Active surveillance of vaccine safety: a system to detect early signs of adverse events.
BACKGROUND
There currently are no population-based systems in the United States to rapidly detect adverse events after newly introduced vaccines. To evaluate the feasibility of developing such systems, we used 5 years of data from 4 health maintenance organizations within the Centers for Disease Control and Prevention (CDC) Vaccine Safety Datalink.


METHODS
Within every year, each week's vaccinated children were followed for 4 weeks, and rates of adverse events were compared with rates among children of similar ages before the introduction of the new vaccine. We assessed risks for intussusception after rotavirus vaccination and risks for fever, seizures, and other neurologic adverse events after the change from whole cell diphtheria-tetanus-pertussis (DTPw) to acellular DTP vaccine (DTPa). We used sequential probability ratio testing, adjusted for age, sex, calendar time, season, and HMO, and with a stopping value based on the probability of an adverse event under the null hypothesis and under a preset alternative hypothesis.


RESULTS
We detected an increase in intussusception after 2589 vaccine doses of rotavirus vaccine, about the same time initial reports of intussusception were made to the Vaccine Adverse Events Reporting System. Decreases in risk for fever, seizures, and other abnormal neurologic events became detectable within 12 weeks, 42 weeks, and 18 months, respectively, after the change from DTPw to DTPa.


CONCLUSIONS
We conclude that it is feasible to develop systems for rapid and routine population-based assessments of new vaccine safety.
Davis
Robert L
RL
Departments of Epidemiology and Pediatrics, University of Washington, Seattle, Washington, USA. rad2@cdc.gov
Kolczak
Margarette
M
Lewis
Edwin
E
Nordin
James
J
Goodman
Michael
M
Shay
David K
DK
Platt
Richard
R
Black
Steven
S
Shinefield
Henry
H
Chen
Robert T
RT
D016208:Databases, Factual; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects*; D005334:Fever / Q000139:chemically induced / Q000453:epidemiology; D006279:Health Maintenance Organizations / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D007443:Intussusception / Q000139:chemically induced / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D022243:Rotavirus Vaccines / Q000009:adverse effects*; D012621:Seasons; D014481:United States / Q000453:epidemiology
D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022243:Rotavirus Vaccines