The FDA Is Approving Drugs Faster, But That May Not Be A Good Thing

FDA Approval

In a second research report published this year so far, investigators found that the U.S. Food and Drug Administration (FDA) is approving drugs faster than ever. Unfortunately, it appears that the agency is also approving those drugs on less data and weaker evidence.

The first study published in the journal SSRN was by researchers at Harvard University, the University of Texas at Dallas, and the Massachusetts Institute of Technology (MIT). It questioned if the FDA and other regulatory agencies worldwide don’t rush certain approvals, particularly at the end of the year in a kind of “desk-clearing” activity.

The report notes, “In the United States, the number of December drug approvals is roughly 80% larger than in any other month. Similar approval spikes occur at the end of each calendar month. Additionally, approvals spike before holidays, such as before Thanksgiving in the United States and the Chinese New Year in China (but not vice versa).”

And more troubling is that there appears to be a correlation with more problems with these drugs. Lauren Cohen, a professor of finance and entrepreneurial management at Harvard Business School and one of the authors, told the Wall Street Journal, “We see about twice as many adverse effects.”

The second study appeared in the journal JAMA Network and was conducted by researchers with Harvard Medical School. The lead author, Jonathan Darrow, a lawyer with the medical school’s Program on Regulation, Therapeutics and Law, told NPR, “There has been a gradual erosion of the evidence that’s required for FDA approval.” He points out that patients and physicians “should not expect that new drugs will be dramatically better than older ones.”

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The study notes that about half of recent drug approvals were built on a single pivotal clinical trial. Typically, two pivotal, Phase III trials were the norm. In addition, the study says that surrogate measures, which are utilized as stand-ins for presumed patient benefits, has grown. For example, in oncology drugs, what most patients would want are improvements in survival after receiving treatment. But some cancer trials use a surrogate measure of tumor shrinkage. Ideally, both would be taken into consideration.

Darrow and his research associates studied FDA approvals, changes in the law and regulations, and how the industry funds agency reviews from 1983 through 2018. They found that the average number of new drug approvals annually grew from 34 in the 1990s to 41 in the 2010s. In the 2000s, it dropped to 25 a year. But now they are increasing. For example, in 2019, the FDA approved 48 new molecular entities and new therapeutic biological products. That doesn’t include vaccines, allergenic products, blood and blood products, plasma derivatives, cellular and gene therapy products, or the numerous new indications approved for existing therapies.

Darrow, with Jerry Avorn and Aaron S. Kesselheim, both with the Division of Pharmacoepidemiology & Pharmacoeconomics at Brigham & Women’s Hospital, found that faster approvals were related to legislative and regulatory modifications that started in the 1980s. Although there are probably several reasons for those changes beginning in that period, much of it is likely related to the beginning of the HIV epidemic and demands from patient populations and advocates to fund more research and get therapies–any therapies—to market faster.

Just some of those regulations include: the 21st Century Cures Act (2016), which authorized funds for the Precision Medicine Initiative and Cancer Moonshot; the Biologics Price Competition and Innovation Act (BPCIA, 2010), creating an abbreviated pathway for follow-on biologic products; Breakthrough Therapy designation (2012), for drugs that showed substantial improvement over existing therapies; the Hatch-Waxman Act (1984), which created an Abbreviated New Drug Application pathway for drugs approved after 1962; and the Pediatric Research Equity Act (2003), which required results from pediatric assessments to be submitted as part of New Drug Applications (NDAs).

Congress also passed the Prescription Drug User Fee Act in 1993, and that first year, FDA collected $29 million in fees. In 2018, the agency brought in $908 million in PDUFA fees. Or, as the study notes, industry fees were responsible for about 80% of the money spent on FDA employee salaries for drug reviews.

“There is some concern about the incentives that this created within the FDA,” Darrow told NPR. “And whether it has created a culture in the FDA where the primary client is no longer viewed as the patient, but as the industry.”

Another factor that is related, is the concept of me-too drugs. These are basically drugs that are very structurally similar to approved drugs, with only minor differences. That’s not necessarily a bad thing, because they need to be at least as good as the drugs already on the market, and generally need to be better—although not necessarily by much. Which does mean a number of companies spend time on developing drugs that are only incrementally better than others on the market.

Joshua Sharfstein, former FDA Principal Deputy Commissioner, told NPR that there are more changes needed to ensure drugs are worthwhile for patients. “Some of them are really great, and some of them [are] not so great. And a lot of them are very expensive.”

Sharfstein is currently a professor at the Johns Hopkins Bloomberg School of Public Health. He wrote an editorial in JAMA that accompanied the newer study. In it, he suggests it’s time to reevaluate the FDA’s expedited approval programs to determine which ones are working and which ones are increasing healthcare costs.

“We’ve kind of reached a point where it makes sense to pause and see whether we can do things better,” Sharfstein said. “And I think we can.”

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