Nearly a third of drugs approved for sale by the U.S. Food and Drug Administration (FDA) between 2001 and 2010 were affected by major safety issues only identified after being available to patients, according to a new study released Tuesday.
The May 9 report in the Journal of the American Medical Association analyzed the 222 drugs approved by the FDA in the 10-year timeframe and found that 71 (32 percent) of those drugs were affected by postmarket safety events over years of follow-ups. Three were removed from the market, 61 received black-box warnings and 59 were the subject of safety communications.
Researchers at Yale University said the findings underscored the need to monitor new drugs for years after they have been available on the market.
“We seem to have decided as a society that we want drugs reviewed faster,” lead author Joseph Ross told The Washington Post. That makes it critically important “that we have a strong system in place to continually evaluate drugs and to communicate new safety concerns quickly and effectively,” he said.
The study found that issues did not come to light until a median of 4.2 years had passed.
Drug Clinical Trials Don’t Always Tell Full Picture
The FDA requires evidence that a drug is safe and effective to be approved for the market. However, the study says that some clinical trials use a relatively small amount of patients with short follow-ups.
“No drug is completely safe, and during premarket evaluation, we are not going to pick up all the safety signals,” said Ross, according to The San Diego Union-Tribune.
Dr. Eric Topol, a cardiologist-geneticist who was not involved in the study, said that the results were not surprising but were troubling. He cited clinical trials that use certain patients to produce favorable results as part of the problem.
“Usually those clinical trials are relatively small, and they are not representative of the real world of patients, with multiple medical conditions and variable age, and all other things that you don’t capture in a clinical trial,” Topol told the Union-Tribune. “Clinical trials have inclusion and exclusion criteria — it’s a contrived setting. And then, when the drug is put out in the real world, with mass quantities of exposure, all of a sudden you find things that you never saw before.”
Conditional approval with a probationary period would likely be a safer way to detect problems, Topol suggested.
FDA Under Pressure for Quicker Approval
President Donald Trump has said he wants the FDA to start speeding up the approval of drugs that treat life-threatening injuries and called the current process “slow and burdensome,” according to Stat News.
“While the administration pushes for less regulation and faster approvals, those decisions have consequences,” Ross said to NPR.
Some drugs are allowed to pass through an accelerated approval process, but those were found to have a higher incidence of safety events. Those types of approvals usually use surrogate endpoints to offer evidence of safety or effectiveness. This means other things besides survival are measured, such as tumor size.
“This [finding on surrogate endpoints] has the greatest relationship to policy today,” Ross said. “In the 21st Century Cures Act, there’s a push to have the FDA move to further support the use of surrogate markers … [but] they’re more likely to have concerns in the post-market setting.”
The 21st Century Cures Act was the last piece of significant legislation signed into law by President Barack Obama and offers new ways to expedite the approval process of the FDA. Some say it could help pass through poorly tested drugs.
“I’m actually sympathetic to the idea that there are ways in which the FDA can be more streamlined and do a quicker job,” Dr. Vinay Prasad, a hematologist-oncologist and professor at Oregon Health and Sciences University, told NPR. “The one place you don’t want to cut a corner is safety and efficacy prior to coming to market.”
FDA Good at Catching Issues After Approval, Author Says
Even though the safety concerns were concerning, Ross said that the FDA was doing a “great job” analyzing drugs after they were approved.
“We know that safety concerns, new ones, are going to be identified once a drug is used in a wider population. That’s just how it is,” Ross said to the Los Angeles Times. “The fact that that’s such a high number means the FDA is working hard to evaluate drugs, and once concerns are identified, they’re communicating them.”
The FDA revealed that it is reviewing the findings of the study and performs regular postmarket monitoring.
“In general, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health,” FDA spokeswoman Angela Hoague told Kaiser Health News.
The study may also have an impact on how pharmaceutical companies evaluate the safety of drugs before and after they make it to market.
A spokeswoman for the Pharmaceutical Research and Manufacturers of America, a trade group representing pharmaceutical companies, told the Los Angeles Times that the group was reviewing the study and remains committed to postmarket surveillance of new medicines.
“Even with rigorous clinical studies and regulatory review it may be impossible to detect certain safety signals until several years after approval, once the medicine is in broader use,” spokeswoman Holly Campbell said.