Related Experiment Video
Updated: Dec 9, 2025
A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Ethical Considerations for Pediatric Placebo-Controlled Trials: FDA Outcomes and Perspectives
Jeremiah D Momper1, Dionna J Green2, Kyunghun Park3
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Insights
Placebo-controlled trials in pediatric drug development are feasible and ethical when designed with risk mitigation strategies. The U.S. Food and Drug Administration (FDA) has experience ensuring compliance with child protection regulations in these studies.
Area of Science:
- Clinical Pharmacology
- Pediatric Research
- Regulatory Science
Background:
- Placebo-controlled trials are the gold standard for evaluating treatment safety and efficacy.
- Pediatric drug development faces unique ethical challenges and regulatory protections for child participants.
- U.S. regulations (21 CFR 50, subpart D) limit risks to children in research without direct benefit.
Purpose of the Study:
- To describe the U.S. Food and Drug Administration (FDA) experience with placebo-controlled trials in pediatric drug development.
- To assess compliance with regulatory safeguards for children in these trials (21 CFR 50, subpart D).
Main Methods:
- Review of pediatric drug development programs under the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA) from 2012-2018.
- Identification of trials using placebo controls in pediatric patients.
- Extraction of trial characteristics and risk mitigation strategies from public sources.
Main Results:
- Out of 266 products studied, 67 (25%) involved 96 placebo-controlled trials in children.
- Most trials incorporated risk minimization, such as add-on therapy (49 trials) or rescue medication (48 trials).
Conclusions:
- Appropriately designed and executed placebo-controlled trials can meet regulatory requirements for protecting children in research.
- These trial designs demonstrate a commitment to ethical pediatric drug development while ensuring scientific rigor.
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.
Related Concept Videos
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:25Drug Regulation
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:11Clinical Trials: Overview