title: Patterns of spontaneous reports on narcolepsy following administration of pandemic influenza vaccine; a case series of individual case safety reports in Eudravigilance.
abstract: This study aims to describe the frequency and quality of spontaneous narcolepsy case reports following administration of pandemic influenza vaccine as captured in the Eudravigilance database.
  
  
  
  We conducted a retrospective descriptive study of spontaneous Individual Case Safety Reports (ICSRs), reporting narcolepsy following administration of pandemic influenza vaccine as received by Eudravigilance until July 2014. De-duplication was carried out by Eudravigilance. Frequency of reporting is described as number of ICSRs received per month over time. The quality of the ICSRs was evaluated by completeness of information and diagnostic certainty using the Automated Brighton Collaboration case definition tool (ABC-tool) for narcolepsy.
  
  
  
  After de-duplication, a total of 1333 ICSRs of narcolepsy and/or cataplexy following pandemic influenza vaccine were identified, originating from 18 countries worldwide. Most of the ICSRs (61.9%) originated from the signaling countries, Sweden and Finland. Although de-duplication of case reports was carried out, it is suspected that many duplicates exist, in particular from Sweden. The majority of the ICSRs (95.3%), reported exposure to Pandemrix®. Only few reports were received for Arepanrix® (1.6%) or Focetria® (0.5%), and Celvapan® (0.1%). Of those ICSRs reporting age, 73.1% concerned persons below age of 20years. When using the ABC-tool, all ICSRs were classified as having insufficient information to meet the Brighton Collaboration case definition of narcolepsy.
  
  
  
  An increase in reporting of narcolepsy appeared in Eudravigilance only after awareness was raised by the national authorities. Most narcolepsy reports were received from countries where the signal initially occurred, and were related to Pandemrix® in children/adolescents. Basic information about the patient and the exposure was present in most of the ICSRs. The ICSRs captured by Eudravigilance however, do not collect enough information to assess the diagnostic certainty according to the Brighton Collaboration case definition.
authors: Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands; Medicines Evaluation Board, Utrecht (CBG-MEB), The Netherlands. Electronic address: k.gadroen@erasmusmc.nl.
authors: Kartini
authors: K
authors: Gadroen
authors: Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands; Medicines Evaluation Board, Utrecht (CBG-MEB), The Netherlands.
authors: Sabine M J M
authors: SMJM
authors: Straus
authors: Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands; Medicines Evaluation Board, Utrecht (CBG-MEB), The Netherlands.
authors: Alexandra
authors: A
authors: Pacurariu
authors: Medicines Evaluation Board, Utrecht (CBG-MEB), The Netherlands.
authors: Daniel
authors: D
authors: Weibel
authors: European Medicines Agency (EMA), London, United Kingdom.
authors: Xavier
authors: X
authors: Kurz
authors: Medicines Evaluation Board, Utrecht (CBG-MEB), The Netherlands.
authors: Miriam C J M
authors: MCJM
authors: Sturkenboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005387:Finland; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000209:etiology*; D009426:Netherlands; D060735:Pharmacovigilance; D013548:Sweden; D006113:United Kingdom; D014611:Vaccination / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; C568072:arepanrix; C558220:focetria; C556153:pandemrix
keywords: Brighton Collaboration; Eudravigilance; H1N1; Narcolepsy; Pandemic influenza vaccine; Signal detection