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

• 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

Vaccines

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