Pediatric studies and labeling additions required by the U.S. FDA for novel drugs approved from 2011 to 2023: a retrospective cohort study

Background The U.S. Food and Drug Administration (FDA) has the authority to require that sponsors conduct pediatric studies for certain new drugs under the Pediatric Research Equity Act (PREA). Here, we evaluate the characteristics and completion of these studies and assess the addition of pediatric-specific evidence generated from these studies into drug labeling. Methods and findings We performed a retrospective cohort study of all novel drugs approved by the FDA from 2011 to 2023 with at least one pediatric study requirement issued under PREA. Study status and outcomes were followed through 31 December 2024. We assessed completion of pediatric studies; addition of pediatric prescribing information to drug labels; and deviations from FDA-projected timelines. Of 552 novel drugs approved by the FDA between 2011 and 2023, 179 (32.4%) were subject to pediatric study requirements under PREA. Thirteen were later discontinued, resulting in a final cohort of 166 drugs and 338 pediatric study requirements. About half (51.8%) of the studies assessed efficacy. Among 222 studies with due dates by 31 December 2024, only 24.3% were completed by the original deadline. Over half (56.8%) received extensions of original timelines, by an average of 2.9 years (SD 2.0). At 10 years after drug approval, while 92.0% of studies were expected to have been completed, 59.5% had been completed. Of the 117 drugs with studies due by 31 December 2024, 54.7% (n = 64) had pediatric labeling updated with results from required studies. The mean time to addition of pediatric approval was 5.7 years (SD 2.6), whereas labeling additions reflecting lack of pediatric safety or benefit took an average of 8.3 years (SD 3.3) (p < 0.001). While 90.4% of drugs were expected to have all pediatric studies completed by 10 years, only 52.8% had any labeling changes reflecting data from the PREA-mandated studies. A limitation of this study is that publicly available FDA data provide limited detail on study design, execution, and reasons for delays, preventing assessment of study rigor and the factors contributing to delayed completion. Conclusions PREA was implemented to advance pediatric drug research and fill a critical gap in pediatric labeling of new drugs. However, our findings reveal frequent delays in study completion and labeling updates, with just over half of labeling additions completed 10 years after drug approval. Strengthening reporting requirements and expanding the FDA’s enforcement authority are essential to ensuring that children receive timely access to safe and effective therapies supported by high-quality evidence.