Congress gave the Food and Drug Administration more power to hold drugmakers accountable under the gigantic spending bill that became law in December 2022.
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Sarah Silbiger/Getty Images
Congress gave the Food and Drug Administration more power to hold drugmakers accountable under the gigantic spending bill that became law in December 2022.
Sarah Silbiger/Getty Images
The massive spending bill that became law last December also included fixes to a problem that has haunted the Food and Drug Administration for years.
Drugmakers could get quick approval for some drugs — with preliminary data — on the promise that they would do more research after the fact to make sure the drugs worked. But companies have often been slow to follow up on these so-called fast-track approvals, leaving patients uncertain about their drugs.
COVID-19 vaccines have not received this type of approval. But the FDA has given fast-track approvals to more than 100 drugs aimed at treating cancer, HIV, premature birth and other conditions over the past three decades.
Among other things, the new law gives the FDA more leverage to hold drug companies accountable for their promises about continued research. Now, for example, the agency has the explicit power to require drugmakers to have started confirmatory studies as a condition of fast-track approval.
“It basically strengthens their hand,” says Robin Feldman, a professor at the University of California San Francisco School of Law. “However, just because the FDA has the power doesn’t mean they’re going to use it.”
The FDA wouldn’t say if it’s doing anything different on fast-track approvals, other than that it’s working on a plan. “The FDA will implement these new authorities and provide updates as appropriate,” an agency spokesperson said in a written statement.
Why fast-track drug approvals are controversial
Critics of the program crescendo after the controversial accelerated approval of Alzheimer’s drug Aduhelm in 2021. The maker of Aduhelm initially priced it at $56,000 per year, even though the FDA approved it because of its ability to remove sticky amyloid plaques from the brain with no evidence that removing the plaque could slow the process. loss of mental abilities of patients. The drug failed, with insurers refusing to cover it, and the drugmaker, Biogen, had to lower its price.
Dr. Aaron Kesselheimprofessor of medicine at Brigham and Women’s Hospital and Harvard Medical School, resigned from an FDA advisory board over Aduhelm’s endorsement.
His research revealed flaws in the fast-track approval program, including the fact that only 1 in 5 cancer drugs with accelerated approval “demonstrated improvements in overall patient survival.”
A NPR survey last year found that many of the promised confirmatory studies are delayed, leaving doctors and patients in the dark for years about whether the drugs really work. Specifically, NPR found that 42% of ongoing confirmatory drug studies required after expedited approval took more than a year to start or did not start at all.
Meanwhile, drugmakers were more likely to repeatedly raise the price of drugs with fast-track approvals compared to drugs with traditional approvals.
In September, the Office of Inspector General of the Department of Health and Human Services released a report on the backlog of confirmatory studies for drugs whose approvals have been expedited. The report’s findings were consistent with those of the NPR.
During NPR’s investigation, a reporter asked the agency about the timeline for the confirmatory study. Dr Jacqueline Corrigan-Curay, senior deputy center director of the FDA’s Center for Drug Evaluation and Research, said the agency would still like to have those confirmatory studies underway at the time of expedited approval. But there are no regulatory requirements, she said.
“If you have the data and it responds to an expedited approval and there is this unmet medical need, we have to move forward” with the approval, she said at the time.
However, according to the FDA’s former senior deputy commissioner for food and drug Dr. Rachel Sherman, the agency has always had the power to require that confirmatory studies be underway at the time of approval, but has not often exercised it.
“I’ve never lost an argument with a company,” she says of her three decades with the agency. “Sometimes they convinced me they were right and I was wrong. But if I wanted something, I got it. Because at the end of the day, the FDA has – what’s the right word ? – a pulpit of intimidation.”
Feldman of the University of California says the new law can be helpful if a drug company tries to push back against an FDA decision.
There have been times when the FDA has had powers but neglected to use them, Feldman says, pointing to a recent study in JAMA about the fact that 3,000 clinical trials had failed to report results between 2017 and 2021, but the FDA only submitted notices of non-compliance to 58 of them.
The agency also tried to put its foot down, was sued by drugmakers, and lost. That’s what happened when he tried not give benefits to rare disease drugs makers of a chemotherapy drug called Bendeka. The drug maker sued and the FDA lost.
The new legislation, at least, should provide clarity.
Congress Passed a Fix – But It Almost Didn’t Happen
Congress passed legislation to address long-standing issues with fast-track approval in December, but that almost didn’t happen.
Several bills have passed through Capitol Hill over the past year to reform fast-track approvals.
The changes were to be incorporated into the renewal of the Prescription Drug User Fees Act in September, but Congress passed it without any amendments. who was worried Dr. Reshma Ramachandran, of Yale Medical Schoolwho was one of the doctors who traveled to Washington, DC, to speak to lawmakers about expedited approval updates.
“We really wanted to make sure they would deliver on their commitment to review these reforms as part of the end-of-year spending plan,” she said, adding that the “breathtaking” public meetings around the withdrawal of the le drug Makena (which was prescribed in hopes of preventing premature births) seemed to push Congress into action.
Following confirmatory studies that failed to prove Makena’s effectiveness, the FDA’s Center for Drug Evaluation and Research recommended removing the drug from the market in October 2020. But as the drugmaker does not has not voluntarily withdrawn the drug, a hearing to discuss the potential withdrawal of Makena has been required. It took two years for the FDA advisory committee to meet, and members voted to take it off the market. The FDA has not yet withdrawn the drug’s approval, however.
“The FDA was trying to pull back a drug that had failed — not just a confirmatory trial, but several other studies,” Ramachandran says. “I think that really spurred members of Congress, but also the FDA, to really say, ‘Hey, we need these common sense reforms. “
FDA powers are discretionary, not mandatory
Changes to the expedited approval process were finally passed into the omnibus year-end spending bill that was signed into law Dec. 29. The new law includes several fixes, including one that allows the FDA to require companies to begin confirmatory studies. Before the agency grants expedited approval to the drug.
“We wanted this to be codified in legislation so that it would not be an exception. It would just be the rule,” Ramachandran said. “When this happens, it avoids significant delays in starting trials, but also in completing trials.”
Yet the law does not categorically require that studies confirming a drug’s effectiveness be underway at the time of approval. He only says that FDA officials “could demand it.”
“So generally these are discretionary rather than mandatory,” says Feldman of the University of California. “In other words, it allows the FDA to do things, but doesn’t force the FDA to do things. So that’s a big difference.”
The law may make it easier for the agency to remove a drug from the market if studies show the drug is not effective.
“When a drug receives expedited approval and that confirmatory study fails, that’s really an important finding that indicates that drug doesn’t have the same level of efficacy that we expect from other approved drugs,” says Harvard’s Kesselheim. “And there’s no reason for this drug to stay on the market at this point.”
Additionally, the law creates new transparency requirements and advice to ensure that everyone at the FDA is on the same page about how this type of approval should be used.
The rules may therefore need to be tightened again in the future.
“The final language was not [as] …as airtight as possible,” Kesselheim said. “So I think there’s some wiggle room.”