The NIH has released a new "Priority List" of pediatric therapeutic areas and medical products it wants the medical community—including the pharmaceutical and biopharmaceutical industries—to focus on.
Historically, many companies seeking product approval in the U.S. avoided clinical studies involving children, wary of ethical problems, a lack of incentives and the potential consequences if testing uncovered new problems. As a result, many products lacked adequate dosing or safety information for children.
"We all know that children are not just small adults," said Lynne Yao, associate director of pediatric and maternal health staff in the FDA’s Center for Drug Evaluation and Research’s (CDER) Office of New Drugs (OND). Some drugs may be super-potent in children relative to adults, while others may not work at all. In either case, there are inherent safety risks.
To remedy this situation, Congress enacted two critical pieces of legislation: The Best Pharmaceutical for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), which combined provide new exclusivity-based incentives to conduct studies (BPCA), and allow the FDA to require companies to conduct pediatric studies as a condition of approval (PREA).
"Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children," said Yao. "Today that number has been reduced to about 50%."
But the two laws differ in an important way: PREA requires companies to conduct post-market evaluations of their drugs in children, whereas the BPCA creates voluntary incentives for similar evaluations.
The BPCA, a 2002 law reauthorized in 2007 and 2012, allows the FDA to request a sponsor of a new drug study that product's effects in children. As NIH explained in a 2012 Federal Register notice, a lack of pediatric data "can increase a child's risk for unknown and/or adverse effects."
That's where the BPCA comes into play. In return for a sponsor conducting requested pediatric studies, a company becomes eligible for an additional six months of market exclusivity for a product's indication—the whole indication, and not just for its pediatric population. For blockbuster drugs that might generate billions in sales each year, the extra six months of exclusivity can be a powerful incentive.
But not all companies decide to take advantage of these incentives, often citing a lack of interest, ethical or legal concerns, difficulty enrolling patients or a lack of profit.
To address those cases, the BPCA also directs the NIH's National Institute of Child Health and Human Development (NICHD) to compile the Priority List of Needs of Pediatric Therapeutics (PLNPT) at least once every three years. Each year, the NICHD focuses on three therapeutic areas, it said.
The list, according to the NIH, represents the "drugs and therapeutic areas of highest priority for study in pediatric populations."
Once identified, the NIH and the FDA (or a sponsor) will develop Proposed Pediatric Study Requests (PPSRs) soliciting a manufacturer to conduct research on a drug in return for additional market exclusivity. If the manufacturer declines, the NIH will attempt to conduct its own research on the drug to better inform pediatric labeling.
The NIH has released its latest PLNPT for 2014, reflecting 17 categories of elevated need. The list includes 88 priority therapeutic areas, including several new ones such as sildenafil (Viagra), epogen, fluconazole (Diflucan) and epinephrine.