Paediatric safety signals identified in VigiBase: Methods and results from Uppsala Monitoring Centre

Pharmacoepidemiol Drug Saf. 2019 May;28(5):680-689. doi: 10.1002/pds.4734. Epub 2019 Feb 15.

Abstract

Purpose: The purpose of this study is to uncover previously unrecognised risks of medicines in paediatric pharmacovigilance reports and thereby advance a safer use of medicines in paediatrics.

Methods: Individual case safety reports (ICSRs) with ages less than 18 years were retrieved from VigiBase, the World Health Organization (WHO) global database of ICSRs, in September 2014. The reports were grouped according to the following age spans: 0 to 27 days; 28 days to 23 months; 2 to 11 years; and 12 to 17 years. vigiRank, a data-driven predictive model for emerging safety signals, was used to prioritise the list of drug events by age groups. The list was manually assessed, and potential signals were identified to undergo in-depth assessment to determine whether a signal should be communicated.

Results: A total of 472 drug-event pairs by paediatric age groups were the subject of an initial manual assessment. Twenty-seven drug events from the two older age groups were classified as potential signals. An in-depth assessment resulted in eight signals, of which one concerned harm in connection with off-label use of dextromethorphan and another with accidental overdose of olanzapine by young children, and the remaining signals referred to potentially new causal associations for atomoxetine (two signals), temozolamide, deferasirox, levetiracetam, and desloratadine that could be relevant also for adults.

Conclusions: Clinically relevant signals were uncovered in VigiBase by using vigiRank applied to paediatric age groups. Further refinement of the methodology is needed to identify signals in reports with ages under 2 years and to capture signals specific to the paediatric population as a risk group.

Keywords: adverse drug reaction reporting systems; individual case safety reports; paediatrics; pharmacoepidemiology; pharmacovigilance.

MeSH terms

  • Adolescent
  • Adverse Drug Reaction Reporting Systems* / organization & administration
  • Adverse Drug Reaction Reporting Systems* / statistics & numerical data
  • Age Factors
  • Child
  • Child, Preschool
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Humans
  • Infant
  • Product Surveillance, Postmarketing / methods*
  • Sweden
  • World Health Organization