title: Early detection of adverse drug events within population-based health networks: application of sequential testing methods.
abstract: OBJECTIVE
  Active surveillance of population-based health networks may improve the timeliness of detection of adverse drug events (ADEs). Active monitoring requires sequential analysis methods. Our objectives were to (1) evaluate the utility of automated healthcare claims data for near real-time drug adverse event surveillance and (2) identify key methodological issues related to the use of healthcare claims data for real-time drug safety surveillance.
  
  
  METHODS
  We assessed the ability to detect ADEs using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Analyses were performed using a maximized sequential probability ratio test (maxSPRT). Five drug-event pairs representing known associations with an ADE and two pairs representing 'negative controls' were analyzed.
  
  
  RESULTS
  Statistically significant (p < 0.05) signals of excess risk were found in four of the five drug-event pairs representing known associations; no signals were found for the negative controls. Signals were detected between 13 and 39 months after the start of surveillance. There was substantial variation in the number of exposed and expected events at signal detection.
  
  
  CONCLUSIONS
  Prospective, periodic evaluation of routinely collected data can provide population-based estimates of medication-related adverse event rates to support routine, timely post-marketing surveillance for selected ADEs.
authors.affiliation: Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, USA. jeff_brown@harvardpilgrim.org
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Brown
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
authors.forename: Robert L
authors.initials: RL
authors.lastname: Davis
authors.forename: David
authors.initials: D
authors.lastname: Graham
authors.forename: Parker T
authors.initials: PT
authors.lastname: Pettus
authors.forename: Susan E
authors.initials: SE
authors.lastname: Andrade
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Raebel
authors.forename: Lisa
authors.initials: L
authors.lastname: Herrinton
authors.forename: Douglas
authors.initials: D
authors.lastname: Roblin
authors.forename: Denise
authors.initials: D
authors.lastname: Boudreau
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Gurwitz
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000465:Algorithms; D000068579:Celecoxib; D016536:Competitive Medical Plans / Q000458:organization & administration / Q000706:statistics & numerical data; D006279:Health Maintenance Organizations / Q000458:organization & administration / Q000706:statistics & numerical data; D006801:Humans; D007345:Insurance Claim Review / Q000706:statistics & numerical data; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D016347:Medical Records Systems, Computerized / Q000706:statistics & numerical data; D009203:Myocardial Infarction / Q000139:chemically induced / Q000175:diagnosis; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D011159:Population Surveillance / Q000379:methods*; D011358:Product Surveillance, Postmarketing / Q000379:methods* / Q000706:statistics & numerical data; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000175:diagnosis; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D007783:Lactones; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; C086276:cerivastatin; D000068579:Celecoxib