Most high-risk pediatric device approvals based on adult data

Fifteen of the 25 high-risk devices approved by the FDA between 2008 and 2011 for use in children were cardiovascular therapeutics, with approval for 22 of the 25 devices based on studies that enrolled patients 18 years and older, according to a study published online April 14 in Pediatrics.

The FDA considers a device such as an implantable pacemaker or a replacement valve as high risk, or class III, because it supports or sustains life. High-risk devices often are approved through a premarket approval (PMA) process that typically requires a pivotal clinical trial or through a humanitarian device exemption (HDE).

Most devices are studied in adult populations, with use in children often off-label. In 2007, Congress passed the Pediatric Medical Device Safety and Improvement Act to stimulate device innovation for pediatric patients.

Florence T. Bourgeois, MD, MPH, senior author and an emergency medicine physician at Boston Children’s Hospital, and colleagues evaluated trial evidence in pediatric device approvals following passage of the legislation. They reviewed FDA databases and reports that included PMA and HDE approvals between 2008 and 2011 to identify approvals for patients 21 years and younger, which is the age group the FDA defines as pediatric. Additionally, they looked at approvals specifically for patients 18 and younger, the age group most physicians consider pediatric.

They found 22 devices approved through the PMA process and three through the HDE program. Of the 25, 22 were approved for patients 18 and older and three for patients younger than 18. Cardiovascular therapeutics accounted for 60 percent of the approved devices.  

Only 4 percent of patients in the pivotal trials were 18 or younger and 21 devices weren’t studied in patients younger than 18. Eleven pivotal trials did not enroll patients younger than 21. Many of the trials were nonrandomized, open-label design with surrogate endpoints.  

Nineteen approvals required postmarketing studies. Three specified inclusion of pediatric patients, and the FDA reported all three as making “inadequate progress” as of September 2013.

“Our results suggest that most of the recent pediatric device development activity has been by manufacturers who have developed devices primarily for adults,” the researchers wrote. “They have obtained pediatric approval on the basis of study in a small age range of patients not typically considered pediatric (18–21 years), and the majority of sponsors assessed their products exclusively in adults.”

The landscape may change, though. The 2007 legislation included incentives for developing nonprofit consortiums. The establishment of those may spur more pediatric device approvals, Bourgeois and colleagues noted.

The FDA also has issued guidance and a final rule in 2013 to standardize pediatric data submitted from manufacturers that may inform future device development. In addition, the agency can now require follow-up beyond three years in pediatric device postmarketing studies.