Model informed drug development and precision dosing in neonates and infants (MONI)

Designing safe and effective medicines for children is a complex process. One major challenge is that clinical trials in children, especially newborn babies, infants and toddlers, are more limited than those in adults. This is due to a smaller numbers of patients, limited blood sampling for testing, and important ethical considerations.
As a result, doses for children are often selected based on how the drug works in adults or older children. However, this is not always reliable, because children’s bodies process drugs differently at different stages of development. For example, how the body removes a medicine—known as drug elimination—changes from birth through early childhood and into adulthood. These changes affect how much medicine a child needs to get the same effect as an adult.
To improve dose selection in children, researchers use computer-based tools involving modelling and simulation. These tools allow us to estimate how drugs behave in children’s bodies, by taking into account factors like body size. But for children under two years of age, adjusting for body size alone is not enough. Other factors, such as the developmental changes in drug-specific elimination processes with age must also be considered.
There are many different methods used in the scientific literature to estimate how children eliminate drugs, but no clear strategy has been established. Another important issue is designing studies: e.g. how many children to include in a study, and how many samples to collect from each child. This is important to estimate precisely factors influencing dose selection, while avoiding unnecessary tests in young patients.
Our goal is to evaluate and improve existing tools that help predict how drugs are cleared from the bodies of children under two years old. We will focus on a previously developed method using decision tables based on a child’s age and the drug’s characteristics, while integrating designing studies to guide dose prediction.
We will:
1. Test the precision of different methods to predict how drugs are cleared from the body in young children. These methods will include different ways of adjusting for body size and development.
2. Compare study design strategies to find the best approach for collecting the right amount of data—balancing scientific needs with the goal of minimizing the burden on young patients. This research will help create a basis for more reliable guidelines for determining the right drug doses in very young children and support better clinical trial design.