title: Active surveillance for adverse events: the experience of the Vaccine Safety Datalink project.
abstract: OBJECTIVE
  To describe the Vaccine Safety Datalink (VSD) project's experience with population-based, active surveillance for vaccine safety and draw lessons that may be useful for similar efforts.
  
  
  METHODS
  The VSD comprises a population of 9.2 million people annually in 8 geographically diverse US health care organizations. Data on vaccinations and diagnoses are updated and extracted weekly. The safety of 5 vaccines was monitored, each with 5 to 7 prespecified outcomes. With sequential analytic methods, the number of cases of each outcome was compared with the number of cases observed in a comparison group or the number expected on the basis of background rates. If the test statistic exceeded a threshold, it was a signal of a possible vaccine-safety problem. Signals were investigated by using temporal scan statistics and analyses such as logistic regression.
  
  
  RESULTS
  Ten signals appeared over 3 years of surveillance: 1 signal was reported to external stakeholders and ultimately led to a change in national vaccination policy, and 9 signals were found to be spurious after rigorous internal investigation. Causes of spurious signals included imprecision in estimated background rates, changes in true incidence or coding over time, other confounding, inappropriate comparison groups, miscoding of outcomes in electronic medical records, and chance. In the absence of signals, estimates of adverse-event rates, relative risks, and attributable risks from up-to-date VSD data have provided rapid assessment of vaccine safety to policy-makers when concerns about a specific vaccine have arisen elsewhere.
  
  
  CONCLUSIONS
  Care with data quality, outcome definitions, comparison groups, and length of surveillance are required to enable detection of true safety problems while minimizing false signals. Some causes of false signals in the VSD system were preventable and have been corrected, whereas others will be unavoidable in any active surveillance system. Temporal scan statistics, analyses to control for confounding, and chart review are indispensable tools in signal investigation. The VSD's experience may inform new systems for active safety surveillance.
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 133 Brookline Ave, Boston, MA 02215, USA. katherine_yih@harvardpilgrim.org
authors.forename: W Katherine
authors.initials: WK
authors.lastname: Yih
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Fireman
authors.forename: Irene M
authors.initials: IM
authors.lastname: Shui
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Lewis
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: James
authors.initials: J
authors.lastname: Baggs
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weintraub
authors.forename: Edward A
authors.initials: EA
authors.lastname: Belongia
authors.forename: Allison
authors.initials: A
authors.lastname: Naleway
authors.forename: Julianne
authors.initials: J
authors.lastname: Gee
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Lieu
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003628:Database Management Systems; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D018570:Risk Assessment; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D014612:Vaccines