Sponsor Initiated Requests to Delay Pediatric Postmarketing Studies.

BACKGROUND AND

OBJECTIVES

Lagging pediatric safety and effectiveness data increase the risks to children associated with off-label drug use. The objective of this study was to delineate the frequency of, and reasons behind, delays in the completion of mandated pediatric postmarketing requirement (PMR) studies.

METHODS

Publicly accessible and internal US Food and Drug Administration (FDA) data were aggregated to characterize pediatric PMRs issued from 2012 to 2024, including relevant dates, durations, and deferral extension (DE) requests. Sponsor size, and clinical trial enrollment status were also examined.

RESULTS

There were 1160 pediatric PMRs identified, 459 of which were associated with 1176 DE requests. Despite a significant decline in the annual number of PMRs issued (slope [95% confidence interval]: - 3.64 [- 6.50, - 0.79] year-1, p = 0.02), an increase in the annual number of DE requests (5.24 [2.16, 8.31] year-1, p < 0.01) was observed. Declines in negotiated timelines for PMR completion and durations of time granted per request were also seen. Issues related to clinical trial conduct predominated DE rationale in every year and accounted for 48% of all requests. One in 10 delayed trials failed to initiate enrollment before the PMR due date and 1 in 5 cited problems with clinical trial conduct before enrollment began. Smaller companies (< 500 employees) exhibited higher DE request rates, lower PMR success rates, and accounted for an increasing proportion of PMRs over the review period (from 17% in 2012 to 72% in 2024).

CONCLUSIONS

Year-on-year increases in DE requests reinforce ongoing challenges to timely and successful pediatric trial completion. Difficulties with clinical trial conduct appear to be the primary driver for these delays although the underlying root causes have yet to be elucidated. Regulators, sponsors, and stakeholder partners should work cooperatively to remediate delayed pediatric drug development timelines and reduce the duration of off-label drug use in children.