FDA Analysis Shows Similar Success Rates for Pediatric Trials Using Clinical and Surrogate Endpoints
An analysis by US Food and Drug Administration (FDA) officials published earlier this month finds that there is a similar success rate for pediatric pivotal trials relying on surrogate endpoints compared to trials that use clinical endpoints.While the authors find the use of surrogate endpoints in pediatric trials is effective, they argue that it is critical for endpoints that are unique to pediatric studies to be validated, as a higher proportion of pediatric studies that used a different endpoint than the corresponding adult trial failed.
Background
Prior to efforts to incentivize pediatric drug development beginning with the Written Request program under the Food and Drug Administration Modernization Act (FDAMA) in 1997, very few pediatric studies were conducted.
In 2003, the Pediatric Research Equity Act (PREA) was passed, requiring drugmakers to conduct pediatric trials when a drug's indication in adults also exists in pediatric patients.
Since then, more than 1,200 pediatric trials have been submitted to FDA, though drugmakers are able to obtain waivers for conducting pediatric studies under certain circumstances, and the agency only recently closed a loophole that allowed drugmakers to bypass pediatric study requirements by obtaining orphan designation for a pediatric subpopulation of a more common disease in adults.
Surrogate Vs. Clinical Endpoints
The goal of the analysis was to determine whether the outcomes of pediatric trials involving surrogate endpoints varied from those using clinical endpoints in light of provisions in the 21st Century Cures Act that encourage the use of surrogate endpoints to accelerate drug development.
To do so, the authors looked at trials submitted to FDA under the Food and Drug Administration Amendments Act (FDAAA) and the FDA Safety and Innovation Act (FDASIA) spanning from September 2007 to July 2016.
The authors identified 121 pivotal pediatric efficacy studies during this period after excluding studies that did not have a corresponding adult trial for the same indication and studies that relied on extrapolation of efficacy from another population.
Of those studies, 45 (37%) used surrogate endpoints, 66 used clinical endpoints (55%) and 10 (8%) included both surrogate and clinical endpoints.
The use of surrogate endpoints varied by therapeutic areas, with some, such as hematology, oncology and inborn errors exclusively using surrogate endpoints while others such as psychiatry, dermatology and neurology used only clinical endpoints.
The success rates for those trials were similar across the board. Eighty-two percent of trials using surrogate endpoints were successful, while 77% of trials using clinical endpoints were successful and 80% of trials with both types of endpoints were successful.
Studies were more likely to be successful if the endpoint was the same in the corresponding adult trial (86% success), whereas only 64% of studies that used a different endpoint from the corresponding adult trial were successful.
"One possible explanation for this observation is that the unique pediatric endpoints have not been validated for use in a drug development program, in contrast to endpoints that have been previously used in adult studies," the authors write.
Clinical Pharmacology & Therapeutics
Pediatric Exclusivity Statistics