Managing Health Risk: The Impact of the Accelerated Approval Integrity Act on Covid-19 and Other Anticovirvirino Diseases
I can understand the argument, on an emotional level, that when it comes to your body and life, you should be able to assume whatever risk you want. There’s also the compelling argument that in certain situations, whether it’s a pandemic affecting millions or a rare, devastating disease, there should be a lower bar for evidence and a greater willingness to allow people to assume risk. When the F.D.A. granted its emergency use authorization for the Covid-19 vaccines, they did so with a view to avoiding absolute certainty about a product’s safety or efficacy. Relief in a crisis can be provided by regulatory flexibility.
The desire of patients to use unproven medical treatments amid harrowing illness is unlikely to abate. However, access at the expense of collecting essential data is not a win for patients. Accelerated approval provides a reasonable model, but the guardrails have so far been largely theoretical. Only with changes can the promise of this program be truly met.
A bill introduced in the House in March, the Accelerated Approval Integrity Act, aims to address the deficiencies while preserving the benefits of accelerated approval. Drug companies will need to enter into an agreement with the F.D.A. before they get accelerated approval of their drugs. It would mandate more frequent updates from follow-up studies, automatically expire accelerated approval one year after the agreed-upon deadline for further study and streamline the process for taking ineffective products off the market.
Adding rigor to the process will go a long way in making it easier for clinicians, patients and insurers to have more faith in the system.
The COVID-19 vaccines weren’t granted this kind of approval. But the FDA has given accelerated approvals to more than 100 drugs aimed at treating cancer, HIV, preterm birth and other conditions over the last three decades.
Among other things, the new law gives the FDA more leverage to hold drug companies accountable for their promises about further research. As far as the agency is aware, it can require drugmakers to have begun confirmatory studies as a condition of accelerated approval.
“This essentially strengthens their hand,” says Robin Feldman, a professor at the University of California College of the Law, San Francisco. “However, just because the FDA has the power doesn’t mean it’s going to use it.”
Criticism of the program crescendoed following the controversial accelerated approval of Alzheimer’s drug Aduhelm in 2021. The FDA approved Aduhelm for its ability to remove sticky brain plaques without proof that they could slow down patients’ cognitive decline, but the manufacturer set a price of over $60,000 a year. The drug flopped, with insurers refusing to cover it, and the drugmaker, Biogen, had to lower its price.
Dr. Aaron Kesselheim, a professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, resigned from an FDA advisory committee because of the Aduhelm approval.
Only 1 in 5 cancer drugs that were granted accelerated approval demonstrated improvements in overall patient survival, according to his research.
Meanwhile, drugmakers were more likely to repeatedly hike the price of drugs granted accelerated approval compared with drugs granted traditional approval.
The Inspector General for the Department of Health and Human Services has an office that deals with delinquent confirmatory studies. The report’s findings were consistent with NPR’s.
According to the former FDA principal deputy commissioner, Rachel Sherman, the agency had the power to require that studies be underway at the time of approval but didn’t often do it.
She said that if the data was good and there was unmet medical need, it would be good to go ahead with the approval.
“I never lost an argument with a company,” she says of her three decades with the agency. They sometimes convinced me they were right and I was wrong. If I asked for something, I got it. The FDA can be called a bully pulpit at the end of the day.
According to a recent study published in the Journal of American Medical Sciences, there were times when the FDA failed to use its powers, such as when the FDA only submitted notices of noncompliance to 58 of the 3,000 trials.
The agency has had to put its foot in it’s mouth, being sued by drugmakers and losing. That’s what happened when it tried not to give rare disease drug perks to the makers of a chemotherapy drug called Bendeka. The drug’s manufacturer sued, and the FDA lost.
Changes were expected to get folded into renewal of the Prescription Drug User Fee Act in September, but Congress passed it without any riders. That worried Dr. Reshma Ramachandran, of Yale School of Medicine, who was one of the doctors who traveled to Washington, D.C., to talk to legislators about accelerated approval updates.
She said that they wanted to make sure that they were going to hold onto their commitment to revisit the reforms, as part of the end-of- year spending package.
“The FDA was experiencing trying to withdraw a drug which had failed — not just a confirmatory trial, but multiple other studies,” says Ramachandran. “I think that really gave cause to members of Congress, but also the FDA, to really say, ‘Hey, we need to have these common sense reforms.’ “
We wanted legislation to codify that so it wouldn’t be an exception. “That would be the rule and it would be up to you.” “When that happens, there’s more time for starting the trials, but also time for completing the trials.”
“So generally these are discretionary rather than mandatory,” says University of California’s Feldman. It doesn’t require the FDA to do things, but it allows them to do things. So that’s a big difference.”