Enhanced Paediatric Pharmacovigilance at the European Medicines Agency: A Novel Query Applied to Adverse Drug Reaction Reports.

Background: Databases of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance. With increasing numbers of reports, additional statistical approaches are needed to better use the data.

Aim: The present study was aimed at elucidating the European Medicines Agency's (EMA) use of a novel 'paediatric' query to analyse the data in its ADR database 'EudraVigilance'.

Methods: The proportional reporting ratio (PRR) is a measure of disproportionality for which the underlying principle is that a drug-event pair of interest is reported more often than expected relative to an independence model. The EMA's paediatric query, based on PRRs, was applied to the data in EudraVigilance to investigate the extent to which the known association between enalapril and renal toxicity was reflected in reported ADRs comparing children with adults and with adjustment for the effect of multiplicity.

Results: The comparison of PRRs for children (14.91, 95% confidence interval [CI] 13.05-17.04) versus adults (2.66, 95% CI 2.52-2.82) confirmed a higher risk of renal ADRs with enalapril when used in children compared with all other medicines and compared with adults.

Conclusions: The EMA's paediatric query can be used to highlight an imbalance for a drug-event pair among ADRs for a medicine when used in children and as compared with adults. Applying the query in practice can help the EMA to decide on whether stand-alone paediatric medicine development is warranted, and which, if any, further studies are necessary. Ongoing evaluation of the query is contributing to the development of new methods and guidance.