No population left behind: Improving paediatric drug safety using informatics and systems biology

Abstract

Adverse drugs effects (ADEs) in children are common and may result in disability and death. The current paediatric drug safety landscape, including clinical trials, is limited as it rarely includes children and relies on extrapolation from adults. Children are not small adults but go through an evolutionarily conserved and physiologically dynamic process of growth and maturation. Novel quantitative approaches, integrating observations from clinical trials and drug safety databases with dynamic mechanisms, can be used to systematically identify ADEs unique to childhood. In this perspective, we discuss three critical research directions using systems biology methodologies and novel informatics to improve paediatric drug safety, namely child versus adult drug safety profiles, age-dependent drug toxicities and genetic susceptibility of ADEs across childhood. We argue that a data-driven framework that leverages observational data, biomedical knowledge and systems biology modelling will reveal previously unknown mechanisms of pediatric adverse drug events and lead to improved paediatric drug safety.