Study: Most new drugs subject to PREA requirements have ongoing postmarketing studies

Of the 30% of new drugs approved between 2015 and 2021 with pediatric trial requirements under the Pediatric Research Equity Act (PREA), 53% had ongoing studies at median 5.6 years of follow-up, according to a recent research letter published in JAMA.

The results show an increase in the percentage of drugs subject to PREA requirements having ongoing studies, researchers said. Citing data from another study published in 2019 that looked at rates of completion of PREA requirements of drugs approved between 2007 and 2014, they noted that 34% of postmarketing studies had ongoing studies at median 6.8 years of follow-up.

“Studies have shown that waivers and deferrals of PREA requirements are common, while postapproval pediatric testing is often delayed,” Ian Liu, of the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital in Boston, and colleagues wrote in their paper.

Exclusivity extensions for written request studies required under PREA were a central concern of industry stakeholders responding to the US Food and Drug Administration’s (FDA) draft guidance on pediatric drug development, with commenters noting the agency’s intent to be more selective in awarding six-month exclusivity extensions for written request studies could decrease the number of pediatric studies and written requests for pediatric indications. (RELATED: Dual draft guidances outline FDA vision for pediatric drug development, exclusivity, Regulatory Focus 19 May 2023; Commenters push back on FDA’s plans for PREA compliance, pediatric exclusivity, Regulatory Focus 19 July 2023)

In their analysis, Liu and colleagues identified 323 new drugs approved by FDA between 2015 and 2021, evaluating which drugs had pediatric indications, pediatric study requirements, and the status of the study requirements. They found 86 drugs (27%) carried pediatric indications and 237 drugs (73%) were approved for use in adults, with 150 drugs (46%) overall having rare disease designations that exempted them from PREA study requirements.

Concerning drugs with pediatric indications, 124 drugs (38%) were exempted from pediatric testing requirements because of a rare disease designation, 70 drugs (22%) had their testing requirements waived, 32 drugs (10%) were initially approved with all their testing requirements completed, and 97 drugs (30%) had 256 mandated pediatric studies after approval.

When they analyzed the pediatric postmarketing requirements at a median of 5.6 years, the researchers found 71 requirements (28%) had been completed, 44 requirements (17%) had not been completed and been released by FDA, and 135 requirements (53%) were ongoing, and 6 requirements (2%) had a miscellaneous status. For the drugs with ongoing pediatric postmarketing requirements, there was a median of 5.51 years from approval to completion of trials as projected by FDA. Of the trials for ongoing pediatric requirements, 55 trials (41%) were delayed from their initial deadline with a median of 0.71 years before original projected trial completion. There were 49 requirements that had deferred deadlines, and these had a delay in their completion date of a median 3.0 years.

Liu and colleagues attributed the number of rare disease-designated drugs, which have increased from 15% between 1999 and 2003 to 23% between 2003 and 2012, as one reason why most new drug approvals were not subject to PREA requirements and potentially limited the impact of PREA.

“The law exempted drugs indicated for rare diseases, allowed deferred trials for drugs otherwise ready for use in adults, and permitted trial waivers for certain impractical circumstances, such as for diseases that do not affect children,” the researchers explained. They noted that adult rare disease exemptions after 2020 were eliminated by Congress, and Congress is also considering the Innovation in Pediatric Drugs Act to remove the rare disease exemption from PREA.

“This study suggests that elimination of the rare disease exemption may increase pediatric testing requirements for new drugs, although additional reforms may be necessary,” Liu and colleagues concluded.

JAMA Liu et al.

Study: Most new drugs subject to PREA requirements have ongoing postmarketing studies

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