Determining safe yet effective drug dosages for children is an ongoing challenge for pharmaceutical companies and doctors alike. A new drug is usually tested in adults first, and the results of these studies are used to select doses for pediatric studies. The underlying assumption is typically that children are like adults, only smaller, which is often true, but can also overlook differences that arise from the fact that children’s organs are still developing.
To compound the problem, pediatric studies don’t always shed light on other differences that can affect drug dose recommendations. There are many factors that limit children’s participation in drug trials – for example, some diseases are simply less common in children – and as a result, the data sets generated are typically very sparse.
In order to make medicines and their development safer for children, researchers from Aalto University in Finland and the pharmaceutical company Novartis have developed a method with which the available data can be better used.
“This is a method that can help determine safe drug doses faster and with fewer observations than before,” says co-author Aki Vehtari, Professor of Computer Science at Aalto University and the Finnish Center for Artificial Intelligence.
For the study, the research team created a model that enables a better understanding of the development of the organs.
“The size of an organ isn’t necessarily the only thing that affects its performance. Children’s organs are just not as efficient as those of adults. In drug modeling, if size is the only factor we may be delivering too many doses, ”explains Eero Siivola, lead author of the study and a PhD student at Aalto University.
While the standard approach to assessing pediatric data is based on subjective assessments of the model diagnostics, the new approach is more data-driven and consequently less prone to bias. It is also better to deal with small sample sizes as uncertainties are taken into account.
In the study, researchers are demonstrating their approach by re-examining a pediatric study examining everolimus, a drug used to prevent organ transplant rejection. However, the approach could be particularly useful in situations where a new drug is being tested on an entirely new group of children or adults who are small, potentially making the testing phase much more efficient than it is now. Another promising application is in extending the use of an existing drug to other symptoms or diseases; The method could support this process more effectively than current practices.
The paper will be published in the magazine on May 10th Statistics in Medicine, already available online.
Edited by Gary Cramer