Drug labeling changes and pediatric hematology/oncology prescribing: Measuring the impact of U.S. legislation

Clin Trials. 2021 Dec;18(6):732-740. doi: 10.1177/17407745211030683. Epub 2021 Jul 16.


Background/aims: The Pediatric Research Equity Act and Best Pharmaceuticals for Children Act are intended to promote the conduct of clinical trials that generate pediatric-specific evidence about drug safety and efficacy. This study assesses the quality of evidence generated through Pediatric Research Equity Act-mandated and Best Pharmaceuticals for Children Act-incentivized clinical trials of hematology/oncology drugs and characterizes subsequent changes in pediatric drug utilization rates.

Methods: Trial characteristics (blinding, randomization, and comparator group) were determined for clinical trials that supported pediatric label changes. Using data from OptumLabs® Data Warehouse, a de-identified administrative claims database, we calculated pediatric utilization rates for each drug. We calculated monthly utilization rates from January 2003 (or from the first month in which data were available) to December 2018.

Results: We identified 11 hematology/oncology drugs that underwent pediatric label changes under the Pediatric Research Equity Act Pediatric Research Equity Act and/or Best Pharmaceuticals for Children Act, and we identified 15 trials supporting these changes. Of these trials, 36% (5/14) were randomized, 31% (4/13) were blinded, and 36% (5/14) used a comparator group. A median of 49 children (interquartile range 29.5) received the drug under investigation across these trials. Pediatric label changes were not associated with subsequent changes in pediatric drug utilization. Although some drugs saw increased pediatric use after gaining new pediatric indications, this pattern was not consistently observed. In addition, there was no evidence to suggest that drugs were utilized less frequently after they failed to receive pediatric indications.

Conclusions: Clinical trials of hematology/oncology drugs conducted under the Pediatric Research Equity Act Pediatric Research Equity Act and Best Pharmaceuticals for Children Act generally have low methodological rigor, and the resulting label changes are not consistently associated with changes in pediatric utilization. Alternative regulatory strategies and study designs may be necessary to maximize the impact of newly generated knowledge on drug utilization.

Keywords: Clinical trials as topic; drug approval; health policy; pediatrics.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Child
  • Drug Approval
  • Drug Labeling*
  • Hematology*
  • Humans
  • Medical Oncology
  • United States
  • United States Food and Drug Administration