RESUMEN
BACKGROUND: Placebo-controlled trials are the most rigorous method of evaluating the safety and efficacy of investigational treatments, yet the use of a placebo control in pediatric drug development is challenging and potentially controversial. Regulations provide additional protections for children participating in human subject research and limit the amount of risk to which children may be exposed without benefit (21 CFR 50, subpart D, Additional Safeguards for Children in Clinical Investigations). The objective of this paper is to describe the US Food and Drug Administration (FDA) experience with placebo-controlled trials conducted as part of pediatric drug development programs including compliance with 21 CFR 50, subpart D. METHODS: Pediatric drug development programs conducted under the Best Pharmaceuticals for Children Act (BPCA) or the Pediatric Research Equity Act (PREA) between 2012 and 2018 were reviewed. Trials that utilized a placebo control were identified and trial characteristics and risk mitigation strategies were extracted from publicly available sources. RESULTS: During this time frame, a total of 266 products were studied under pediatric product development initiatives. Of those, 67 products (25%) were studied in 96 individual placebo-controlled trials in pediatric patients. The majority of these studies included approaches to minimize risk to children in the placebo arm, including 49 trials that utilized placebo as an add-on to known effective therapy for the disease and 48 trials that included rescue therapy in the study protocol. CONCLUSIONS: When designed and conducted appropriately, placebo-controlled trials meet requirements under current US federal regulations for the protection of children in research.
