Posted 08 May 2013
By Alexander Gaffney, RF News Editor
What comes to mind when you think about federal agencies that affect healthcare product regulation? If you're like many, the first agency to come to mind is the US Food and Drug Administration (FDA), followed by others like the Drug Enforcement Administration (DEA) and the Federal Trade Commission (FTC).
But a lesser-known agency called the National Center for Advancing Translational Sciences (NCATS) may soon be as integral to the regulatory process as FDA is, thanks to a large amount of funding and a new mission to help solve regulatory problems where no incentive yet exists. Formed in 2011 by Francis Collins, director of the National Institutes of Health (NIH), NCATS only recently got its first permanent director, Chris Austin, who is charged with running the 250-person agency and overseeing its $575 million in funding as it attempts to take on some of the most intractable problems in drug development.
With this in mind, we recently sat down with Chris to talk about his role at the organization, the promise of NCATS, regulatory science, translating discoveries, teaching the public about the drug development process and what the future of regulatory looks like.
Miss an earlier or later part of this interview? Check them out here: (Part Two) (Part Three)
Regulatory Focus: Thanks for speaking with me today, Chris. You're relatively new to NCATS, as is everyone there given the age of the organization. Can you tell me a little bit about yourself?
Chris Austin: Sure. I'm a clinical neurologist by training on the medical side, and I'm a geneticist on the research side. So I have the goalposts on either end, and the translational aspect is in the middle. My interest in this from the very beginning has been to bring these two worlds together. That is, to bring the very elegant and wonderful scientific discoveries that are now possible and have been made to the benefit of all kinds of patients, and in particular the kinds of patients I couldn't treat when I was a neurologist. That's really what drives me.
I spent a while at Merck, and while there learned all of what we now call translation, though I'm not sure it was called that then, and got quite involved in a number of regulatory issues associated with the early days of pharmacogenetics. Then, for a variety of reasons, left Merck to join NIH in 2003, initially to be the translation guy at the genome institute right about the time the genome project was getting finished. So a lot of the programs that I started over the last decade were really genome-function projects, but they bled into novel product development for reasons you can imagine.
Everything that I've been doing for the past decade has been in the target-validation space, working in the first-in-human trials stage to develop novel technologies, paradigms and tools to transcend previously untreatable diseases and unprecedented targets.
I took this job about seven months ago. To me, it really is a synthesis of all of the things that I have done in my career. NCATS has all of the programs that I used to run in it now, including the office of rare diseases-there are a lot of rare diseases that I grew up with clinically-the clinical translational science award program, etc.
RF: What do you see as the purpose and promise of NCATS?
CA: NCATS was started because of a push and a pull.
"Push" is the avalanche of basic understanding of health and disease, perhaps exemplified by the genome project. Many other examples of basic science and the understanding of disease have happened over the last five decades, but have really accelerated in the last 10-15 years. There is a real feeling of urgency that employees at NIH feel to deliver on that promise to tangibly improve health. That's the push.
The "pull" is the state of the current process of translation, which whether one talks about drug-device diagnostic development, or talks about implementation of interventions once they get approved by FDA, if indeed they have to be approved at all.
Our industry track record to apply those interventions in all patients who could stand to benefit from them is just as poor as our record and our efficiency at developing those interventions in the first place.
Those are fundamentally scientific problems on the one hand, and they're operational problems on the other.
"Our industry track record to apply those interventions … is just as poor as our record at developing those interventions in the first place."
There are many scientific problems which apply across the translational spectrum, which have been-up until NCATS-no one's specific day job. They are general problems which prevent efficiency in translational sciences and product development. It's regulatory-directed work if we want to think of it like there, but there are a whole bunch of problems that are distal to that. NCATS was formed not to develop treatments or interventions for a particular disease, but rather to focus on the general scientific and operational problems which prevent this translation from basic understanding into interventions which improve human health.
RF: Could you give some examples of what you're talking about here?
CA: There are really three main problems: The preclinical predictive toxicology problem, the predictive efficacy problem, and the business side of the preclinical world.
If you look at the three main reasons that drugs fail, it's lack of efficacy, toxicity, and business reasons. And business reasons has to do with an adverse risk profile, either because the target is risky or the population is risky, or the population is small. NCATS works in that space on all those problems specifically, not just from the scientific point of view, but also from the operational point of view.
One thing that's very clear in this space, both in the preclinical space and the clinical space, is that about half the time the problems are scientific, and the other half the problems are collaboration problems, incentive problems, IP problems, credit problems… because we had a research system, at least in the public sector, which is designed to do one thing: fundamental research, which it does extremely well. But that structure does not work for a variety of reasons in the translational space.
"Three main reasons that drugs fail: Lack of efficacy, toxicity, and business reasons."
NCATS works a lot on collaborative paradigms, strategic alliance paradigms, which we think are going to be just as important as solving the fundamental underlying scientific problems of making translation more predictive.
So we have, in our place, the mantra of the three "Ds": Develop, demonstrate and disseminate.
Development includes novel tools and technologies, paradigms in everything from novel chemical libraries to address novel parts of chemical space, novel ways to do target validation better, the intervention development process, regulatory science, adaptive clinical trial designs, novel ways to do clinical trial recruitment, diagnostic criteria, endpoint criteria that are going to meet regulatory muster, and more.
If you notice, none of those things have a disease in the name. Another way that I sometimes characterize this is that NCATS is an adapter from traditional research and traditional commercialization like regulatory-directed product development.
Another term I use to characterize this is that NCATS works in the tragedy of the commons space. We work in the space where a problem affects everyone, but nobody's problem in particular, so nobody tends to work on them
RF: How do you get industry and FDA to come in and partner with you given the misaligned incentive structure?
CA: You've put your finger on one of the reasons why NCATS exists. NCATS is really kind of a third way, if you will. It has been exceedingly easy for us to strike up collaborations with both industry and FDA, albeit for somewhat different reasons.
"FDA is exceedingly interested in novel ways of evaluating the safety and efficacy of the products that they see."
We collaborate with industry on sort of two levels. The first is a sort of general pre-competitive data/research tools, like the collaboration we're doing now with Eli Lilly. Or they are direct collaborations, usually with small companies to de-risk individual, unprecedented targets, or untreated diseases, or rare diseases, so that somebody can make a business case for somebody to adopt them. We do a lot of that.
On the FDA side, what's been interesting is that FDA is exceedingly interested in novel ways of evaluating the safety and efficacy of the products that they see. And they have a lot of information about when things go wrong. Unfortunately, they have less information about when things go right.
The problem is that they have no ability, either statutorily or financially, to address those common problems because they're not a research agency. So when we came in, we said, "Look-we don't have a particular disease ax to grind. We're interested in solving the big problems which you see over and over and over again coming to you in product development applications."
And they have been extremely enthusiastic to work with us on those issues. Our attitude is that we're going to work on the problems that FDA has helped us to identify, because those are the problems we want to work on. We're very dedicated to useful deliverables, and if you're going to develop those, you have to do what might be called market research.
So our conversations with FDA and the pharmaceutical industry are market research, because those are the entities that are going to be using the science that we develop. We don't want to just be a center that puts science out there and publishes nice papers that nobody ever uses. That will be a failure, as far as I'm concerned, if NCATS ever does that.
"We don't want to just be a center that puts science out there and publishes
nice papers that nobody ever uses. That will be a failure, as far as I'm
concerned, if NCATS ever does that."
Getting back to my "Three Ds"-Develop, demonstrate and disseminate-we have to not only develop these novel tools, technologies and paradigms, but we have to demonstrate in individual use cases (target, disease, intervention, etc) that this novel approach actually does make a difference. Then, if it does get demonstrated as being such, to disseminate the tools in a very purposeful way to the rest of the community. We can't assume that the community is just going to accept it on their own, because we know that doesn't happen. The data are very clear.
RF: From a funding perspective, NCATS has decent, though limited, funding. You're talking about a complete overhaul of the regulatory paradigm. How do you leverage your funds to maximize your returns? What other entities are you partnering with?
CA: NCATS has a $575 million budget or so. It's important to remember that NCATS was not founded with new money. Its creation was revenue neutral because it was a reorganization of existing NIH entities. There is no new money, so we are gaining efficiencies through adjacencies and adapting old programs to meet the new NCATS mission.
But yes, you're right. These problems are so large and have been so intractable. Just look at Eroom's law. That graph scares the heck out of me, because it has been absolutely inexorable since 1950 despite every change in science and medicine. NCATS is a catalyst. We're just 2% of the NIH budget, but we plan to be very productive, which is to bring together reagents or reactants which are inert by themselves, but when we bring them together, they produce things that they otherwise wouldn't or couldn't.
do not have a sufficient level of hubris to think that we're going to solve
this problem by ourselves."
We believe very strongly around here that translation is a team sport, so that every one of our projects is collaborative. Those collaborations are not only among individuals with different expertise-biology, chemistry, engineering, pharmacology, regulatory, etc-though we do those things as well. If you expand that to the ecosystem problem, NCATS as an adapter lives in a slightly difference ecosystem from the rest of the NIH institutes. Our ecosystem includes FDA, biotech, pharma, VCs, patient groups, academics and other researchers who are traditionally NIH's constituents.
So you'll see in one of our projects, the tissue chip program, that's a classic NCATS program in that it is a very difficult problem which lots of people have broken their swords over. It is also a very important problem, in that if we can solve it, it would result in logarithmic change and improvement in the translational science process. But we do not have a sufficient level of hubris to think that we're going to solve this problem by ourselves. Now, we have certain ideas, but we know that we have to bring in a variety of different points of view, and that includes DARPA, which has a different way of doing things operationally. It's not just the science, but the operations that matter: How do you get stuff done?
And of course FDA, which is going to be the one to use these devices if they're ever approved, is involved as well. And the people who are doing this work are folks who are bioengineering people, and others in the academic world and the industry world, whose ideas we're now canvassing. We're doing this in a very project-managed way with very clear deliverables and go/no-go decisions and staged progress to make sure that we actually have a deliverable at the end of the day.
Enjoying this interview? Check out parts two and three: (Part Two) (Part Three)