The impact of legislation on drug substances used off-label in paediatric wards--a nationwide study

Abstract

Purpose: This nationwide study is aimed at describing to what extent the European Paediatric Regulation has met therapeutic needs in children.

Methods: Data for each drug substance in defined daily doses (DDD) were extracted from the national Danish data base. We evaluated if drug substances were used off-label and whether they had a paediatric investigation plan (PIP). This study did not include drug prescriptions for individual paediatric patients; thus, it was not possible to make use of all off-label categories previously used. Additionally, paediatric standard assortments (SA) were compared to the European survey on paediatric medicinal products.

Results: Thirteen percent of the 100 most used drug substances were determined as being used off-label, four of which had a PIP and one had a full waiver. Only one of the three drug substances used off-label most often, accounting for 85 % of such use, had a PIP. Neonates were included in one-third of PIPs and adolescents in 15. Nineteen out of 21 PIPs had a waiver and 14 PIPs were deferred. In line with the European survey, carbapenems, corticosteroids and proton pump inhibitors were frequent found in SAs.

Conclusion: PIPs only cover a small proportion of the drugs found to be used off-label in this study. Despite waivers granted, drug substances were used nonetheless. Unmet regulatory needs are still considerable in some therapeutic areas in neonates as well as in children.