Substantial Delays in Postapproval Pediatric Testing for New Drugs

A recent review of new drugs approved between 2015 and 2021 showed that testing these drugs on children, as required by the Pediatric Research Equity Act (PREA), is often delayed.¹

According to a research letter published in JAMA, more than half of these required studies remain incomplete, even years after the drugs were approved for use. This delay raises concerns about how quickly important safety and effectiveness information becomes available for children, who are often left out of early drug testing.

PREA was passed in 2003 with the goal of closing the gap in pediatric drug testing by requiring clinical trials for new drugs to include children, with certain exemptions for rare diseases and conditions not affecting children.² However, despite this legislative effort, a study examining 323 new drugs approved during this 6-year period found that only 30% were subject to pediatric testing requirements.¹ Even among those, most trials were delayed.

PREA was passed in 2003, aiming to close the gap in pediatric drug testing | Image credit: VadimGuzhva – stock.adobe.com

The prevalence of rare disease designations played a key role in limiting the scope of PREA, as nearly half (46%) of the 323 drugs approved during the study period were designated for rare diseases, exempting them from pediatric testing requirements. Of the exempt drugs, 38% did not have pediatric testing requirements because of its designation, and 22% of the drugs had pediatric testing waived due to impracticality. Only 10% met all pediatric testing requirements at the time of approval. The rest (30%) were assigned to 256 FDA-mandated pediatric studies.

Of the 256 required studies for 97 of the drugs approved between 2015 and 2021, only 28% of these trials had been completed by May 2024. In comparison, for drugs approved between 2007 and 2014, only one-third of postmarketing studies were completed in the following 6.8 years.³

Another 17% of the 256 trials had been released by the FDA without completion, while 53% were still ongoing.¹ Many trials are not being completed within their initially projected timelines, as 55 (41%) of the 135 ongoing trials had already passed their initial deadlines. The median time from drug approval to projected trial completion was 5.51 years, with a 3-year median trial completion deferral.

As noted by the authors, these findings reflect the growing trend of rare disease drug approvals, which has limited the overall impact of PREA. The number of drugs with rare disease designations has increased from 15% of new approvals between 1999 and 2003 to nearly half of all approvals from 2015 to 2021. This surge in rare disease drug approvals, while promising for patients with unmet medical needs, has further narrowed the scope of PREA’s reach.

According to the authors, further reforms may be necessary to ensure that postapproval pediatric testing obligations are met within reasonable timelines.

“In 2024, Congressional legislators introduced the Innovation in Pediatric Drugs Act, which would eliminate the rare disease exemption from mandatory pediatric testing under PREA,” the authors noted. “This study suggests that elimination of the rare disease exemption may increase pediatric testing requirements for new drugs, although additional reforms may be necessary.”

References

1. Liu ITT, Hwang TJ, Kesselheim AS. Testing of new drugs approved from 2015 through 2021 under the US Pediatric Research Equity Act. JAMA. Published online October 7, 2024. doi:10.1001/jama.2024.18338

2. Pediatric Research Equity Act of 2003, S 650, 108th Cong (2003)

3. Hwang TJ, Orenstein L, Kesselheim AS, Bourgeois FT. Completion rate and reporting of mandatory pediatric postmarketing studies under the US Pediatric Research Equity Act. JAMA Pediatr. 2019;173(1):68-74. doi:10.1001/jamapediatrics.2018.3416