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 parts one and two of this interview? Find them here: (Part One) (Part Two)
Regulatory Focus: One of the other things that comes to mind is scale. With many of the projects so far, you're pairing big ambitions with "big pharma." But a lot of the basic research and translation, and especially in the rare disease space, happens through smaller pharmaceutical and biotechnology companies. Many of NCATS' Federal Register notices place a litmus test that participating companies must be able to clear regulatory hurdles-a test that many established companies have the knowledge and resources to meet, but perhaps a smaller company does not. How do you help these smaller companies to participate in the process in light of these regulatory hurdles, and are you working with FDA in regards to this problem?
Chris Austin: We're approaching this issue in two ways. The first is that we're working directly with these smaller companies to get them across the goal line, and much of the process happens through TREND-therapeutics for rare and neglected diseases-and half of the collaborations in the program involve small companies.
In that case, we partner with the companies in a milestone, go/no-go decision way to develop the data packages that are necessary starting anywhere in the lead-up up until just before the filing of an open investigational new drug. But any program in between those two points, we work to get them into first-in-human clinical trials to demonstrate initial safety and efficacy, at which point those companies can leave the nest, as it were, and get the attention of the capital markets.
"Many of these companies do not have either the scientific expertise or the regulatory expertise that big pharmaceutical companies do."
So we incubate them by doing a lot of active work to develop the data package using our dollars and their dollars to solve very directly these regulatory problems. And as your question would suggest, many of these companies do not have either the scientific expertise, the experience, or the regulatory expertise that big pharmaceutical companies do. So we help to supply that expertise, because most of the folks who work at TREND come from pharmaceutical and biotechnology companies, so they've done this before.
This is also an issue, I should tell you, with the academic investigators with whom we collaborate, and perhaps even more so.
In a more indirect way, one of the things that is very clear is that there is, despite FDA making all of their guidances and information available on their website, a real need for a chaperone function which is individualized to the particular problem that the investigator is trying to solve, whether they are in an academic setting or a biotechnology setting. One of the things that NCATS is already doing and very much hope to do more of along with FDA, is to serve as a knowledge base or a convener, if you will, for individuals and companies who are interested in developing their product and have nowhere to get the information.
FDA, I should say, would love to do this on its own, but simply doesn't have the manpower or the mandate to do it.
RF: How many employees work at NCATS right now?
CA: About 250. But realize that about 150 of those employees are in the pre-clinical stage. These folks are actually doing work on collaborative projects. We don't have any independent investigators. Every project is a collaboration with someone somewhere in the world. There are currently about 300 collaborations across every possible area going on right now.
The other 100 are program staff who are involved in extramural grants that are the bulk of what NIH does. About 90% of all NIH funding goes out to outside companies via grants and contracts.
RF: How is NCATS going to define success over the next decade?
CA: It's another great question that we get asked all the time. You know, there is certainly not going to be one success metric. I think about this as a portfolio in that some metrics will be short term, and some will be long term, and they'll be addressed at the issues which have been very well-defined as being the limiting problems in the translational process. I want to be able, in the course of not just ten years or five years, to have tangible deliverables to say that we have developed novel paradigms to address and improve those problems that we've been talking about.
"I want to be able, in the course of not just ten years or five years, to have tangible deliverables to say that we have developed novel paradigms to address and improve those problems that we've been talking about."
That is, we can now predict toxicity better, and here are examples where we have done so. Here are platforms that allow us to assess efficacy better, because that's the other big stumbling block. Here are individual diseases or targets or compounds which have utilized these paradigms, these scientific methods, which demonstrate that our tools have better utility than before.
There will be, I hope, individual treatments-for rare diseases, neglected diseases-which will have been with us, carried through the valley of death, and released into the commercial world and hopefully make it to patients. And I hope that those individual de-risking programs, in addition to being very useful for the individual patients who are affected and the companies developing the products, will be able to tell us something about how to do this process better in general.
I want to be able, within the clinical space, to have demonstrated that we are able to now find diseases better in terms of general ontologies, better define relevant clinical endpoints, paths to develop biomarkers in a more efficient and predictable way, ways to be able to do recruitment for clinical trials in a more efficient way, and have a more integrated and federated IRB structure in this country.
And then all of these other issues distal to product approval, which have to do with translation into general patient populations and then into communities, they're not regulatory issues, but they're ones that I hope to be able to have clear deliverables that show that we've been able to affect those.
Now, keep in mind that in each of these cases, these are really big problems-systemic problems. While I hope that within 10 years we will have affected the entire ecosystem, much shorter than that what we're focusing on is being able to pick out individual use cases in each of these domains that we just mentioned to say, "Here's a better way of doing this. Here's a pilot program." And we hope that in so doing, others will see that there is a better way of doing this, and pick it up on their own.
"I hope that within 10 years we will have affected the entire ecosystem."
Again, we're going to act as a catalyst. We're not going to do everything. We need to demonstrate to others that there's a better way, and then have them pick it up. That is a harder thing to measure, but it is something that we're working on.
I guess the last thing to say about this is that we are thinking a lot about measuring the current state of play now. Everyone knows that none of these processes work very well, but if you're going to demonstrate that you've made them better, you need to be able to show where the processes stand now. And for many of these projects, there just aren't good measurements of how the current systems work. So we're very anxious to establish a baseline, because otherwise five years from now, we're not going to have anything to compare it with.
RF: Is there something at NCATS that you find fascinating but gets, in your opinion, far too little attention?
CA: Yes, there is, and you actually might find this interesting, and it was a surprise to me, and I'm still thinking about how NCATS is going to solve this. I'm going to put this into a purposefully overstated way, so bear with me.
For much of the population-whether it is the scientific population, the public in general, elected representatives, or patients-the translational process is at the very least not understood, and to many is simply a fiction.
"The translational process is at the very least not understood, and to many is simply a fiction."
We have this narrative in this country that all that is required is fundamental understanding of disease, that it is a process which will inevitably happen, drugs, devices and therapeutics will come given sufficient time from those basic discoveries. And that, in a clinical trial, it will be clear what the answer is.
The fact that there is this entire area known as the valley of death, if you want to call it that-what a colleague of mine at Merck used to call the "Zone of Chaos," which was my favorite example-the public does not appreciate that this enormous area of scientific ignorance and operational inefficiency even exists. Because they're had drilled into their heads that the last line of every scientific publication is, "We're discovered X and expect that in 3-5 years there will be a drug."
What are the implications of this? The public doesn't understand why diseases still exist if we've had the Human Genome Project for 10 years, or why drugs are so expensive. If this is just a process like the night follows the day, why could drugs possibly be that expensive-it's not that hard. Why is NCATS even necessary?
"The fact that NCATS was formed in the first place, found to be necessary at all as an entity, shows you that no one was focusing on this problem."
This is a much bigger problem that I expected when I took this job on. It's an area of public education, or scientific education, and an area that's critical for us to understand. If you don't know a problem exists, you don't address it.
When I thought about this at a more philosophical way, I thought, "Wow-doesn't that make sense." The fact that NCATS was formed in the first place, found to be necessary at all as an entity, shows you that no one was focusing on this problem. The general scientific principles of translation and the operational principles of translation… nobody was focused on that.
RF: And If I recall, this wasn't even something pushed for by legislators. It was primarily an initiative spearheaded by NIH Director Francis Collins, right?
CA: Well, it actually came out of the science management review board, which is the sort of board of directors for NIH, but yes; it came as a scientific imperative for NIH to do in this sort of push-pull way we're talking about.
But this is an issue for us at all levels. It's an issue for us for our colleagues here at NIH. It's an issue for my friends in the academic and biotech community, in the congressional community. I mean, Congress is a creature of the general public. If the general public doesn't understand it, the Congress isn't going to understand it either. I think we have a big job to do, scientifically, operationally and culturally, to solve this translational problem.
"NCATS is not going to do it alone."
And NCATS is not going to do it alone . But I believe we will succeed if we do it as we're doing it as a team effort with others who see these problems.
RF: Thank you very much for your time, Chris.
CA: Thank you.
Miss parts one and two of this interview? Find them here: (Part One) (Part Two)