FDA’s research guidance will help take guesswork out of drug dosing in newborns

When we need to give medicine to newborns in our hospital, we often have to guess at the correct dose to give them. That’s a problem: give too little and the medicine might not work; give too much and it might cause harm. Dosing newborn babies with greater precision has been a challenge because it is difficult to conduct studies in this population, many of whom are very small and often critically ill.

For researchers trying to determine the appropriate dosing for a medicine for adults, the FDA has clear guidelines on how to give the medicine, collect blood samples, examine the drug level in the blood, apply math to analyze how the level changes over time, and make decisions based on these analyses.

But these guidelines don’t necessarily work for studying drugs in full-term and premature babies, who could weigh as little as 1 pound. Not only are newborns smaller, but their organs aren’t yet fully developed, so it may take longer for them to process or excrete medicines compared to older children and adults. It is also harmful to take as many blood samples from a newborn as can be taken from an adult.

Over the past two decades, pediatric teams like ours at the Duke Clinical Research Institute (DCRI) have been working to create and apply new ways to study medicines to determine the correct dose for medications babies need. This work helped inform guidance published by the FDA in July on clinical pharmacological studies in neonates, which is a big step in the right direction.

Through our work at the DCRI and the work of the Pediatric Trials Network, a national organization that studies medication safety and effectiveness in children, methods have been developed to take smaller and fewer blood samples from newborns and use innovative mathematical analyses that better predict the correct dose and make it possible to enroll fewer babies per study. The use of opportunistic studies — studying drugs that are already being administered to infants and analyzing blood samples taken in the course of normal care — helps alleviate the burden on patients and their caregivers.

The FDA guidance addresses best practices for clinical trial design, medication dosing, and data analysis, among others. We hope that all organizations studying newborns, from industry sponsors to the NIH, will incorporate these recommendations into their work.

This guidance should just be the beginning of our research focus on newborns. For many diseases commonly found in these vulnerable individuals, we have yet to identify medicines that can prevent their devastating consequences. And we have only limited information on how medicines given to newborns affect long-term growth and brain development.

To ensure the safety and health of newborns for decades to come, researchers must continue their efforts to equip health care practitioners with much needed information to confidently prescribe safe and effective medicines.

Michael Cohen-Wolkowiez, M.D., is a professor of pediatrics at the Duke University School of Medicine. Kanecia Zimmerman, M.D., is an associate professor of pediatrics at Duke. Both are members of the Duke Clinical Research Institute.