FDA Commissioner Robert Califf, M.D., didn’t mince words when recently asked how the U.S. fared in terms of generating evidence for medical products.
“I mean by my standards, it’s not even good. I’d say mediocre at this point,” he said at a roundtable with the Alliance for a Stronger FDA, a lobbying group that advocates for agency funding. Califf said the U.S. does a good job developing medical products through early-phase development before hitting a wall.
“You ask the question: Do we understand what the right doses of drugs are? How to use devices? How to combine and compare choices that we have to make with medical products? I’d say we’re doing a lousy job of generating that evidence,” he said.
Califf punctuated his comments by noting how more drug developers are taking the accelerated approval pathway to nab approval, a process originally launched in the early '90s to invigorate development of HIV drugs. If new medicines fulfill an unmeet need, they can score accelerated approval with biomarker data rather than proving a clinical benefit so long as the companies can prove a clinical benefit in a follow-up trial (also known as “confirmatory” trial). Now, it’s commonly used to expedite the launch of new cancer drugs.
But it was the recent accelerated approval of Biogen’s Aduhelm, a treatment for Alzheimer’s disease, that Califf called out explicitly, saying the nine-year timeline to complete the follow-up trial was a “signal” to the larger medical product community. That June 2021 decision was made prior to his tenure at the agency.
“People said, ‘Wait a minute, that doesn’t sound like the time frame that’s reasonable,’” he said, adding that the current system to generate evidence in these postmarket studies is “simply inadequate.”
One of the reforms floated by Califf himself has been to start confirmatory trials before companies receive approval in an effort to boost enrollment. Paul Hastings, chairman of the Biotechnology Innovation Organization, a biopharma trade organization, told Fierce Biotech that proposal would slow down patients’ access to therapy.
Califf also highlighted the U.S.’ reliance on Israel for COVID vaccine-related data, which have consistently informed the FDA’s guidance on booster administration, including the latest decision to authorize a fourth dose.
“We just didn’t have the data in the U.S. to inform that decision. We got to do better.”
Califf's solution to the data generation issue is broader, suggesting Americans’ electronic health records could be better utilized to “do studies very inexpensively.” But he was clear that the lack of evidence has left U.S. clinicians and regulators at a disadvantage.
“‘Good’ would look like every time there’s a medical product we would understand the benefits and risks and how the product should be used in practice so that the labels were actually informative to the people that have to make the decisions,” he said.