By James E. Valentine* –
On September 10, 2014, the FDA hosted its 3rd Annual Patient Network Meeting, “Under the Microscope: Pediatric Drug Development,” to explore challenges related to pediatric drug development. The Patient Network is a program run out of FDA’s Office of Health and Constituent Affairs “to bring the unique perspectives of patients, family members, caregivers, and patient advocates to the decision-making processes of the FDA.”
The meeting consisted of a series of educational and interactive panel discussions, which discussed current regulations that encourage pediatric product development, as well as ways to advance pediatric drug development. While the meeting focused on patients and patient advocates, the discussions also included perspectives from regulators, industry, and academia.
Dr. Lynne Yao, Associate Director of the Pediatric and Maternal Health Staff in FDA’s Center for Drug Evaluation and Research’s Office of New Drugs, and Dr. Dianne Murphy, Director of FDA’s Office of Pediatric Therapeutics, set the stage for further discussion by presenting the historical framework and challenges for pediatric product development. There was a consensus that the Pediatric Research Equity Act ("PREA") and the Best Pharmaceuticals for Children Act ("BPCA") have helped facilitate the studies to support approved pediatric labeling (see here), and that the permanent reauthorization in FDASIA was a positive step forward.
Dr. Robert “Skip” Nelson, Deputy Director and Senior Pediatric Ethicist of FDA’s Office of Pediatric Therapeutics, provided an overview of the ethical framework and regulatory protections for children in research, consisting of (1) scientific necessity, (2) appropriate balance of risk and benefit, (3) parental permission, and (4) child assent.
Throughout the course of the panel discussions, a series of challenges to pediatric product development arose from both the regulatory and industry perspectives. An underlying problem is that pediatric studies, like studies of orphan drugs, enroll subjects from a small population. As a result, there are fewer subjects to enroll in studies, and there may be a limited ability to recoup costs of development and formulations.
Additionally, it is more difficult to conduct pediatric trials due to the need for multicenter and often international studies in order to enroll adequate numbers of patients, as well as the need for special facilities, equipment, nurses, laboratories, and expertise. Also, studies require many age subsets or subset analyses because pediatrics covers a wide range of organ developmental maturation, which may affect drug pharmacokinetics, efficacy, and safety. Other challenges include the need for juvenile animal studies, age-appropriate pediatric formulations, and age-appropriate and validated pediatric endpoints and assessment tools.
Some recommendations from patients, regulators, industry, and academia included:
- A need for the entire pediatric community to insist on incorporation of evidence based treatment sufficient to support pediatric labeling;
- Development of simplified pediatric networks to conduct appropriate clinical trials;
- Education of caregivers about the importance of clinical trial enrollment, understanding the role of a control arm, and the option and ramifications of “opting out;”
- The need for flexibility by FDA in the design of pediatric studies, especially to relieve the tension with formulation development; and
- Increased patient and caregiver input in FDA and industry’s planning and decision-making (i.e., caregiver input on protocols, caregiver participation in protocol simulations).
Ultimately, there was accord among the meeting participants that you protect children not from studies but with studies.
*Not admitted to practice in Washington, D.C.