title: Prospective influenza vaccine safety surveillance using fresh data in the Sentinel System.
abstract: To develop the infrastructure to conduct timely active surveillance for safety of influenza vaccines and other medical countermeasures in the Sentinel System (formerly the Mini-Sentinel Pilot), a Food and Drug Administration-sponsored national surveillance system that typically relies on data that are mature, settled, and updated quarterly.
  
  
  
  Three Data Partners provided their earliest available ("fresh") cumulative claims data on influenza vaccination and health outcomes 3-4 times on a staggered basis during the 2013-2014 influenza season, collectively producing 10 data updates. We monitored anaphylaxis in the entire population using a cohort design and seizures in children ≤4 years of age using both a self-controlled risk interval design (primary) and a cohort design (secondary). After each data update, we conducted sequential analysis for inactivated (IIV) and live (LAIV) influenza vaccines using the Maximized Sequential Probability Ratio Test, adjusting for data-lag.
  
  
  
  Most of the 10 sequential analyses were conducted within 6 weeks of the last care-date in the cumulative dataset. A total of 6 682 336 doses of IIV and 782 125 doses of LAIV were captured. The primary analyses did not identify any statistical signals following IIV or LAIV. In secondary analysis, the risk of seizures was higher following concomitant IIV and PCV13 than historically after IIV in 6- to 23-month-olds (relative risk = 2.7), which requires further investigation.
  
  
  
  The Sentinel System can implement a sequential analysis system that uses fresh data for medical product safety surveillance. Active surveillance using sequential analysis of fresh data holds promise for detecting clinically significant health risks early. Limitations of employing fresh data for surveillance include cost and the need for careful scrutiny of signals. © 2015 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Weiling Katherine
authors.initials: WK
authors.lastname: Yih
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Sukhminder K
authors.initials: SK
authors.lastname: Sandhu
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Zichittella
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Maro
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Cole
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Alison Tse
authors.initials: AT
authors.lastname: Kawai
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Meghan A
authors.initials: MA
authors.lastname: Baker
authors.affiliation: Government and Academic Research, HealthCore, Alexandria, VA, USA.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Aetna Data Science, Aetna, Blue Bell, PA, USA.
authors.forename: Cheryl N
authors.initials: CN
authors.lastname: McMahill-Walraven
authors.affiliation: Comprehensive Health Insights, Humana Inc., Louisville, KY, USA.
authors.forename: Mano S
authors.initials: MS
authors.lastname: Selvan
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nguyen
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000707:Anaphylaxis / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012640:Seizures / Q000453:epidemiology*; D018571:Sentinel Surveillance; D014481:United States; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated
keywords: epidemiologic monitoring; influenza vaccines; pharmacoepidemiology; postmarketing product surveillance; research design; sequential analysis; vaccine safety