Who would volunteer for one of the government’s toughest jobs just when Congress had given it a 157-page new law to implement? That’s the challenge Janet Woodcock decided she wanted last month as commissioner Andrew von Eschenbach was reviewing “some outstanding people” who’d applied to be CDER’s permanent director, a job Woodcock had left after 11 years in 2005 and had returned to last September on an acting basis until von Eschenbach could find someone to fill it. She was not among those who responded to the nationwide search that began in December.
It was the FDA Amendments Act’s (FDAAA) pharmacovigilence provisions that became the “tipping point” in her change of mind, Woodcock indicated in an interview last week. Already the longest serving drugs director at the time of her promotion to deputy commissioner for operations (two years longer than J. Richard Crout, 1973-82), Woodcock might have had enough of CDER by the time she’d spent another five months in that chair and von Eschenbach was closing in on a choice in February.
“But it had been a lot of months by then,” Woodcock told us. “We were in a real inflexion point for the Center where they had received the Amendments Act, a new user fee program — many, many new requirements under the Amendments Act. So I volunteered. I could see the need for someone to hit the ground running. I know what a steep learning curve it is, to run such a complex organization, and I felt there was very little time for somebody to come up to speed.”
But what particularly attracted her, she said, was “tremendous scientific opportunity” she saw in FDAAA’s pharmacovigilance provisions. The CDER director would lead their implementation. “I’m very excited about that,” she told us. “Our ability to access health records to better evaluate the safety and the performance of the nation’s drug armamentarium on a real-time basis and on a population basis after-market is really a tremendous scientific opportunity.”
In our interview, Woodcock reflected on her accomplishments in the Commissioner’s Office, changes she found on her return to CDER, her interest in optimizing the nation’s therapeutics armamentarium, the Critical Path Initiative, the policy issues raised by reactions to the Vytorin/Zetia LDL cholesterol study, her role in pushing more early communications on drug safety, criticism of Drug Safety Oversight Board transparency, the FOIA processing backlog at CDER, and the Center’s readiness to implement FDAAA provisions.
Q: Before you came to FDA, you taught at UCSF and also at Hershey Medical Center, where two of our former commissioners also arose from. Maybe you got to know both of them then?
Well, I knew Art Hayes very well. It was very funny when he came and told me he was going to be FDA commissioner, I literally said to him: Why would you want to do that? He was a clinical pharmacologist and he gave me a very reasoned explanation about that. At the time, FDA was the last thing on my mind.
Q: More than a few people since your permanent appointment announcement have asked that same question about you. Why would you want to do that?
I’ve had some time at the Commissioner’s Office, doing something very different than being a line manager of a large organization. I think I’ve accomplished a lot with Critical Path and Bioinformatics Board and Management Council, and the number of things I’ve set in place when I was there. Now I’m ready again for different types of challenges. I am really somebody who likes to be an executive and I think I bring a lot to that kind of position.
Q: In your four years of absence from CDER, have you noticed any significant changes to the CDER that you had left?
Certainly some people have left. There have been the usual changes in personnel. There have been some changes in how things operate, but I sense the Center management is very strong.
Q: So what was it like? Settling back into a warm comfortable chair you were well used to?
No, it was like stepping into a warm, comfortable maelstrom!
Q: What about any pet projects you’d like to advance now?
I take a very pragmatic view toward management. We need to get done all the directions that Congress has given us under the Amendments Act, as well as other statutory mandates. When I first took over CDER, I really hoped as a physician to deal with the armamentarium — what kind of therapeutic armamentarium do we have in this country? What needs to be done to refine that? But there were so many management jobs to do at CDER that I spent much of the first time at CDER in organizing the Center, implementing user fee programs, and making it run smoothly. So now I think it is running, the management structure is in place, and procedures, and they persist, usually, so I won’t have to do as much of that. So I can get more to issues, such as drug safety, that I would like to have addressed more the first time.
Q: What is your goal with respect to the therapeutic armamentarium?
Basically, it relates to many things people are talking about — drug safety, making sure that unapproved drugs are off the market or get them approved, making sure that the medications that are available are effective and safe, and that they remain that way, not just focusing on the premarket review. Some of the drugs that we have taken off the market were good for their time, but as safer or more effective drugs became available, those drugs were no longer adequate. It’s an ongoing approach. As science advances, you need to look at the armamentarium and make sure that it’s appropriate.
Q: Any other things you want to get done?
I’m going to continue with Critical Path and the pharmacovigilance provisions that are in the Amendments Act are a big project for me, and I’m going to be continuing to lead that. I’m very excited about that. Our ability to access health records to better evaluate the safety and the performance of the armentarium on a real-time basis and on a population basis after markets is really a tremendous scientific opportunity.
Q: With regard to the public uncertainty that seems to have arisen about LDL cholesterol lowering in the wake of the Vytorin/Zetia situation, how does FDA respond, if it chooses to, to such perceptional issues that may not be correct? Or should FDA confine itself to the hard science?
We have to be careful how we weigh in. We have to maintain our independence, and not appear to be defensive in any one direction or another. With Vytorin, you have people criticizing our use of an extremely well-validated and multiply-vindicated surrogate because of results with an experimental surrogate with unknown validity. We have no idea about the carotid intimal thickness surrogate, as far as its performance goes, and it looked kind of strange in that trial because on the statin it also progressed. Something was not as expected in the entire trial. I don’t know to what extent we should wade into these scientific melees. I believe people are piling-on right now on one side of the argument. Independent reporters and media, if they really want to have some reasoned approach, ought to step back from that. But what we see right now is everybody just piling on to the same message.
Q: But the editorial that accompanied the main NEJM article on Vytorin raised questions about the value of LDL lowering.
But if you look at those things closely, they’re talking about something else. It’s like global warming — you can always find some scientist who’d say, ‘Well, it isn’t exactly like that.’ But they didn’t mean that the climate wasn’t getting warmer — they just had some little nit-pick with the current model. And most of these, if you look at them, whether it is on hemoglobin A1C or on LDL cholesterol, or whatever it is, it’s the scientist saying ‘Well, in this subgroup it may not be as valid,’ or whatever. But anyone who questions the lowering of LDL cholesterol overall is probably, like Bob Temple said, trying to kill the population!
Q: Is this an opportunity for FDA say something publicly, or should you just wait for it to die down naturally?
I don’t know the answer to that. Because there’s such a piling-on right now, it might be seen as FDA being defensive. In this case, I think the data really ought to speak for itself. You’re not going to see cardiologists abandoning treatment with statins, for example, because they know the data. There have been about 50 studies showing not just decreased mortality but decreased claudication, decreased heart attacks, other things, over and over without any real question. What happens with these is there is some little point that the scientists are arguing about, and then the media get on it, and they start throwing the baby out with the bathwater.
Q: That’s what’s been happening. Every news broadcast on TV is interviewing patients who are disturbed about the medicines they have been prescribed.
People don’t like to take medicine. A lot of people may well stop taking their statins because of this. What that will do is cause increased mortality. This gives people an excuse to stop taking their preventive medicines.
Q: Nevertheless, FDA shouldn’t say so?
Well, we would, if we thought it would make a difference, given the current environment. If people think we’re just being defensive, we wouldn’t make a difference, in this environment. We have to think about it. If we could be effective, we would say something.
Q: This is somewhat related to the increased number of early safety notifications that FDA has been issuing for some time now. There has some comment that what you may be doing is dulling public attentiveness, with so many of these. Almost every week there seems to be another one. Are you concerned about that?
Here’s our dilemma. We can not announce these, and then have intermittent ones, leaked and then released by other parties in the most sensationalist way possible, thus worrying the public more, or we can be very open and transparent about the flood of information that comes in and be very clear about how some of this is going to pan out and some isn’t. If you call that ‘dulling’ that could be dulling. But what we’re going to do is follow up on all these, and if it comes to pass that they’re true, we’ll come out with more announcements.
Q: It’s been going on for a while. When did these early notifications begin to be issued?
Since I took over CDER, I made sure the process was effective, so these notifications are getting out in a timely manner. My theory is that to have these announced in the media as some kind of leak or scandal serves the public much less well than having a reasoned, transparent announcement from FDA — ‘This is what we have, we don’t know what to make of it, we’ll let you know if we have more information.’ It’s unsatisfactory, but the time has passed when we could sit on this kind of information.
Q: Have you heard of any negative consequences to this new openness, that people are turning a deaf ear to so much inconclusive information?
I’ve heard some criticism. In most of these we don’t know what people should do — we’re not giving any recommendations. So a deaf ear is OK. The information is out there, you know about it. We don’t tell you what to do.
Q: During your absence from CDER, the Drug Safety Oversight Board was established. It has since come under continuing criticism for holding its meetings in secret and for issuing uninformative, overly-brief public summaries of its proceedings. How can these objections be overcome in the interest of better transparency?
Our public advisory committee on drug safety is Drug Safety & Risk Management. We are not able to hold meetings intended to develop recommendations that include outside (nongovernmental) parties unless they are AC meetings according to the FACA. The DSOB looks at confidential material that we are not able under law to make public; the meetings are not “secret”; they are internal to the government. We take public actions and communicate to the public in a transparent way, but not every government meeting is open to the public.
Q: That relates to another issue on openness. How is CDER handling its FOI backlog, and making the Center more transparent?
It’s very difficult. There are laws about what has to be held back — trade secret, confidential and commercial information. We have to redact those things before anything is put out. We have great difficulty with putting enough resources against that, to get it done. We don’t like the backlog, either. We don’t want to have information that people can’t get, that they’re legally entitled to. However, there are other people who are legally entitled to have it redacted in a perfect manner!
Q: So it’s strictly a resources issue?
Yes. But I’ve talked about having contractors, but we really have to extensively train people to do this because of the legal consequences if we do release something that shouldn’t be in there. We agree, it’s a real problem.
Q: So you can’t offer light at the end of tunnel?
We were directed under the Amendments Act to get things moving. Or maybe it was a petition. We are trying.
Q: Data from FDA haven’t shown any increase in submissions, so where are all these workload pressures coming from that are causing CDER to miss certain PDUFA deadlines?
Well, have you read the Amendments Act? It has literally hundreds, thousands of things we have to do, different timeframes. Most of those relate to drugs. So the drug Center is working extremely hard on implementing those provisions of the Amendments Act. I’ve also directed that safety matters must have first priority.
Q: FDA just released its five-year Drug Safety Plan. Which areas will prove most difficult to implement, and why?
That’s a good question. I read the plan, and I think we’re well underway on the commitments, and our planning for the commitments that are laid out in that plan. So I don’t know that the PDUFA commitments are going to be all difficult.
