title: Stratification, Hypothesis Testing, and Clinical Trial Simulation in Pediatric Drug Development.
abstract: BACKGROUND
  Pediatric drug development is plagued by small sample sizes, unvalidated clinical endpoints, and limited studies.
  
  
  OBJECTIVE
  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.
authors: Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration, Silver Spring, MD, USA.
authors: Ann W
authors: AW
authors: McMahon
authors: Duke University Medical Center, Durham, NC, USA.
authors: Kevin
authors: K
authors: Watt
authors: Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, MD, USA.
authors: Jian
authors: J
authors: Wang
authors: Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, MD, USA.
authors: Dionna
authors: D
authors: Green
authors: Office of Biostatistics, Office of Translational Sciences, Food and Drug Administration, Silver Spring, MD, USA.
authors: Ram
authors: R
authors: Tiwari
authors: Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, MD, USA.
authors: Gilbert J
authors: GJ
authors: Burckart
keywords: Kawasaki disease; age groups; modeling; pharmacokinetics pharmacodynamics