COMMENTARY

Dr Rob Califf on His Short-Lived Tenure as FDA Commissioner

Interviewer: Robert A. Harrington, MD; Interviewee: Robert M. Califf, MD

Disclosures

July 06, 2017

Robert A. Harrington, MD: Hi. This is Bob Harrington from Stanford University on Medscape Cardiology and theheart.org. Over the years of doing these podcasts, I've really enjoyed the opportunity to talk with colleagues and friends in the field who are doing interesting things, broadly defined.

Robert M. Califf, MD

Today is a great example of that. My guest is Rob Califf, a friend and colleague for many years who recently served as the commissioner of the US Food and Drug Administration (FDA) and who now is following the role by doing some interesting things at Duke University, at Verily in the tech community, at PCORnet, at Stanford University, and I'll say maybe more broadly in the world of healthcare technology.

Rob Califf is the former professor of cardiology in the Department of Medicine at Duke University. He's also recently been named the vice chancellor of health data science at Duke University. He is an advisor to Verily, formerly known as Google Life Sciences, and we're also pleased that he's going to be spending some time with us on campus as an adjunct professor here at Stanford University. Rob, thanks for joining us here on Medscape Cardiology.

Robert M. Califf, MD: Good to be here.

Dr Harrington: Rob, many in the community know you through many years of your work in cardiovascular research, particularly in large-scale clinical trials; and while you interacted with the FDA many, many times over the years, during the last few years you got a different vantage point—first as the deputy commissioner at FDA and then for the last year of the Obama administration as the commissioner of the FDA. Let's start with the broadest question: Why did you decide to do that when asked?

Dr Califf: There are times in your life when you feel like you've accomplished certain things, and you're ready for the next adventure. Up until a couple of years ago, that next adventure had always been on campus here at Duke, where I moved from one job to another. The time just seemed right to do something entirely different, and the opportunity to go to the FDA was something I really always wanted to do. I think people know that, by nature, I'm an evaluator, and that's the ultimate evaluation machine.

The Confirmation Process

Dr Harrington: You had an interesting confirmation process where your prior relationships with industry, which had been almost exclusively around clinical research, were heavily scrutinized. Talk a little bit about that experience.

Dr Califf: First of all, I feel like I got the best of all worlds. I went in as a civil servant, a career employee at the FDA, where I was protected from the peer political interchange, and I got to do a lot of work with the medical products and tobacco areas reporting to me. That's a little over half of the total FDA; most of the rest of it deals with food. I came on the premise that it was likely that I'd be asked to be commissioner, but it had been made clear to me that the President has to ask you to be the commissioner. It's not something you apply for.

Eventually I was invited to the Oval Office to meet one on one with the President. It was quite a fascinating meeting. The first 10 minutes were spent with the President telling me how much he hates Duke basketball and loves the Tar Heels. Once we got that behind us, we had a fascinating discussion about technology development and its relevance to the wellbeing and the economy of the United States. You walk out of the Oval Office, and you think, holy smokes, I've been one on one with the President, and he's offered me a job. The world is great, and then the next thing that happens is you are intercepted by a team of people who are your handlers, who remind you that the President can offer you the job, but you don't have it until the Senate confirms the nomination.

That process was just amazing because the relationships were not great between the administration and the Republican-led Senate. Fortunately, I had senators Alexander and Burr, who really helped me get through it, and it turned out it was mostly the Democrats who didn't like the fact that I had an industry background.

Senator Sanders never really liked me very much...but, as I like to point out, my mom got him back.

Dr Harrington: It was interesting to follow, wasn't it? Richard Burr, among the most conservative of Republican senators, actually was very much on your side. I remember watching the open confirmation hearings where he, in his role as a North Carolina senator, also had the privilege of introducing you to his Senate colleagues and was quite laudatory in his remarks; and then we had the other side of the aisle, maybe most notably with Senators Warren and Sanders. They weren't initially so favorable, were they?

Dr Califf: Well, here I would distinguish between the two of them, and also it was really nice of Senator Burr to introduce my granddaughter, who at the time was 12, to the Senate formally, which was fantastic for the family. Senator Warren put me through hell but, in the end, became a big supporter. We spent a lot of time talking about how clinical trials worked and why you need industry partnerships to get the right answer. It's interesting—among all the things that politicians need to know, understanding exactly how clinical trials are done is not high on the list.

It's a widespread belief that the National Institutes of Health actually does the trials or that the industry sponsor does the trials. Once we went through it all, she really came to appreciate the model that we had developed here at Duke and that many academics used.

Senator Sanders never really liked me very much, and that showed up at the hearing; but, as I like to point out, my mom got him back. She was 88 at the time, a retired schoolteacher; and after the hearing, while we were waiting along the side, she saw the Senate mailboxes and just wrote him a note and put it in his mailbox. I feel like we came out even on that one. He never really took the time to understand how the research actually is done.

Dr Harrington: Not only that, it was very interesting watching his remarks from that political theatre; he likes to shout about drug prices. I did appreciate that you reminded him in a very collegial manner that the FDA actually did not set pharmaceutical drug prices. That didn't seem to deter him that you would not have the ability to set prices.

Dr Califf: No, it really didn't. You learn that they're all individuals, they all represent constituencies, and they all have pluses and minuses just like we do. It was fascinating and interesting to learn how to navigate that. Of course, it culminates in the most amazing decision whether you get the job, where each senator goes out one by one publicly on C-SPAN and votes yes or no as to whether you should get the job. I had to sit and watch that, which is quite interesting, but it came out well; and overall it was a tremendous experience for me.

Dr Harrington: You prevailed. It was quite a convincing bipartisan level of support. You moved into the job, and from my conversations with you over that year, you really were having a good time. You really enjoyed the job, spending your days doing everything from hearing people defend the Constitution and the Bill of Rights and discussing freedom of speech to things where you really got to see an amazing dedication to science and the public health.

Dr Harrington: Give the audience a couple of the highlights of what you walked away impressed with from how the FDA works that the average cardiovascular community member might not understand or might not appreciate.

Dr Califf: The FDA all together is 22,000 people, 17,000 full-time government employees and 5000 contractors, many of whom are there long-term to help with particular technical issues. They're really dedicated to public health and, I think as everyone knows, not terribly highly paid for the work that they do but interfacing with 20% of the economy, which is what the FDA regulates. As commissioner, it was amazing to see the amount of scientific knowledge and expertise and blood, sweat, and tears that went into preparing presentations for policy decisions to be made.

The politicians are not bad people. They're just under a lot of pressure and often are fed bad information by people.

Also, there's a fierce protection of the role of a nonconflicted federal employee and making the decision about individual products, something that I really came to appreciate. I can assure you: If you let the political system invade those individual product decisions, there'll be no stopping it. As commissioner, you're the person between the workforce and all of the politicians. Again, I'll reiterate that the politicians are not bad people. They're just under a lot of pressure and often are fed bad information by people.

The Duchenne Drug Decision

Dr Harrington: Well, you would be one of the few commissioners who had a deep understanding of the clinical science that goes into producing the data, focusing on drugs and devices, as opposed to the food and tobacco part of your job; or, as you like to talk, about the cosmetics part of your job. On the science side, one of the areas that underwent a great deal of scrutiny was the muscular dystrophy issue, where a product was really felt to be unfavorable for approval by the review agency; but when it got to a higher level of scientific review, it was viewed favorably. Then you wrote a very interesting decision, where you weighted less into the science, but you defended the policy approval or the science approval process.

Do you want to comment on this, Rob? This something that has gotten a great deal of press as people think about the level of evidence required for FDA approval and how common diseases might vary from rare diseases. It brings in the issues of patient advocacy groups; a lot of things that people know about but may not understand how it all comes together.

Dr Califf: Well, first of all I just want to point out that its interesting how often the press and popular discourse get off on the spectator sport part of this because so much of the economy is affected by the decisions the FDA makes. Of course, people love personalities and when there's an argument. A couple quick things about this: The FDA is given special power by law in the drug approval process for when there's a disease that's severe, like life-threatening, for which there is no treatment; the process is called accelerated approval. Under those conditions, the FDA is instructed to look at all of the available data, including unvalidated biomarkers, to make a decision based on the totality of the evidence that can be brought to bear. If the decision is favorable, there's requirement for the sponsor to then do definitive clinical trials so it would meet the usual standard in the postmarket phase.

The key issue is to keep politics out of approval decisions.

That's what happened with this drug for Duchenne muscular dystrophy. For the cardiologists in the audience who don't deal with this every day, that's a rare genetic disease that affects boys who typically die in their teens or late twenties after a progressive downhill course. While steroids have a slight effect most likely, there's really no proven treatment that changes the course of the disease. This compound that was studied and brought to bear was really poorly done, I have to say. I won't go through the details here in the interest of time, but in the opinion that we wrote, we did dive very deeply into the science. This was the ultimate decision for me; this is the first time in history that an internal argument in the FDA had been appealed to the commissioner. Of course, as commissioner, you're a political appointee. I basically said that the highest level of civil servant should make this decision, which was Janet Woodcock; and having worked with Janet for years, I had no qualms about her competence and also her interest in what's good for the patient.

This in no way should be interpreted as a precedent for the typical drug approval; it was just a social circumstance. The key issue is to keep politics out of approval decisions.

Dr Harrington: Well said, and I'm glad we were able to get you on the record talking about that.

My guest today has been Rob Califf from Duke University, Stanford University, and Verily. Rob, thanks for joining us today on theheart.org | Medscape Cardiology.

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