Stratification, Hypothesis Testing, and Clinical Trial Simulation in Pediatric Drug Development.
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.
McMahon, AW; Watt, K; Wang, J; Green, D; Tiwari, R; Burckart, GJ
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