A special Food and Drug Administration process to get patients earlier access to new drugs has come under fire.
The accelerated approval process speeds medicines to market based on preliminary study data. But there's a condition: The drugmaker needs to do an additional study after the drug is on the market to prove the drug really works. If the study doesn't pan out, the drug can be pulled off the market.
But some drugmakers have fallen behind on their commitments to do those confirmatory studies, leaving patients and their doctors to make difficult decisions with incomplete information.
"The promise of accelerated approval is that you're going to get access and answers," said Gregg Gonsalves, a Yale professor. "And what happens is you got the drugs on the market, but you didn't find out if they worked."
NPR examined 30 years of government data and records and conducted dozens of interviews as part of its investigation. Here are 5 takeaways.
Companies are slow to start the follow-up studies they promised the FDA
NPR found that 42% of currently outstanding confirmatory studies – or 50 of them – either took more than a year to begin following accelerated approval or hadn't started at all. Nineteen of those required studies still haven't started three years or more after accelerated approval. Four of them haven't started more than 10 years later.
That means many drugs that made it to market with an accelerated approval are being used – sometimes for years – without patients, doctors or regulators knowing if they really work.
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Drugs with accelerated approvals have more price hikes
While companies making drugs with accelerated approvals drag their feet to start confirmatory studies, they are also more likely to increase the prices of those drugs, according to GoodRx, a website that helps patients get discounts on drugs.
GoodRx conducted a pricing analysis at NPR's request and found that, on average, drugs granted accelerated approval have 26% more price increases over 10 years than other medicines.
Gonsalves likened this to "tapping the brakes" on confirmatory studies while "pressing the accelerator" on price. "It doesn't surprise me that they're trying to ratchet up the ability to reap profits. At the same time, they're sort of sluggish in their statutory duty to provide timely initiation and completion of studies."
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It can be hard to tell if a drug got an accelerated approval
The FDA team reviewing antiretroviral drugs to treat HIV, which accounted for about half of all accelerated approvals in the 1990s, added special warnings to the drug labels in bold, black boxes if the approvals were accelerated.
"We were approving them so fast that there was no literature for doctors to look at," said Dr. Rachel Sherman, who was working in the FDA's Center for Drug Evaluation and Research at the time. Doctors didn't know what an accelerated approval was, so her team wanted to make sure it was clear that the decisions relied solely on preliminary data.
There's no regulation requiring this prominent kind of disclosure and no agency-wide policy mandating it either. "Now, you won't see that anymore," she said of the special warnings.
Accelerated approvals are becoming more common
For the first two decades that accelerated approval was an option, the FDA granted only a few each year. After a 2012 law formalized the agency's policy, the approvals boomed.
In 1992, there was just one accelerated approval. But in 2020, there were 49, according to NPR's analysis. Twenty-eight of those 2020 accelerated approvals were for new drugs, and the rest were for expanded uses of existing medicines.
Today, there are around 200 drugs with accelerated approvals. But now, many of them have more than one use that got this fast track, especially if the drugs treat cancer.
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As criticism grows, change might be coming
Criticism of the accelerated approval process has mounted as the number of drugs being sold without completed confirmatory studies has grown. The issue threatened the Senate confirmation of Dr. Robert Califf as FDA commissioner earlier this year.
"Some companies have taken advantage of the Accelerated Approval Pathway, falling behind on providing confirmatory evidence, while FDA has shied away from using its authority to hold drug companies accountable for fulfilling their obligations," Sen. Ron Wyden, D-Ore., wrote to Califf.
Wyden asked how the agency would hold companies accountable for failing to complete required confirmatory trials under accelerated approval. Acknowledging the problem, Califf wrote back, "it is incumbent upon the FDA to ensure that the work does not end with the initial approval."
Penalizing companies that don't meet accelerated approval requirements is on the FDA's list of planned guidance documents for 2022. The agency's 2023 budget document includes legislative proposals that would give the FDA more power to solve the problem of tardy trials.
You can contact NPR pharmaceuticals correspondent Sydney Lupkin at slupkin@npr.org.
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