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Many drugs prescribed to children have not been formally studied or approved for pediatric use, leaving clinicians without age-specific, high-quality clinical trial data to inform dosing, safety, and efficacy.1–3 The 2003 Pediatric Research Equity Act (PREA) authorizes the US Food and Drug Administration (FDA) to require pediatric studies for certain drug and biological products.4,5 Since its enactment, PREA has been impactful: between September 2007 and December 2019, 937 studies were completed under PREA, catalyzing pediatric research and contributing to important prescribing information across a range of products.6 However, delays in fulfilling PREA requirements are well documented.1–3,7 Up to 64% of new drugs lack pediatric labeling 5 years after approval, and only one-third of required studies are completed after a median of nearly 7 years.1,2To enforce PREA, the FDA has the authority to issue noncompliance (NC) letters when sponsors fail to meet deadlines specified in postmarketing requirements (PMRs). An NC letter may be issued when a sponsor fails to (1) submit a required pediatric assessment within the specified timeframe (ie, provide pediatric study data); (2) request, with adequate justification, a waiver or deferral of the required studies; or (3) submit a request for approval of a required pediatric formulation.4 The effectiveness of NC letters has not been well studied. We examined all PREA-related NC letters issued between 2015 and 2023 and identified patterns in sponsor responses and postmarketing study status.We conducted a retrospective review of NC letters issued under PREA between January 1, 2015, and December 31, 2023, using 4 publicly available FDA resources (Supplemental Table 1). Sponsors were classified as brand, generic, or other; each PMR was classified by status, study type, and age group (Table 1; Supplemental Table 2). Sponsor-reported explanations for NC were categorized into themes using inductive content analysis with iterative refinement and independent verification. Data were extracted by one author and verified by another, and discrepancies were resolved by consensus. Expanded methods are provided in the Supplemental Materials.Between 2015 and 2023, the FDA issued 100 NC letters to 74 sponsors referencing 74 products and 122 PMRs (Supplemental Table 3). PMRs spanned all pediatric age groups, with required study types including safety (32%), pharmacokinetic/pharmacodynamic (26%), and efficacy (20%). At the time of data collection, 58 noncompliant PMRs (48%) remained delayed, 16 (13%) were fulfilled, 9 (7%) were submitted, and 13 (11%) were released (Table 1). Seven letters referencing nine PMRs received no response. Median time from product approval to NC letter issuance was 6.8 years (interquartile range [IQR], 4.6–9.4) and median time to sponsor response was 41 days (IQR, 28–47).Common reasons for NC included protocol or study design challenges (n = 25), no explanation provided (n = 23), and enrollment difficulties (n = 19). Seventeen sponsors attributed delays to the COVID-19 pandemic (Table 2; Supplemental Table 4).Although PREA has advanced pediatric research, our analysis highlights persistent gaps in enforcement. Nearly half of PMRs remained delayed even after NC letter issuance, indicating that the FDA’s current enforcement power is insufficient to ensure the timely completion of mandated pediatric studies. These delays leave patients and clinicians without age-specific, high-quality clinical trial data to guide prescribing.Noncompliant PMRs spanned a wide range of products, study types, and age groups, underscoring established systemic obstacles in pediatric drug development.1–3,8,9 Sponsor explanations for NC most often reflected feasibility challenges rather than regulatory resistance. This pattern highlights opportunities for targeted solutions such as innovative trial designs, investment in pediatric formulations, and strategies to improve enrollment.This work also highlights a lack of available data. The total number of delayed or otherwise incomplete pediatric PMRs is not publicly reported, limiting the ability to place NC letters in the broader context of PREA enforcement. Greater data transparency and enhanced enforcement authority would strengthen FDA oversight and help ensure timely access to safe and effective therapies for children.The authors appreciate assistance in data collection provided by Jay Crawford, Samantha Girschick, and Addie Morgan.