National strategies to optimise dosing recommendations for children and their importance in Switzerland

For ethical and technical reasons, clinical studies only involved adults in the past and, therefore, data for safe and efficient drug use in children is lacking. In the absence of official dosing recommendations on drug labels, healthcare professionals need help prescribing the optimal dose for their paediatric patients. This thesis presents national strategies for the provision and optimisation of off-label dosing recommendations for children.
To assess the lack of dosing recommendations for children on Swiss drug labels, a systemic analysis was performed by quantifying the number of drugs not authorised for paediatric use. The introduction of new legislation enabled a database to be developed to fill this gap with nationally harmonised off-label dosing recommendations for children, based on evidence from the scientific literature combined with expert knowledge from clinical practice. When insufficient data were available to harmonise dosing recommendations, data from clinical routines were gathered from several Swiss children’s hospitals. An online platform was built to access and use these data for pharmacokinetic (PK) modelling, incorporating results of therapeutic drug monitoring (TDM) and pharmacogenetic (PGx) testing to optimise paediatric drug therapy.
45% of all drugs available in Switzerland are not authorised for use in children, and consequently off-label prescribing is widespread in paediatric care. A standardised harmonisation process was established and to date 643 off-label dosing recommendations for 202 active substances were published in the SwissPedDose database. When harmonisation was challenging, dosing recommendations were optimised by applying PK modelling based on health-related personal data and plasma drug concentrations using the recently developed online platform SwissPKcdw. It enabled a PGx analysis of voriconazole treatment in children, revealing that genetic variants within drug metabolising enzymes and drug transporters affected voriconazole trough concentrations.
Since Swiss drug labels lack paediatric dosing recommendations, more emphasis should be placed on improving the safety of off-label prescribing for children. The national harmonisation of off-label dosing recommendations and the collection of real-world data from multiple hospitals in order to apply PK modelling are important strategies that allow optimal dosing recommendations to be achieved for children.