FDA has endorsed extrapolation of therapeutic efficacy from adults to children for new drugs to treat partial onset seizures in a draft guidance and is now discussing in public meetings whether the approach can be extended to other indications, such as heart failure and pulmonary arterial hypertension.
Doing so on a large scale may require companies to change the way they study drugs in adult populations. Extrapolation depends upon evidence of similarity between adults and children, but sponsors do not routinely collect the necessary evidence in adult studies.
Pediatric drug approvals have lagged adult approvals despite laws and regulations intended to spur or mandate pediatric clinical research.
By law, companies must submit pediatric development plans to EMA once a drug has completed Phase I testing, and to FDA after Phase II. Japan’s PMDA does not require companies to perform pediatric studies, but offers extended market exclusivity and data protection as an incentive.
Even so, according to FDA, U.S. drug approvals for children continue to trail approvals for adults by about eight years, and off-label drug use dominates clinical practice. By some estimates, about half the drugs used in children and 90% of the drugs used in neonates have never been studied in those populations.
Reasons include difficulty recruiting enough pediatric patients for trials, the limited commercial potential of small pediatric markets, and risk-averse thinking that emphasized children’s protection to the point of excluding them from research.
“If we have to do a randomized multisite controlled trial for every single indication and every drug, we could never catch up.”
Efficacy trials in children