1. The Vaccine Adverse Event Reporting System: A Tool for Safety and Surveillance Jane Woo, MD, MPH Vaccine Safety Branch Division of Epidemiology Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research September 16, 2005

2. Highly effective and extremely safe A foundation of public health disease prevention programs Different from other pharmaceuticals in ways that influence safety considerations With diseases now controlled by vaccination and thus rarely observed, there is a greater focus on safety Vaccines

3. Administered to millions of children and adults every year Mandated for school entry Known to cause or contribute to a very small number of severe injuries Suspected by some to be responsible for a variety of health problems Vaccines

4. Temporal Associations Between Vaccinations and Serious Illnesses Cause Public Concern Autism Attention Deficit Disorder Brain Damage Sudden Infant Death Syndrome (SIDS) Cancer Asthma Diabetes Arthritis Multiple Sclerosis Inflammatory Bowel Disease

5. Problem: Coincidence or Cause? For products with widespread use, some serious medical events will occur coincidentally after administration Often impossible to ascertain likelihood of causal connection with vaccine

6. Example 4 million children born in US each year Infants receive 15+ immunizations on 4-5 occasions in the first 12 months of life About 1/1500 babies dies of SIDS in US each year By chance alone, 50-100 babies each year can be expected to die of SIDS within 2 days of vaccination

7. Vaccine Adverse Event Reporting System (VAERS) National system for passive surveillance Reports received from health professionals, vaccine manufacturers, and the public > 15,000 reports per year submitted Plausible connection of vaccine with serious events is rare

8. How can VAERS be used to monitor vaccine safety? Many clinical trials are not large enough to reveal rare adverse events Reports of serious events reviewed individually; reviewers look for patterns that could suggest plausible link of an event to a vaccine VAERS data may help generate hypotheses

9. Data Mining Methods Automated techniques that identify events reported more commonly for one product than others Proportional reporting ratios Empirical Bayesian methods An elevated numerical score may constitute a signal that should be further investigated FDA Guidance for Industry on Pharmacovigilance Planning provides guidelines on signal detection

10. Data Mining and VAERS To study adverse events after a particular vaccine, we can use recipients of other vaccines as quasi control group Intussusception after rotavirus vaccine Vaccine 19:4627-34, 2001 Adverse events after typhoid vaccines Clin Infect Dis 38:771-779, 2004 Photophobia after smallpox vaccine Vaccine 23:1097-1098, 2005

11. What are the limitations of VAERS? Uncertain denominator Underreporting and incomplete information Coincidental events inevitable Reporting rates influenced by media and other factors Can almost never disprove causal link between a vaccine and an adverse event

12. VAERS Surveillance: Accomplishments Overviews of VAERS reports for new vaccines –Hepatitis A –Varicella –Acellular Pertussis –Pneumococcal conjugate Evaluation of data mining techniques Identification of safety concerns –Serious thrombocytopenia –Alopecia –Administration of varicella vaccine instead of varicella immunoglobulin

13. Contributions to Public Health Reassure public that vaccines are safe; if we find nothing new or unexpected, we want the public to know Highlight any potential concerns and encourage further study Public awareness of continuous surveillance may enhance confidence in vaccine safety