Useful pharmacodynamic endpoints in children: selection, measurement, and next steps

Pediatr Res. 2018 Jun;83(6):1095-1103. doi: 10.1038/pr.2018.38. Epub 2018 Apr 18.


Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Evaluation / methods
  • Drug Evaluation / standards*
  • Drug Therapy / methods*
  • Drug Therapy / standards
  • Endpoint Determination
  • Health Policy
  • Humans
  • Infant
  • Infant, Newborn
  • Patient Compliance
  • Pharmaceutical Preparations
  • Pharmacokinetics
  • Pharmacology / methods*
  • Practice Guidelines as Topic
  • Reproducibility of Results
  • Research Design
  • Risk
  • United States
  • United States Food and Drug Administration


  • Biomarkers
  • Pharmaceutical Preparations