The FDA: Faster, but not necessarily better. And that could threaten the agency's brand
Faster FDA drug approvals may reflect less rigorous evidentiary standards, a new analysis suggests.
In 1962, the regulatory scrutiny of medicines by the FDA intensified in reaction to thalidomide, an anti-nausea drug that gained notoriety after its link to severe skeletal birth defects. Since then, a flood of incentives has made the US system of getting drugs approved easier and the agency seemingly more flexible. Regulatory incentives — such as fast-track and breakthrough therapy status, orphan drug designations as well as accelerated and conditional approvals — have diminished review times and encouraged the use of surrogate endpoints. And while the industry has encouraged it, some researchers see a downside.
The analysis, conducted by Jonathan Darrow and others and published in JAMA on Tuesday, found that that this evolution has led to the FDA generally accepting less robust evidence, all the while shortening its review times.
The data show that the classic FDA “gold standard” of accepting new drug applications based on at least two pivotal trials has fallen from 80.6% in 1995-1997 to 52.8% in 2015-2017. Meanwhile, medicines brandishing the “orphan drug” tag — often signaling less rigorous standards — have risen from 18% over the period of 1984 to 1995 to 41% between 2008 and 2018.
FDA drug review times have declined from more than 3 years in 1983 to less than 1 year in 2017 (although the total time to get a drug ready for review has remained steady), the authors highlighted.
If drugs approved with less evidence turn out to be problematic it may lead to “an erosion of the ‘FDA approved’ brand,” Darrow told Reuters.
“If the standards are different than they were in the past, it’s important for patients and physicians to be aware of that,” Darrow said in an interview with the wire service. “Patients and physicians need to focus on the evidence and not the fact of FDA approval. How big are the benefits, and how certain are we of the benefits?”
While some of these new drugs have been remarkable advances for debilitating and often deadly diseases, “high prices at the high end or in excess of independently assessed measures of value have created barriers to access,” Joshua Sharfstein from Johns Hopkins Bloomberg School of Public Health pointed out in a JAMA editorial in response to the analysis by Darrow et al.
Overall, the average annual number of new drug approvals, including biologics, has seesawed — from 34 between 1990 and 1999 to 25 from 2000 to 2009 and 41 from 2010 to 2018, authors of the analysis found. One heartening data point is the median annual number of generics — copycat approvals accelerated from 284 — prior to the Generic Drug User Fee Act of 2012 — to 488 between 2013 and 2018.
To accommodate the higher volume of drug manufacturers, the FDA in 1992 was granted the power to collect fees for their reviews. Now, the annual fees collected under Prescription Drug User Fee Act (PDUFA) have jumped from $29 million in 1993 to $908 million in 2018, the data showed.
Critics have admonished the sliding door between executives in the biopharmaceutical industry and the FDA, and underscore that the transactional interaction between the agency and the industry does not bode well for an independent, unbiased review of products.