PM.20.035 – MINNIE Model-INformed dosiNg in chIldrEn: best pharmacotherapy for every child

Route: Personalised medicine: the individual at the centre

Cluster question: 101 Can we model the human body and use smart technologies for health, nutritional, and toxicity research, drastically reducing the use of laboratory animals at the same time?

Even today, approximately 50% of all drugs prescribed to children are off-label. Pediatric efficacy and safety data are lacking to support their use. Linear extrapolation from adult doses to children has resulted in drug toxicity and therapeutic failure, sometimes even with fatal outcomes. Children are not small adults and this also applies to drug dosing in children. Growth and development can significantly impact the processes involved in the disposition and effect of drugs. As our understanding of the impact of growth and development on these biological processes increases, we can use this knowledge to model drug disposition and effect in children and predict the most optimal dose (bottom-up modeling and simulation or M&S approach). At the same time, drug disposition and effect data collected in children can also be used to inform optimal dosing using a top down M&S approach. An important strength of these modelling approaches is the possibility to quantify the impact of co-variates like age and disease severity on dosing requirements and thereby further personalize dosing based on patient characteristics. These M&S approaches are increasingly used and supported by the regulators to inform on doses during pediatric drug development. M&S is also used to describe disposition of marketed drugs. However, a structured approach to use M&S for wide-scale implementation of model-informed doses in clinical practice is missing. In this project, we aim to develop a framework to prioritize marketed drugs prescribed to children in need of model-informed doses, to use innovative M&S approaches to develop personalized dosing guidelines, to organize training and workshops to raise the awareness of the utility and state-of-the-art of M&S among pediatric health care providers and to implement these guidelines internationally in real-life clinical care. These efforts will ultimately result in optimize efficacy and safety of pediatric pharmacotherapy in each individual child.

Keywords

efficacy, implementation, modeling and simulation, pediatrics, pharmacodynamics, pharmacokinetics, Pharmacology, Safety

Other organisations

Leiden University (LEI)

Submitter

Organisation Radboudumc (RUMC)
Name Prof dr. Saskia N. de Wildt
E-mail saskia.dewildt@radboudumc.nl
Website https://www.radboudumc.nl/en/people/saskia-de-wildt