title: Comparison between paediatric and adult suspected adverse drug reactions reported to the European medicines agency: implications for pharmacovigilance.
abstract: BACKGROUND
  Databases systematically collecting reports of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance in that they provide on-going large-scale surveillance in the 'real-world' setting. Several studies have provided data on ADRs in children reported to national databases. EudraVigilance (EV) is the European Medicines Agency's (EMA) web-based system for reporting and evaluating suspected ADRs. Due to requirements on pharmaceutical companies to report ADRs that originate both inside and outside Europe, the data in EudraVigilance are global in nature. As such, it is potentially a rich source of information for paediatric pharmacovigilance.
  
  
  OBJECTIVE
  The present study sought to provide a descriptive overview comparing ADRs involving children and adolescents aged less than 18 years with those involving adults reported to EudraVigilance across national boundaries. The results will serve as a baseline to explore whether lessons can be learned for paediatric pharmacovigilance.
  
  
  METHODS
  All ADR reports received in EudraVigilance up to 13 June 2013 were analysed for overall numbers, age, gender, and geographic origin. Accurate age was determined when reported in valid format or calculated from the interval between date of birth and the reaction start date. The nature of the ADRs and the most frequently reported drug substances and drug event combinations were evaluated using Medical Dictionary for Regulatory Activities (MedDRA) 'preferred terms' (PTs) and 'system organ classes' (SOCs). The distribution over time of reported paediatric ADRs was also analysed.
  
  
  RESULTS
  As of 13 June 2013, EudraVigilance contained 3,291,593 spontaneous reports, for 75.9 % of which accurate age was determined; 11.2 % of these were paediatric reports. Paediatric ADRs were more common than those in adults under the MedDRA SOCs 'general and administration site', 'nervous system', 'skin and subcutaneous' and 'infections and infestations'. For children, the three most frequently reported MedDRA PTs, i.e. pyrexia, vomiting and convulsion (13, 6 and 4 % of reports, respectively), accounted for a greater proportion of reports than the corresponding top three in adults, i.e. nausea, dyspnoea and pyrexia (4, 4 and 3 % of reports, respectively). The 20 most reported active substances (12 of which are vaccines) together accounted for 52 % of paediatric reports as compared with 28 % of adult reports.
  
  
  CONCLUSIONS
  The present study applied a first-time approach to one of the largest databases worldwide of reported ADRs. It confirmed that reports of reactions in children were different to those in adults, not only in terms of reactions and drugs involved but also more concentrated around limited sets of reaction types and drugs. The possible causal association between a medicine or vaccine and the suspected ADR was not formally assessed in this study since the study analysed the characteristics of reported ADRs that were suspected and therefore not proven. However, the findings may help to identify pharmacovigilance activities that should be strengthened to reduce the burden of ADRs in children.
authors.affiliation: European Medicines Agency, 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK, kevin.blake@ema.europa.eu.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Blake
authors.forename: Cosimo
authors.initials: C
authors.lastname: Zaccaria
authors.forename: Francois
authors.initials: F
authors.lastname: Domergue
authors.forename: Edith
authors.initials: E
authors.lastname: La Mache
authors.forename: Agnes
authors.initials: A
authors.lastname: Saint-Raymond
authors.forename: Ana
authors.initials: A
authors.lastname: Hidalgo-Simon
mesh_terms: D000328:Adult; D002648:Child; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005060:Europe; D006801:Humans; D060735:Pharmacovigilance