FDA chief Rob Califf: The business of health is booming but people's outcomes aren't improving
While referring to himself as living in the proverbial “overtime” of life at the age of 70, newly Senate-confirmed FDA chief Rob Califf said his hope, at the end of his second run at the agency, is to leave the system in a way that enables people to better find out the truth about the risks and benefits of products the FDA regulates.
The famed clinical trialist from Duke, who also recently spent time at Google’s parent company Alphabet, made clear that his vision is to fairly evaluate the real value and worth of new products, and to quickly dispose of investigational products that aren’t useful.
“We do not have that system now,” Califf said, although he said compared to “where we were, we have a great system.”
On the part not done as well in the US vs. the rest of the world, Califf pointed to the fact that the US is one of the greatest inventors in the world but in last place for life expectancy among other high-income countries.
“I’m in love with the term sub-optimization,” Califf said, defining the term as a system with many parts that are incentivized to optimize their own well-being, but the system as a whole is less than the sum of the parts.
“I think that is an American problem right now,” he said referring to sub-optimization, noting that the business of health care has never been better but the outcomes of the people the system is trying to serve are not doing better.
On his promises to Congress regarding accelerated approval reforms, Califf told Matt Herper at a STAT News event Thursday that “the amount of heat generated in the discussion is inversely proportional to quality of the studies done.”
He also made clear that he doesn’t think it’s within the role of the FDA commissioner, as a political appointee, to make decisions on specific products (although this interpretation has been disputed, as was the case with his decision to approve Sarepta’s DMD drug eteplirsen). The people who make the decisions on products are full-time civil servants who have no conflicts of interests, he noted, and it’s their job to make these approval decisions.
“My job is to make sure what the rules are of the game, and the interaction with the outside world, and looking across at systematic policies that would improve things,” he said.
In the cases mentioned, he said, referring to the recent ALS drug that went before an adcomm earlier this week and Biogen’s controversial Alzheimer’s drug, “there were real imperfections in the way the studies were done that make it hard.” Patients who need therapies desperately need to be sure the studies actually answer the question relevant to their needs, he added.
While noting that the definition of an accelerated approval is that an investigational drug is “reasonably likely” that an unvalidated surrogate would lead to clinical benefit, he explained that the pathway does lead lots of companies to get into surrogate endpoints, which might not necessarily be a lower quality study, but it’s a different study.
But he said he thought it’s usually naïve companies that are going after these unvalidated surrogates with lower-quality studies, rather than companies trying to get away with less clinical work.
So how to improve the system for accelerated approvals?
“I think you’re aware there’s consideration of improvements currently,” he said, referring to FDA’s legislative proposals. “It’s that space in between the approval and the final determination of clinical risks/benefits. Right now the system is painfully slow to get good answers. Regulatory science studies have come to different conclusions, but essentially we need to get good studies done after the approval in a very efficient way, as quickly as possible.”
On the topic of FDA-CMS relations, which have been a point of interest in recent months as CMS has so far balked at covering Aduhelm widely, Califf called for “a smooth hand-off from FDA to CMS,” as the two “need to coordinate so CMS is equipped to make the right decision.”
In the lead up to his Senate confirmation, Califf previously discussed the need for confirmatory trials to speed up after these accelerated OKs. Comparing the accelerated pathway to a relay race, Califf argued the “FDA runs the first lap, gets to the end, drops the baton down on the ground, and someone else like CMS has to figure out where the baton is, pick it up and start all over.”
A question from the audience at the Stat event also asked Califf if he might release the agency’s complete response letters, or rejections to pharma companies, a move Califf’s predecessor Scott Gottlieb vowed to do but didn’t.
“The complete response letters — there aren’t that many of them,” Califf said, while noting that he’s not opposed to releasing them, it’s “not as big of a deal as many people make it.” Bad applications get weeded out more frequently now earlier in the approval process, and the CRLs often have to do with manufacturing issues, which are redacted, he said.
“One of the many things I want to work on is misinformation,” Califf said. “I want to be very proactive.”
