WASHINGTON, DC—Clinical trials may not be the way to go in assessing pediatric patients with rare diseases, a speaker said today at a session during the National Organization for Rare Disorders’ Rare Disease and Orphan Products Breakthrough Summit.

The session, which was moderated by James Baumberger, MPP, senior director of federal advocacy at the American Academy of Pediatrics, explored the demand for pediatric drug and medical device labeling.

Baumberger said children are not just little adults, and instead have unique physiology, grow, and develop and, as a result, have unique needs.

“Diseases present differently in kids, and all this means that we need therapies that are developed specifically with kids in mind,” he said. “We know that it’s an unfortunate reality that drug and device development is too often focused on adults, and that means that therapies for kids often go undeveloped or therapies are developed and then not appropriately studied in kids.”

Baumberger said the Best Pharmaceuticals for Children Act (BPCA) is an incentive for drug companies to conduct studies in kids, and a number of orphan drugs have been studied under BPCA. The Pediatric Research Equity Act (PREA) places a requirement on companies to do certain pediatric studies, but largely does not apply to orphan drugs.

Although the Pediatric Medical Device Safety and Improvement Act is in effect, Baumberger said more work is needed on device development.

Mona Khurana, MD, pediatric team leader of the US Food and Drug Administration’s Center for Drug Evaluation and Research (CDER), noted that although there have been significant advances in pediatric drug development, more needs to be done to develop therapies for rare pediatric diseases. 

“Together, BPCA and PREA have led to a substantial increase in the number of drugs and biologics approved with pediatric use information and labeling that was based on studies conducted in the pediatric population,” she continued.

However, Kurana noted that many of the successes are largely driven by completed pediatric studies that were required under PREA rather than studies that were incentivized under BPCA. Rare orphan diseases in pediatric patients are not captured with PREA-driven label changes, because orphan indications, except for some pediatric oncology indications, are not subject to PREA study requirements.

Vasum Peiris, MD, chief medical officer and director of pediatrics and special populations at the FDA, said health equity is a major issue when it comes to pediatric device development.

“We want to ensure that medical products, when they are being utilized in children, that they have the same benefit-risk profiles or at least the physicians that are using those profiles have the same benefit-risk information so that they can make informed decisions about the safety and potential help that these medical products can provide to children,” he said.

“Many times in the pediatric world, physicians have to use medical products in a physician-directed manner because there may not be a specific labeling indication.”

He also said that labeled pediatric drugs are growing at a rate 3 times greater than that of pediatric devices, giving a clear indication that more work still needs to be done.

Jerry Vockley, MD, PhD, chief of genetic and genomic medicine at UPMC Children’s Hospital of Pittsburgh in Pennsylvania, said research in pediatric patients with rare diseases is often put off until adulthood. He said that in rare diseases, damage is cumulative, so waiting until adulthood to do research may just mean more risk and less benefit.

He noted that in this patient population, a double-blind placebo-controlled trial often isn’t possible, so it might not be the most efficient endpoint.

“We are reaching an inflection point where it may well be in pediatric rare disease, the double-blind placebo-controlled trials may not be the gold standard anymore,” Vockley concluded. “The problem is there may not be a gold standard.”


Pediatric clinical trials and labeling. Presented at: National Organization for Rare Disorders’ Rare Disease and Orphan Products Breakthrough Summit; October 18, 2022; Washington, DC.