Many drugs granted accelerated approval by the U.S. Food and Drug Administration (FDA) lack clear evidence of safety and effectiveness, and the same is true for most high-risk medical devices, according to two new reports in JAMA, online August 15.
The Accelerated Approval pathway makes potentially promising investigational medicines available for use before the usual amount of data has been collected to confirm their effectiveness and safety, Dr. Huseyin Naci from the London School of Economics and Political Science told Reuters Health by email.
“Drugs granted Accelerated Approval should be rigorously evaluated using convincing patient-centered clinical outcomes in rigorous studies,” Dr. Naci said. But, he added, “we have found numerous situations in which required confirmatory studies with rigorous designs and outcomes are not pursued or are not completed in a timely fashion, and in these cases, we are concerned that regulators appear to accept data that would not otherwise meet FDA standards.”
Dr. Naci’s team analyzed the FDA’s accelerated approval of 22 drugs for 24 medical conditions.
For standard approval, the FDA generally requires gold-standard randomized controlled trials (RCTs) that demonstrate a drug’s safety and effectiveness. Fourteen of these accelerated approvals, however, were exclusively based on less-rigorous trials.
Given the lower standard of evidence, the FDA required 38 more trials after approval to confirm the benefits of these drugs. Three years after approval, though, only 19 had been completed. Eleven more were underway and said to be on schedule, six others were delayed by more than 12 months, and two had been discontinued.
Most of these later trials still used outcomes that would not be acceptable for standard approval, and several studies failed to show a benefit or were terminated early. For the 10 approvals that finally met the requirements established by FDA, the time to do so ranged from one to five years after the accelerated approval.
“Our findings suggest that expediency in drug development and approval can be successful but that drugs approved via the shorter route to market are rarely subject to tests, even in the post-approval period that use established and clinically meaningful outcomes,” Dr. Naci said.
When the FDA approves medicines via its Accelerated Approval pathway, he said, the agency should clearly specify the data limitations and how required confirmatory studies are expected to compensate for these limitations.
A second report from Dr. Rita F. Redberg of the University of California, San Francisco, and colleagues paints a similar picture for high-risk medical device supplements, which are required for any change that might affect safety and effectiveness. These always require clinical data.