Key Points:
- A novel algorithm can identify 20,000 drug side effects across seven pediatric development stages.
- Taking age/development into account, the method provides more accurate prescribing guidelines for pediatric clinicians.
- Currently, side effects from pediatric drug treatment are responsible for nearly 10 percent of childhood hospitalizations, with nearly half of those being life-threatening.
Clinical trials are the gold standard for identifying adverse drug events (ADEs) for adults but, for a multitude of reasons, children are generally not included in these trials. This forces doctors to prescribe medication to children off-label, essentially treating them as “mini-adults,” which can be dangerous.
Now, researchers at Columbia University Irving Medical Center have used predictive modeling on real-world data to address the critical gap in healthcare research surrounding pediatric patients. The team developed a novel algorithm that identified nearly 20,000 ADEs signals—information on a new or known side effect that may be caused by a drug—across the seven pediatric development stages.
The main innovation is the focus on ADEs across seven developmental stages, starting at neonatal and going through late adolescence. Previously, children 18 and younger were grouped together, with no caveats for the difference between a 2-year-old and a 16-year-old.
The algorithm also allows the sharing of information from “neighboring” stages. For example, the development of infants and toddlers is close enough that there will be more shared characteristics than there would be for infants and those in early or late adolescence.
Researcher Nick Giangreco, a recent systems biology Ph.D. graduate at Columbia University, noted the success the model had with montelukast, an asthma drug.
“We corroborated what the FDA had found—that montelukast was found to elicit psychiatric side effects,” he said. “We saw that in our database as well, but we were able to pinpoint certain developmental stages where the risk was more significant, especially the second year of life.”
This and the rest of the data from the study is available via KidSIDES, a free and publicly available database of pediatric drug safety signals for the research community, as well as the Pediatric Drug Safety portal (PDSportal), which will facilitate evaluation of drug safety signals across childhood growth and development.
“The primary intention is for other researchers to use it, to follow up on signals they may observe,” said associate professor Nicholas Tatonetti. “If they are experts on a particular drug usage, or particular disease domain and have observed these types of effects, they could follow up on them and be reassured, or could look at what the other evidence is for that effect as we aggregate it together. Clinicians can use it as a gut check. Maybe they saw an effect, or they are wondering if others are seeing this effect, and they can check the PDSPortal to see if others are seeing this effect or to prompt them to write another case report to the FDA.”
Information provided by Columbia University Irving Medical Center.