Straight talk from the FDA
Janet Woodcock takes questions from the audience. Photo: Christine Fu
Clinical research and drug discovery in the United States are in need of a serious overhaul, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, told an audience of nearly 300 in Byers Auditorium at UCSF Mission Bay on Thursday.
Perhaps the most interesting segment of her talk was the Q&A session at the end, which highlighted her deep knowledge of drug discovery and regulation. A lightly-edited version follows.
Audience member: You think about this as an incredibly capital intensive, risky, research-heavy enterprise, one that the private sector seems to be getting out of—is there a role for government?
Woodcock: The FDA—we’re supposed to be a regulatory agency…I believe the NIH is trying to address this problem with NCATS (the National Center for Advancing Translational Sciences). So they’re trying to do something but they haven’t received a lot of funding. I’m not sure they have a clear concept of what needs to be done… I think the NCATS concept will be advanced and that will be the federal government’s effort in this area.
Audience member: Do you personally think the “complete response” letter should be made public?
Woodcock: In the user fee program the industry submits a marketing application to the FDA…we have a certain amount of time to get it all reviewed and then we’ll send them back a complete response—or we’ll approve the drug. So a “complete response” means we didn’t approve the drug. A lot of people would like to hear about that transaction. Because the investors would like to hear where they’re being spun by the company; the public would like to hear; many of my staff would like to make it public because they want our side of the story to get out there; like, why did we turn this down? There are points on either side of this, and this would probably be for Congress to decide because it has to do with IP and confidential commercial information versus transparency of the process and investors’ rights. So I don’t know enough about economics to have an opinion. I usually favor transparency in all things because I think it eventually solves a lot of problems.
Audience member: Shouldn’t NCATS work closely with the FDA? Why does it seem from an outsider’s perspective that NCATS is stuck?
Woodcock: Well, they don’t have a director, they’re in the process of selecting a director and I think they’re waiting to get that leadership in place. Right now they’re merely an amalgam of other programs that were committed funds…so they don’t have a lot of freedom to operate. So it’s going to take a while for them to reveal the promise of what NCATS is going to be.
Jeff Bluestone, executive vice-chancellor and provost, UCSF: What’s the FDA doing in thinking about how we’re going to deal with some of the unique challenges that cell-based challenges provide?
Woodcock: I was involved in that a long time ago, but I’m not anymore, and the Center for Biologics regulates cell-based therapies. What I understand from them is what they’re concerned about is rigor, that there be some kind of characterization of what is the phenotype of the cell so you have some kind of reproducible manufacturing. That’s the level where they’re really focusing right now. But I don’t know all the other challenges. I think that therapies from regenerative medicine will really become prominent in the future, will create lots of struggles.
Laura Esserman, professor of surgery and radiology, and director of the Carol Franc Buck Breast Care Center, UCSF: Do you have a recommendation for how to engage the venture community in helping us build the new infrastructure that would allow us to make some of these transformational changes?
Woodcock: The venture community told me that they represent mainly pension funds. Old people’s money. And their job is to have a substantial return on investment within a four-year horizon. So they have a short time horizon and they need some predictable return after an investment is made, otherwise they’ll lose money for the pension fund. So they are not the entrepreneurial types that they may sell themselves as. They’re conservative. I’d be conservative too. That’s why they’re fleeing toward less risky investments.
Audience member: There are many competing agendas. How do you make it win-win for all the players? Could the FDA help?
Woodcock: I’ve found that our presence at the table is kind of validating. The FDA is really scary, so if we’re there it must really be important. And so we try to add our weight to the dialog. But we aren’t economists. That’s not our area of expertise. So how to make sure the system is altered in ways to provide a return on investment to everyone is not our expertise. But the problem is our problem too. We own the problem because if this enterprise fails…if we had no FDA standards, then lots of drugs could get on the market. But there might be reimbursement problems! So there is some relationship there that we have to own.
Audience member: Funding is flat. The cost is going up. So if academia has to take part in it, how is funding going to come to academia?
Woodcock: Academia is in charge of the study sections. You’re not completely helpless on what the research agenda might be, although you might feel totally helpless. In some ways there has to be more scholarly endeavor across the whole range of human biology, not just the very reductionistic level. That’s not a good answer, I know, but everyone has to own this problem.
Audience member: The flat portion of funding happens at the clinical research stage where the costs are very high. So how is the funding going to come?
Woodcock: I think we have to figure a way to make the cost lower and that’s what I’m working with Laura Esserman and other people on. It doesn’t have to cost that much. If you sat down and devised this, and you’re a systems engineer, they’d commit you. You put the sites where the patients aren’t, and you make huge barriers to initiating the enterprise, etcetera, and you do it over and over again, which is the definition of being crazy. So it isn’t like I expect academia to bear these costs. I think we have to work together to lower the cost. And improve the effectiveness and efficiency of clinical evaluation. Especially since now, if you’re going to do this right, you have to be iterative between the bench and the clinic.
Audience member: Is there a way that valuable data can be collected in randomized studies, post-marketing, while companies are collecting revenue to help pay for those studies? Before you get your first dollar in the door, it’s a billion dollars and ten or fifteen years out.
Woodcock: I’ve put before Congress with the Infectious Disease Society of America the concept of a limited population antibiotic drug —maybe a tiny development program, a couple hundred patients to test a drug to treat a drug-resistant organism. You get on the market and you have a logo and then you have instructions on the label saying ‘this is only to be used for this purpose’. And that would provide good antibiotic stewardship, and also if companies wanted it, they could continue developing the drug. Current drug trials are 5000 people, a major undertaking, which is why most companies have gotten out of the business
Audience member: So what’s the resistance to doing more of that in diabetes, cardiovascular?
Woodcock: We don’t have a tool. If I don’t get it in the statute, we’ll have to go to rulemaking, which would take forever. There are probably groups that would throw themselves bodily in front of it to prevent it from going into effect. Because people don’t like change, they feel threatened… Some of the companies are resisting. There’s a lack of trust among all the sectors. What you’re bringing up is staged approval mechanism. You can’t have staged unless, once it gets on the market, there’s some mechanism where people are willing to not use it. The previous paradigm was, you try to get it in as many people as possible, and that’s how things came to grief many times. Getting to some kind of staged mechanisms would be a good move.