Pediatric drug development: unmet medical needs and opportunities for collaboration between industry, academia and the US FDA

Abstract

The needs and advances in pediatric drug development have burgeoned since Shirkey initially referred to children as ‘therapeutic orphans’ [1]. Owing to requirements and incentives to investigate and develop therapeutic classes of molecules in children, drug development involving pediatric patients has risen steadily. The requirements are the result of the Pediatric Research Equity Act and the incentives are from the Best Pharmaceuticals for Children Act, two pieces of legislation that are set to expire in 2012 [101]. Pediatric Research Equity Act and Best Pharmaceuticals for Children Act have resulted in a total of 335 written requests issued (1998–July 2011), 323 marketing applications approved with postmarketing requirements (through May 2011) and 415 labels changed (1998–July 2011). From a global development perspective, ongoing collaborations between the US FDA and the other regulatory agencies, including the European Medicines Agency, facilitate these advances in pediatric product development. The significant role of personnel exchanges (short-term), working groups between both agencies, European Medicines Agency Non-clinical and Formulations Working Groups and expert meetings and workshops (including FDA representatives) and WHO initiatives, are helping to facilitate critical involvement and participation. Other collaborative networks between global regulatory partners include the Pediatric Regulators Network and Essential Medicines for Children Activities, Japan’s Pharmaceuticals & Medical Devices Agency as observers in the FDA’s and European Medicines Agency’s pediatric collaboration and the FDA and NIH collaboration to develop a publicly available framework on pediatric formulations. One important area for further development is the understanding of biomarkers and surrogate markers and their applications to pediatric clinical trials and drug development. The lack of appropriate parameters for pediatric clinical trials in children with gastrointestinal disease has resulted in the lack of appropriate end point identification and delays in pediatric product development. This is an area that would benefit from earlier attention in the overall development process. A renewed commitment to identify appropriate drug candidates and plan a process for approval for children is needed. Of the total products studied and labeled under US pediatric legislation, drugs with pediatric gastroenterology labeling account for only 8.6% (n = 11). Drug classes studied included treatment of hyper cholesterolemia, inflammatory bowel disease, vomiting, obesity and hepatitis B and C and acid blockade