FDA Flap
A new study published in JAMA, the journal of the American Medical Association, claims that the US Food & Drug Administration (FDA) is approving new drugs faster and using less rigorous standards to see if the drugs are effective, according to an article by Meera Jagannathan in Market Watch.
Jonathan Darrow, lead author of the study and faculty member at Harvard Medical School, said there was “an erosion of evidence standards at the FDA,” as FDA programs tried to accelerate drug development. He claimed that, “‘There has been an accumulation of special FDA programs over the past 40 years that reduced the amount and the quality of the evidence that’s required for drug approval. The FDA has increasingly accepted less data and more surrogate measures and has shortened its review times, allowing some attributes of clinical evidence to be more flexible over time.”
The researchers — including coauthors Aaron Kesselheim and Jerry Avorn, professors of medicine at Harvard Medical School — looked at FDA databases of approved new drugs and FDA drug-approval programs. Some of them were designed to get life-saving drugs to patients faster. They also examined user fees that drug manufacturers pay to help fund FDA activities. The study determined that the share of new drug approvals backed by at least two “pivotal trials” declined from 81 percent in 1995–1997 to 53 percent in 2015–2017. These randomized clinical trials are supposed to determine whether a drug is effective and safe for humans.
The study also found that the FDA was relying more on “surrogate” measures to predict actual clinical benefit and that the median review time for standard and priority drug applications decreased significantly from 2.8 years three decades ago to 10 months in 2018. Still, there was little movement in overall drug-development time, possibly because of factors such as an increase in application submissions for rare-disease drugs or “longer time horizons needed to establish efficacy,” the authors said. “These regulatory innovations have not clearly led to an increase in new drug approvals or to reduced total development times,” they claimed.
Another finding of the study was that annual fees paid to the FDA by the pharmaceutical industry, authorized by Congress in 1992 to raise money to speed up review times, had increased from $29 million in 1993 to $908 million in 2018. About 80 percent of drug-review personnel’s salaries are derived from these fees.
An FDA spokesman responded that “Based on a preliminary analysis, the FDA is concerned that the publication’s researchers do not adequately consider the marked changes in the types of drugs that the FDA now reviews and the patient populations targeted by development programs compared to those from 10 to 20 years ago, nor the type, quality, and extent of data the FDA routinely receives now compared to decades ago as is referenced in the publication.”
He continued, “For example, statistics used in the study that compare FDA actions on applications from recent years (such as the overall first cycle approval rate, or how many trials the FDA reviewed in an application, or use of surrogate endpoints) relative to actions decades ago, without considering these important factors, are potentially confounded and could result in inaccurate conclusions.”
The FDA is conducting a detailed review of the JAMA article and its recommendations. It will provide a more comprehensive response after analyzing the publication.
The article suggested ways to be a smart consumer of prescription drugs. Patients should consider more than that cost of the drug price, look for risks and benefits, ask about similar drugs and find out if the prescribing doctor has a relationship with the manufacturer.
