Stratification, Hypothesis Testing, and Clinical Trial Simulation in Pediatric Drug Development.


Journal Article

BACKGROUND: Pediatric drug development is plagued by small sample sizes, unvalidated clinical endpoints, and limited studies. OBJECTIVES: The objective of this study was to determine whether age stratification within the pediatric population could be used to (1) assess response to a pharmacologic intervention and to (2) design future trials based upon published stratified disease data using clinical trial simulation (CTS). METHODS: Data available from the literature for Kawasaki disease (KD) was used in the model. Age-stratified CTS for a theoretical new drug was conducted. RESULTS: Population-specific differences due to age might affect trial success if not taken into account. CTS predicted inflammatory indices, and inclusion cutoff significantly altered the trial outcome. Finally, altered pharmacokinetics/pharmacodynamics in varying age groups of KD patients may alter drug exposure and response. CONCLUSIONS: If assumptions regarding a pediatric disease process, such as KD, do not include age stratification with inclusion or response, then the wrong decision could result with regard to age-appropriateness or approval of a drug.

Full Text

Cited Authors

  • McMahon, AW; Watt, K; Wang, J; Green, D; Tiwari, R; Burckart, GJ

Published Date

  • 2016

Published In

Volume / Issue

  • 2016 /

PubMed ID

  • 27774353

Pubmed Central ID

  • 27774353

International Standard Serial Number (ISSN)

  • 2168-4790

Digital Object Identifier (DOI)

  • 10.1177/2168479016651661


  • eng

Conference Location

  • United States