Exposure-Response Assessment in Pediatric Drug Development Studies Submitted to the US Food and Drug Administration

Clin Pharmacol Ther. 2020 Jul;108(1):90-98. doi: 10.1002/cpt.1809. Epub 2020 Mar 16.

Abstract

Exposure-response (E-R) modeling provides a quantitative tool to leverage adult data to support pediatric trial design and drug approval. The pediatric E-R studies submitted to US Food and Drug Administration (FDA) between 2007 and 2018 were surveyed in the context of various types of trial designs supporting drug approval in the pediatric population. The applications of E-R evaluation in pediatric drug development programs are mainly focused on three areas: (i) supporting pediatric extrapolation when the E-R relationships are similar between the pediatric and adult populations; (ii) dose selection to balance the risk-benefit profile based on the change in efficacy and safety response with different exposure levels; and (iii) approval of a new formulation, new dosing regimen, or new route of administration, where E-R evaluation helps quantify the change in clinical response between the old and new strategies. E-R modeling will continue to play an expanded role in pediatric drug development in the future.

MeSH terms

  • Adult
  • Age Factors
  • Child
  • Clinical Trials as Topic / methods
  • Drug Approval / legislation & jurisprudence*
  • Drug Development / methods*
  • Humans
  • Models, Biological*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics
  • Research Design*
  • United States
  • United States Food and Drug Administration

Substances

  • Pharmaceutical Preparations