Specialized programs developed by the FDA in the 1980s and 1990s appear to have lowered the bar for approving certain types of drugs, researchers found.
For example, after the passage of the 1983 Orphan Drug Act, which made regulatory standards more flexible when considering drugs for rare diseases, the trials that formed the basis of approvals for rare disease drugs were smaller (96 vs 290 participants), and more frequently nonrandomized (30% vs 80%) and unblinded (4% vs 33%) compared with trials of drugs for common diseases, reported Jonathan Darrow, JD, MBA, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
Similarly, as shown in a “special communication” review in JAMA, drugs designated to have “breakthrough status” were approved in almost half the time as drugs that did not have that status (4.8 vs 8 years), and 52% of drugs in this program approved in the years 2013-2016 relied on an evidence base from phase I or II trials. Another 45% had an evidence base consisting of a single trial and 42% relied on trials that did not have an active or placebo control, Darrow and co-authors reported.
Overall, 52.8% of drugs approved in 2015-2017 were supported by evidence from at least two pivotal trials, down from 80.6% in 1995-1997, the researchers found.
Surrogate measures — like glycated hemoglobin levels for diabetes medications or forced expiratory volume in one second for cystic fibrosis drugs — have also been increasingly used in drug trials, up from 44.3% in 2005-2012 to 59.3% in 2015-2017, the investigators added.
The results showed that the use of special development and approval programs — including the Orphan Drug Act, Accelerated Approval, Fast Tracking, Priority Review, and Breakthrough Therapies — is increasing, such that 48% of drugs qualified for one of these programs in 1986-1996 and more than 80% of drugs in 2018 did.
The current regulatory standards for FDA approval require that new drugs “have the effect it purports or is represented to have,” supported by evidence from “adequate and well-controlled investigations,” but these definitions rely almost entirely on the agency’s interpretation, Darrow told MedPage Today.
“While these words have not changed since 1962, what has changed is the formal approach the FDA takes when interpreting them,” he said. “That means the standard for drug approval has, in fact, changed.”
The proportion of the FDA’s budget for drug and biologics oversight that came from user fees reported in this study was surprisingly high, noted Steven Joffe, MD, MPH, of the University of Pennsylvania in Philadelphia, who was not involved with the research.
Drug companies paid $4.1 billion in user fees in years 2013-2017, up from $330 million in 1993-1997, the researchers reported. In 2018, user fees from the drug industry accounted for 80% of the FDA reviewers’ salaries….