vaccine is even studied in human clinical trials and continues the evaluation as long as a vaccine is on the market. Once clinical trials begin, and throughout the clinical trial process, physicians and other scientists at FDA’s Center for Biologics Evaluation and Research (CBER) carefully assess the emerging safety information as well as information on effectiveness. FDA may only license a vaccine after clinical studies demonstrate that it is safe and effective. After licensure, physicians and other experts at FDA/CBER continue to evaluate safety information from any post market clinical trials and from routine use of the vaccine.
FDA has many tools to continually evaluate the safety of vaccines. One of the ways we monitor for safety is through the Vaccine Adverse Event Report System, which is jointly managed by FDA and the Centers for Disease Control and Prevention (CDC). Anyone can report adverse events following vaccinations, and we encourage reporting because it helps us better understand and identify potential emerging safety issues. FDA also combines data mining of adverse event reports with clinical review of individual cases to detect new safety issues, which are known as “safety signals.” Such issues may trigger additional evaluation. FDA calls this a “life-cycle” approach to vaccine safety because monitoring continues as long as the vaccine remains on the market.
To further enhance the evaluation of vaccine safety signals, FDA now utilizes the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system, which is the vaccine safety component of the FDA’s Mini-Sentinel Program. PRISM is the largest vaccine safety surveillance system in the United States, with active observation of a representative subset of the general population. Because PRISM has access to historical information for over 100 million people, FDA is able to identify and analyze rare health outcomes that have previously been challenging to assess.
With PRISM, we have greatly advanced vaccine safety surveillance. For example, beginning in 2010, several epidemiological studies conducted outside the United States suggested that intussusception, a potentially life threatening intestinal condition, might be linked to use of U.S. licensed rotavirus vaccines. Such information led FDA to initiate the largest study of this issue in PRISM to quantify the potential risk of intussusception after administration of rotavirus vaccine among U.S. children. Less than three years later, the PRISM system reported conclusions from an analysis of more than 1.2 million RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) vaccinations among infants 5 through 36 weeks of age. The study identified an increased risk of intussusception 21 days following the first dose of RotaTeq, with the majority of cases occurring in the first 7 days. As a result, FDA required a safety labeling change in the Prescribing and Patient Information for RotaTeq. The label now describes important signs and symptoms of intussusception as well as the risk attributed to vaccine use. Safety data had previously indicated a risk of intussusception with use of another U.S. licensed rotavirus vaccine, Rotarix, leading to a similar labeling change. It is important to note that the risk of intussusception is small, and the benefits of these rotavirus vaccines continue to outweigh the risks.
FDA devotes considerable scientific expertise to monitoring and evaluating reports of potential adverse events following vaccination. Now, the PRISM system can significantly decrease the time between safety signal identification and evaluation. PRISM has also increased the precision of risk estimates, which better inform FDA in actions it may take to protect and promote the health of the American public.