The Vaccine Adverse Event Reporting System A Tool

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

Vaccines • 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 • 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

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

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

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

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

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

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

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

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

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

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