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Original Investigation
November 19, 2018

Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act

Author Affiliations
  • 1Pediatric Therapeutics and Regulatory Science Initiative, Boston Children’s Hospital, Boston, Massachusetts
  • 2Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 3Computational Health Informatics Program, Boston Children’s Hospital, Boston, Massachusetts
  • 4Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
JAMA Pediatr. Published online November 19, 2018. doi:10.1001/jamapediatrics.2018.3416
Key Points

Question  What are the characteristics, completion rate, and transparency of pediatric postmarketing studies required under the US Pediatric Research Equity Act for drug approvals from 2007 to 2014?

Findings  This cohort study found that only 33.8% of pediatric postmarketing studies mandated by the Pediatric Research Equity Act have been completed after a median follow-up of 6.8 years, and 41.2% of drug labels include any pediatric data. Information about the characteristics and study design could not be identified for 33% of pediatric studies.

Meaning  Many pediatric studies mandated by the Pediatric Research Equity Act are not completed in a timely fashion, and many drug labels continue to lack any pediatric information.

Abstract

Importance  Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies.

Objective  To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act.

Design and Setting  A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications.

Main Outcomes and Measures  Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models.

Results  Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information.

Conclusions and Relevance  Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.

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