Systematic Review of Early Phase Pediatric Clinical Pharmacology Trials

Abstract

OBJECTIVE Children have generally been excluded from early-stage clinical trials owing to safety concerns based in social expectations and not data. However, the repositioning of adult therapeutics for pediatric use and the increase in the development of therapies for pediatric only conditions require the participation of children in phase 1-2 trials. Therefore, the aim of this article is to systematically review the history and current state of early phase pediatric clinical pharmacology trials in order to understand safety concerns, trends, and challenges in pediatric trials. METHODS This review analyzed the nature of early phase pediatric clinical trials conducted for nononcology conditions through a systematic search that was performed for pediatric non-oncologic phase 1 or phase 1-2 drug and vaccine studies in MEDLINE. RESULTS The data show that the number of early phase pediatric clinical trials is still small relative to adults but has been on the rise in the past decade with relatively few serious adverse effects observed. CONCLUSIONS The widespread concerns about children’s safety when they participate in early phase clinical trials seem disproportionate, based on our findings. The data confirm that these studies can be conducted safely, and that their results can contribute significantly to pediatric pharmacotherapy. ABBREVIATIONS AIDS, acquired immune deficiency syndrome; BPCA, Best Pharmaceuticals for Children Act; CI, confidence interval; HIV, human immunodeficiency virus; LMIC, low-to-middle-income country; RCT, randomized clinical trial; SPC, summary of product characteristics; US, United States; FDA, Food and Drug Administration.