Hypothalamic-Pituitary-Adrenal Axis Pediatric Safety Studies Submitted to the FDA.

ABSTRACT

BACKGROUND: Corticosteroid use has been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression which can predispose the pediatric patient to multiple immune- and growth-related adverse effects. The objectives of this review were to identify the pediatric drug development programs involving corticosteroids and the associated pediatric HPA axis suppression studies submitted to the US Food and Drug Administration (FDA), capture FDA guidance topic related recommendations, and determine the consistency of HPA axis data in prescription corticosteroid labeling. METHODS: A review of FDA submissions from January 2002 to July 2018 involving corticosteroid products and HPA axis testing in pediatric patients was conducted. The adrenal function testing methods, number of pediatric HPA axis dedicated studies, duration of these studies, and the labeling outcomes were assessed. RESULTS: Of the 437 total drug products that were submitted to FDA, only 36 products were corticosteroids or a corticosteroid combination product yielding a total of 83 pediatric clinical studies. Twenty-four of the 36 products included 37 HPA axis suppression dedicated studies which employed different measurement methods. The pediatric HPA axis suppression trial data collected did not necessitate any new actionable recommendations in the FDA labeling. CONCLUSION: Future pediatric drug development program goals would be to determine whether HPA axis suppression studies should be conducted, establish optimal testing methods if HPA axis testing is performed, continue to update guidances for industry, and actionable labeling recommendations. However, regulatory policy related to conducting pediatric HPA axis studies requires additional scientific research and discussion by the pediatric drug development community.