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SP09-71: Improving Pediatric Prescribing: Measuring the Impact of Legislative Initiatives

Poster Presenter

      Tyler Benning

      • Medical Student
      • Mayo Clinic
        United States


To examine clinical trials conducted under the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) and assess changes in pediatric drug utilization rates following PREA and BPCA-associated clinical trials.


Hematology-oncology drugs approved from 2001-10 which underwent pediatric labeling changes were identified. PREA compliance and methodology of underlying trials were assessed. Using OptumLabs claims data, pre- and post-label change utilizations were compared using chi2 tests and two-sided p-values.


Among 15 trials under PREA/BPCA that supported 11 label changes, 36% (5/14) were randomized, 31% (4/13) were blinded, 36% (5/14) were controlled, and 21% (3/14) were phase III trials. Due to data confidentiality rules, exact utilization rates were not reportable for drugs with very low utilization rates, but p-values were reportable for all comparisons. One drug was excluded from analysis because it lacked at least one year of pre- and post-change utilization data. Seven of ten (70%) drugs received positive label changes granting new pediatric indications. Subsequently, 4 of these 7 drugs (57%) were associated with statistically significant increases in pediatric utilization (p < 0.05). Absolute utilization changes for these 4 drugs ranged from +0.7 to +1.18 unique children utilizing per 100,000 children, representing relative changes ranging from +25.0% to +319%. Three of these 7 drugs were not associated with statistically significant increases in utilization, with absolute changes ranging from -0.29 to +0.16 children per 100,000 children and relative changes ranging from -32.2% to +94.1%. Two of 10 (20%) drugs received negative label changes stating that they were not indicated in children for safety and/or efficacy reasons. One of these drugs was associated with a significant increase in utilization (p < 0.001, absolute change +0.77 children/100,000 children, relative change +167%). The other was associated with a non-significant increase in utilization (p > 0.05, exact utilization not reported). One of 10 (10%) drugs received a neutral label change stating that the drug’s safety and efficacy in pediatric patients could not be determined. This drug was associated with a statistically significant increase in pediatric utilization (p < 0.01, exact utilization not reported). Of the 6 drugs approved after the passage of PREA, 5 received permanent exemptions or waivers from PREA pediatric reporting requirements, and one received a temporary deferral.


Legislative efforts such as PREA and BPCA assume that label changes are an effective mechanism for influencing prescribing patterns. However, among drugs receiving clear positive or negative label changes under PREA/BPCA, only 4 of 9 (44%) were associated with statistically significant utilization changes in the expected direction. This disconnect between labeling changes and subsequent changes in utilization may be partially driven by the weak methodology of the clinical trials that support these label changes. Long delays between adult approvals and pediatric trials may also weaken the impact of pediatric trials and label changes. All six drugs approved after the passage of PREA received some type of waiver or deferral of PREA’s pediatric reporting requirement. However, these drugs were ultimately successfully studied in children, suggesting that pediatric trials were both feasible and warranted. In order to strengthen PREA and BPCA, policy makers should consider tightening temporal requirements for the completion of clinical trials, and they should consider narrowing the grounds under which PREA exemptions and waivers are granted.