Former Food and Drug Administration Commissioner Robert Califf was in Silicon Valley to receive an award from The Precision Medicine World Conference on Wednesday. In a fireside chat, Califf, a cardiologist by training, addressed a range of issues from whether precision medicine has advanced enough to how he would advise his successor at the FDA.
Prepare for DelaysThe FDA, like other agencies, is being reviewed by the Trump administration to weed out what they believe federal agencies have: inefficiency and worker redundancy. This effort may shrink the agency through buyouts — the legality of which is in doubt — or layoffs and that workforce reduction might affect timelines of products submitted for regulatory approval to the agency.
“To do the work, you actually have to pay people and they have to exist. So if enough people leave FDA, it doesn’t matter what the law says, you’re still going to have delays. Remember the user fees came into existence because the FDA couldn’t meet the timelines. And I would personally love it if the taxpayer paid the fair share and we didn’t have companies paying for [regulatory] activity. On the other hand, user fees on the medical product side have made an enormous difference. It is like a business. The evaluation is done by civil servants, not by political appointees, but it’s done on a timeline and those metrics are watched just like you would watch any other business. But if the infrastructure of FDA is gutted, it won’t be possible to meet those timelines.”
Earlier in his on-stage interview, Califf, who has worked in the private sector at companies like Alphabet, took offence at how federal workers are being portrayed.
“I think the people that are attracted [to the FDA] are very hardworking people and also have to say, having worked in all sectors, the idea that federal employees are lazy or not as good as other employees is just flat out wrong,” he said. “But that is the rhetoric that’s going on right now.”
He recalled how his career at the FDA began as a deputy commissioner for medical products and tobacco.
“Despite all the vilification that’s going on right now of federal employees, it’s an amazing experience where your mission is the public health; it’s the entire American public,” he said.
Abbott’s Really “Screwed this One Up”
Califf was asked about the lessons he learned in handling the infant formula shortage and he explained how the infant formula industry was hyper-concentrated among a couple of players, including Abbott.
“The industrial base for manufacturing the formula was hyper-concentrated in a small number of plants that were, let’s just say out of date,” he said. “And so when chronobacter [sakazakii] was going all over the plant making it into [the infant] formula of Abbot — and I say this as a cardiologist, I’ve used a lot of Abbott products, it’s a good company it makes a lot of good products — they really screwed this one up and the recall was necessary because you can’t send out bacteria-contaminated formula to half of infants or more [that] are heavy uses of formula for a whole variety of reasons in the United States. The shelves were bare and it was a very difficult situation.”
Later however, the company cooperated and the agency began co-manging the company’s operations tied to infant formula as part of a consent decree.
But the FDA wasn’t blame-free either. Califf said that there was a structural problem at the agency where the food side was not good at decision making. So a structural reorganization ensued.
“We had to undergo the biggest reorganization in the history of the FDA that happened during my tenure affecting [many thousands of] employees to create a structure that can make decisions better,” he said.
FDA’s Focus on Nutrition is Severely LackingAfter the reorganization of the food side of the agency, there are three components within it: people who deal with food safety with regard to microbiologic and viral contaminants of food; people who deal with checmical safety and nutrition.
The food safety happens to be the” vast majority” of what’s funded at the FDA followed by chemical safety and there’s nutrition.
“Chemical safety and nutrition at the FDA have been dramatically underfunded,” Califf said. “And nutrition is really a sad thing because we all think nutrition should be better. But there are only a couple of dozen people at FDA who are paid to work on nutrition.”
What Worries Califf the Most about Artificial Intelligence
Califf is not worried about the pre-market aspect of artificial intelligence and the FDA has already shared guidelines for best practices. It’s what happens after the products are deployed in the real world
“Health systems are the biggest issue here because as we get more and more into generative AI, the algorithms, if you put them in place, they’re going to change and you don’t know whether you’re going to drift in a better or worse direction unless you measure it. So there’s a term — local recurrent validation — which basically means the algorithms have to be validated as close to continuously as possible in the environment in which they’re deployed,” Califf explained. “The only people that can do that are the people that are deploying them. That’s our health systems. I don’t know of a single health system in the US today that has the tools that it needs to do this, but it’s not like it’s a secret.”
He Wasn’t Optimistic about Precision Medicine’s Future and It’s Been That BadAn audience member asked how Califf would evaluate how precision medicine has evolved in the past decade. The answer wasn’t pretty.
“I was not very optimistic 10 years ago about the practical application of precision medicine. And I would say it’s been just as bad as my expectation,” Califf responded.
He noted that there has been tremendous progress in the understanding of human biology and in the theory of how precision medicine should work. But that’s as far as the benefits go, noting how his younger brother recently died of pancreatic cancer despite the most knowledgeable experts working on his case.
“The practice of precision medicine and the place where it should be the most advanced is pathetic. And I think in clinical practice we’re still in an era where just getting the right dose of drugs for serum creatinine is a major problem. The idea that a person with pancreatic cancer has got to shop around to our best cancer centers to find a protocol, it is just not right. But the same would hold for a person that comes in with a creatinine of two and needs to be on a renally adjusted dose of a drug. And the idea that a doctor using the cerebral cortex of one individual human being can’t even remember that is not a very smart thing. Let’s let machines do the things that machines do better and let the human part focus on the oversight and the interaction with people that’s needed. So yeah, I think it’s just as bad as I thought it was going to be back then.”
His Advice for his Successor at the FDA: Marty Makary
Califf expressed his hope that Marty Makary, nominated by President Trump to lead the agency, would trust in the expertise and the independence of the FDA.
He explained that a big part of the job is fielding calls from lobbyists, from people trying to influence Congress and even deal with threats of budgetary cuts from any Congressional leader who feels slighted for some reason.
“So the main advice is trust in the expertise of the people that work at the FDA and get to know them well and when making changes, make sure that they’re involved in it, and then focus on evidence, – still a lot of work to do to get the evidence right,” he said.
