title: Evaluation of serious adverse drug reactions: a proactive pharmacovigilance program (RADAR) vs safety activities conducted by the Food and Drug Administration and pharmaceutical manufacturers.
abstract: BACKGROUND
  The Food and Drug Administration (FDA) and pharmaceutical manufacturers conduct most postmarketing pharmaceutical safety investigations. These efforts are frequently based on data mining of databases. In 1998, investigators initiated the Research on Adverse Drug events And Reports (RADAR) project to investigate reports of serious adverse drug reactions (ADRs) and prospectively obtain information on these cases. We compare safety efforts for evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs the RADAR project.
  
  
  METHODS
  We evaluated the completeness of serious ADR descriptions in the FDA and RADAR databases and the comprehensiveness of notifications disseminated by pharmaceutical manufacturers and the RADAR investigators. A serious ADR was defined as an event that led to death or required intensive therapies to reverse.
  
  
  RESULTS
  The RADAR investigators evaluated 16 serious ADRs. Compared with descriptions of these ADRs in FDA databases (2296 reports), reports in RADAR databases (472 reports) had a 2-fold higher rate of including information on history and physical examination (92% vs 45%; P<.001) and a 9-fold higher rate of including basic science findings (34% vs 4%; P = .08). Safety notifications were disseminated earlier by pharmaceutical suppliers (2 vs 4 years after approval, respectively), although notifications were less likely to include information on incidence (46% vs 93%; P = .02), outcomes (8% vs 100%; P<.001), treatment or prophylaxis (25% vs 93%; P<.001), or references (8% vs 80%; P<.001).
  
  
  CONCLUSIONS
  Proactive safety efforts conducted by the RADAR investigators are more comprehensive than those conducted by the FDA and pharmaceutical manufacturers, but dissemination of related safety notifications is less timely.
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. cbenne@northwestern.edu
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Nebeker
authors.forename: Paul R
authors.initials: PR
authors.lastname: Yarnold
authors.forename: Cara C
authors.initials: CC
authors.lastname: Tigue
authors.forename: David A
authors.initials: DA
authors.lastname: Dorr
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.forename: John F
authors.initials: JF
authors.lastname: Hurdle
authors.forename: Dennis P
authors.initials: DP
authors.lastname: West
authors.forename: Denys T
authors.initials: DT
authors.lastname: Lau
authors.forename: Cara
authors.initials: C
authors.lastname: Angelotta
authors.forename: Sigmund A
authors.initials: SA
authors.lastname: Weitzman
authors.forename: Steven M
authors.initials: SM
authors.lastname: Belknap
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Andrew
authors.initials: A
authors.lastname: Evens
authors.forename: Steven M
authors.initials: SM
authors.lastname: Trifilio
authors.forename: D Mark
authors.initials: DM
authors.lastname: Courtney
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
mesh_terms: D016208:Databases, Factual; D004345:Drug Industry; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D033181:Information Dissemination; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D011446:Prospective Studies; D014481:United States; D014486:United States Food and Drug Administration