title: Speaking the same language? International variations in the safety information accompanying top-selling prescription drugs.
abstract: BACKGROUND
  The official prescribing information document distributed with a prescription drug is a key source of safety information, but it may include excessive or insufficient details.
  
  
  OBJECTIVE
  To compare prescribing information approved by the US Food and Drug Administration with the UK, Canada and Australia to identify content differences in safety warnings.
  
  
  METHODS
  For 20 top-selling prescription drugs, we used an automated natural language processing tool to calculate the number and severity of reported adverse drug reactions (ADRs). We fit hierarchical Poisson models and included fixed effects for other prescribing information characteristics. Separately, we analysed the appearance and content of 'black box' warnings.
  
  
  RESULTS
  There was substantial variation in safety content of approved prescribing information. Canada had the highest median ADRs per drug (138 (IQR 86-234)) and the UK had the lowest (84 (IQR 51-111)). The number of ADRs reported was on average 50% higher in Canada compared with the USA (ratio of ADRs/document: 1.5, 95% CI 1.4 to 1.6, p<0.001). By contrast, there were on average 15% fewer ADRs listed in the UK compared with the USA (ratio of ADRs/document 0.85 (95% CI 0.78 to 0.93, p<0.001), and 21% fewer ADRs listed in Australia compared with the USS (ratio of ADRs/document 0.79, 95% CI 0.74 to 0.85, p<0.001). There were no variations in ADR severity. The presence and qualitative content of boxed warnings also showed substantial diversity.
  
  
  CONCLUSIONS
  International variations exist in the presentation of safety data in drug prescribing information, which may have important implications for patient safety. Better international coordination is necessary to enhance use of this information for patient decision-making.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA. akesselheim@partners.org
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Franklin
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Jon D
authors.initials: JD
authors.lastname: Duke
mesh_terms: D003257:Consumer Product Safety; D019049:Developed Countries; D004348:Drug Labeling / Q000592:standards*; D006801:Humans; D009323:Natural Language Processing; D016012:Poisson Distribution; D055553:Prescription Drugs
chemical_list: D055553:Prescription Drugs
keywords: Adverse events, epidemiology and detection; Communication; Health policy; Information technology; Medication safety