Once a drug reaches store shelves, it’s safe … right?
In a new , researchers concluded that safety issues are detected in nearly a third of drugs after they are approved by the Food and Drug Administration (FDA).
The findings of the Yale-led study were published last week in the Journal of the American Medical Association (JAMA).
While drugs are rigorously tested for years before approval, these trials typically focus on a small number of patients.
Once the drugs are made available to larger numbers of people, issues will invariably pop up, the researchers said.
The findings might sound alarming, but researchers and experts interviewed by Healthline say this means the FDA is doing its job by continuing to monitor drugs after they’re approved.
Post-approval is the ultimate test
There are a lot of facets to the drug approval process.
“The FDA’s approval process involves a balance of clinical benefit against unnecessary or undesired outcomes in the form of adverse events,” Jeff Patrick, PharmD, director of the Drug Development Institute at The Ohio State University Comprehensive Cancer Center, told Healthline.
“Safety is extremely important to the FDA,” he added. “They have to balance the clinical benefit of the patient who needs therapy against the risk that any given drug might pose, and really seek to navigate that balance.”
Still, though, no specific number of clinical trials can predict how a drug will be received by the general population.
“FDA approval does not mean that we know everything about a drug,” Dr. Nicholas Downing, first author of the research paper, and resident physician of internal medicine at the Brigham and Women’s Hospital in Boston, told Healthline.
“When a drug’s approved, there’s lots that we don’t know,” he explained. “We don’t know if the drug is going to be as safe, or perhaps not as safe, as the FDA thought it would be on the basis of premarket clinical evidence. We don’t know if the drug is going to be as effective as the FDA thought it would be on the basis of premarket clinical evidence. So there is inherently some uncertainty that is there at the time of approval. And as drugs are used for longer periods of time, and in broader populations, sometimes we learn new information.”
Patrick points out that there can never be a one-size-fits-all approach when it comes to treating patients with drugs, as different people can respond in different ways.
“You don’t know what can happen to any given patient until you expose the patient to that particular situation,” he said. “Our mantra here at OSU Comprehensive Cancer Center is ‘there is no routine cancer,’ and we mean that. Because every patient can respond to therapies differently depending on their genetic profile or the severity of the disease, or so many other factors.”
FDA taking its role seriously
The fact that 32 percent of drugs are flagged after being approved actually means the FDA is doing its job, experts said.
“The fact that a post-market safety event has been detected for 1 in 3 drugs tells me that the FDA is looking for these issues, and that’s important,” says Downing. “It tells me that the FDA doesn’t feel that its responsibility ends at the time of drug approval. It tells me that the FDA is taking its responsibility for ensuring the safety of drugs throughout their entire life cycle very seriously.”
“If there were no events, or there were very few events, you’ve got to ask the question of whether the FDA is even looking for these things,” he added.
“If they didn’t monitor these drugs post-approval, there would be a shift toward, perhaps, a relaxed platform where safety might not be taken so seriously,” he said.
Downing points out that continual monitoring and testing can yield new insights on drugs that have been in the marketplace for decades.
“We’re still doing clinical trials on aspirin today,” he noted. “That’s one of the older medicines that we have, yet we’re still finding new ways to use the drug, and we’re still learning about it.”
The new research was based on earlier work by the same team.
Downing says there are still insights they’d like to tease out.
“On average, these post-market safety events occurred 4.2 years after approval,” he said. “One question you might ask: Is there a way to identify drugs that might have safety problems sooner? Such that you minimize the number of people or the amount of time that people are taking a new drug before a new safety event comes to light,” he said. “I wonder if there are ways and methods we could use to study the safety of drugs that would enable us to identify post-market safety events quickly, or in a shorter period of time than 4.2 years.”
While 32 percent of drugs were found to have post-market safety events, both Downing and Patrick wonder if this is the right number.
“Frankly, I’m surprised it’s only a third,” Patrick said. “I’d consider it a relatively low number.”
Downing echoes this.
“Is 1 in 3 the right number? Is it too high, too low, or just right?” he asked. “I don’t know, but what it does tell me is that we’re looking for these things and we’re finding them. These post-market safety events happen, and they reflect the fact that there are things we don’t know about new drugs when they’re approved, and we learn about them when they’re used in bigger populations for longer periods of time.”