Reviewing 2023 with FDA Commissioner Robert M. Califf, MD

Since 2017, HCPLive has published hundreds of end-of-year feature articles and multimedia reviews as part of the annual This Year in Medicine series. Over those 7 years, the most returned-to subjects by our staff and clinician experts alike have pertained to key decisions from the US Food and Drug Administration (FDA): more often than not, when a specialist is asked, ‘What was the biggest news in your field this year?’ their mind goes to practice-changing drug approval or regulatory decisions. Just read our advisory board’s top story picks this year to see for yourself.

At the end of what’s been yet another unprecedented year in medicine, HCPLive had the opportunity to speak with FDA Commissioner Robert M. Califf, MD, on a number of developments that will likely define his and his peers’ 2023. Califf, both the current and a former FDA commissioner—first under the Obama administration from February 2016 - January 2017—is concluding his first full year at the position under the Biden administration since being sworn in last February. And as he discussed, it has been as eventful a tenure as one could imagine.

“The day I was confirmed was the day of the infant formula recall that happened at Abbott, which created daily work by me with the foods team and dealing with that crisis,” Califf said. “And that led to a lot of thinking about what should be done with the foods program. After all, the ‘F’ in FDA does stand for food—people often forget that.”

Indeed, Califf highlighted a myriad of evaluations and contributions toward food regulation, cosmetics, dietary supplements among his chief roles this year—emphasizing the significance of the FDA’s involvement in these matters just the same as, say, major drug approvals for Alzheimer’s disease and weight loss. Throughout his discussion with HCPLive, Califf returned to a pair of his priorities from this last year—combatting the “misinformation crisis” and fostering time-efficient evidence generation.

“It's a huge issue for us—as the world is changed around us, how we communicate and the impact of that communication is critical,” Califf said. “And then a focus of my entire career...is on evidence generation. You know, I was a busy cardiologist working in intensive care units and an outpatient clinic for most of my career. And it always struck me that I felt better about how decisions I made with patients when those decisions were informed by high-quality evidence, but there's so much of what we have to decide upon—either policies or individual patient decisions or consumer decisions, where the evidence just isn't there. And yet, we now have information technology that should make it very inexpensive, and relatively quick to get answers to questions so that we can improve our health with high quality evidence for these decisions.”

In the 7-part video series above, Califf reflects on various disease trends, drug approvals, public health crises, and regulatory actions that helped to define this year in medicine. Here are some notable quotes from the conversation.

On the future utility, and regulation of generative artificial intelligence (AI) in medicine:

“Like I say, I was a busy practitioner, and if I think back to how often in clinic, I had to say, 'Wow, there's something here, but I don't have time to delve into the details. I'll deal with it next time I see this person...' In an AI environment with infinite processing, you can take on all those dimensions. But there's a lot of reason to be scared, because leaving an automation to control itself could lead to a very detrimental processing of information and recommendation. So that'd be critical, that we figure out how to regulate this.

It's going to be really important for the clinical community to get up to speed on this. In order to really understand either predictive or generative AI, we need to be able to know for each individual person, their trajectory of their health over time, because an AI model left in place with no tuning, almost 100% of the time, is going to degenerate and start making worse predictions unless it's constantly kept in tune.”

On the approval of numerous gene and cell therapies to address previously untreated diseases this year:

“We're going to see this is just the beginning—we're going to see a huge number of cell and gene therapies. But we also have a lot to learn. If you ask about, 'What are the off-target effects of inserting a gene or deleting a gene?' You know, we feel good enough now that these things should go on the market, but we're going to have a lot to learn in the postmarket phase, and we'll get better and better at it. There's also the cost issue, which is not the lane of the FDA. We're prohibited by law from considering costs. But if we want these treatments to be available for rural people and people who have trouble having jobs because of their diseases, we're going to have to figure out how to make it affordable and accessible. So we're doing a lot of work with CMS...we don't tell CMS what to do, they don't tell us what to do at FDA. But I think of it as a baton hand-off; we run a lab in the pre-market phase to make sure the treatment is safe and effective for a group of people for a given condition, and CMS has got to figure out how do we implement this, who else you know who should be treated, who should be excluded?”

On the industry’s transition to annual COVID-19 vaccine booster doses:

“There are billions of people now who have received the current vaccines we'll continue to follow. Every vaccine has side effects and toxicities; we need to make sure those are followed up on and that we understand them as much as we can. But so far, every updated vaccine has reduced the risk of death and hospitalization in the relevant population by a very significant amount. And it brings out the misinformation issue, which has been hard to deal with.

There are efforts, I think, to confuse the public about the benefit-risk balance with vaccination that is beginning to spill over into vaccination in general. Whole diseases that have essentially been eradicated like measles are reappearing now, due to the reduction in vaccination that we're seeing.”

On the impact of substance use crises and poor mental health on the US life expectancy:

“These things are interrelated, but not identical. The whole mental health situation in the United States is very concerning. And, frankly, we're not seeing tremendous growth in new medical products on the drug side, for mental health. The behavioral side, as it relates to digital technologies, is in our remit—but not the pure behavioral side. And so, we're working hard this year to see what we can do to work across FDA to integrate these various elements into at least a better comprehensive approach to mental health, which is a very deep and important part of this decline in life expectancy that we're seeing.”

On drug development that addresses declining overall maternal, gestational and newborn health

“We've got a real problem with maternal and fetal mortality in the United States, and we're not seeing a flood of new products coming through. And it's an area of policy that we're going to need to work on, because having worked on drug development for a large part of my career, I think a very big part of the problem is liability. Doing the clinical trials that are needed in pregnant women carry significant liability. We're going to have to do something to create a system where these trials are more attractive, because if you're an investor in the pharmaceutical industry, that's just not a place where investors feel good because of the risk involved in product development. The good news is we're going have better and better targets. We understand the biology more and more; we've just got to make it so there's a pipeline of products here.”

On the robust research and development of targeted agents for clinical weight loss in cardiovascular and cardiometabolic patients:

“What's in addition to the just the phenomenology of the clinical trial results and applying those to this enormous part of the US population which could benefit, this exploitation of these pathways, pharmacologically—there are at least 19 different variations on the theme that are in development now—preliminary data is indicating that maybe the circuits in the brain that are affected have to do with addiction in general. So, maybe this is going to be a treatment for drug addiction, for tobacco addiction. And it also begins to point to the possibility that things like ultra-processed foods may be triggering addiction circuits in the brain that need to be broken by the pharmacology.”