title: A Synthesis of Current Surveillance Planning Methods for the Sequential Monitoring of Drug and Vaccine Adverse Effects Using Electronic Health Care Data.
abstract: BACKGROUND
  The large-scale assembly of electronic health care data combined with the use of sequential monitoring has made proactive postmarket drug- and vaccine-safety surveillance possible. Although sequential designs have been used extensively in randomized trials, less attention has been given to methods for applying them in observational electronic health care database settings.
  
  
  METHODS
  We review current sequential-surveillance planning methods from randomized trials, and the Vaccine Safety Datalink (VSD) and Mini-Sentinel Pilot projects-two national observational electronic health care database safety monitoring programs.
  Based on this examination, we suggest three steps for future surveillance planning in health care databases: (1) prespecify the sequential design and analysis plan, using available feasibility data to reduce assumptions and minimize later changes to initial plans; (2) assess existing drug or vaccine uptake, to determine if there is adequate information to proceed with surveillance, before conducting more resource-intensive planning; and (3) statistically evaluate and clearly communicate the sequential design with all those designing and interpreting the safety-surveillance results prior to implementation. Plans should also be flexible enough to accommodate dynamic and often unpredictable changes to the database information made by the health plans for administrative purposes.
  
  
  CONCLUSIONS
  This paper is intended to encourage dialogue about establishing a more systematic, scalable, and transparent sequential design-planning process for medical-product safety-surveillance systems utilizing observational electronic health care databases. Creating such a framework could yield improvements over existing practices, such as designs with increased power to assess serious adverse events.
authors.affiliation: Group Health Research Institute; University of Washington.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Nelson
authors.affiliation: Group Health Research Institute.
authors.forename: Robert
authors.initials: R
authors.lastname: Wellman
authors.affiliation: Group Health Research Institute.
authors.forename: Onchee
authors.initials: O
authors.lastname: Yu
authors.affiliation: Group Health Research Institute; University of Washington.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Cook
authors.affiliation: Harvard Medical School; Harvard Pilgrim Health Care Institute.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Maro
authors.affiliation: Food and Drug Administration.
authors.forename: Rita
authors.initials: R
authors.lastname: Ouellet-Hellstrom
authors.affiliation: Group Health Research Institute; University of Washington.
authors.forename: Denise
authors.initials: D
authors.lastname: Boudreau
authors.affiliation: University of Washington.
authors.forename: James S
authors.initials: JS
authors.lastname: Floyd
authors.affiliation: University of Washington.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Food and Drug Administration.
authors.forename: Simone
authors.initials: S
authors.lastname: Pinheiro
authors.affiliation: Food and Drug Administration.
authors.forename: Marsha
authors.initials: M
authors.lastname: Reichman
authors.affiliation: Food and Drug Administration.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Shoaibi
keywords: adverse drug reaction reporting systems; drug-related side effects and adverse reactions; electronic health records; product surveillance, postmarketing; sequential analysis; vaccine/adverse effects