Transcript
Speaker: Well, hello folks. Welcome to the Trials and Tribulations podcast from UNC School of Medicine's Clinical Research Alliance. This is episode two. I'm Michael Sledge, co-host and vice president and the chief business officer of the CRA.
Speaker: And I'm John Buse. I'm the other co-host. I'm a professor of medicine and I have been conducting diabetes clinical trials for the last 30 years. And I see we have a familiar guest with us today.
Speaker: Hi, everybody. I'm Nick Shaheen. I'm a gastroenterologist and I am the director of NC TRACS, which we're going to talk a little bit about today, the Translational Clinical Science Institute here UNC.
Speaker: Yeah, so just a welcome back, Nick. For those, John, before toss it back to you, for those who who didn't catch episode one, Nick was our very first guest ever on Trials and Tribulations, and now he's our first two-time guest. So I guess like the cold open stuff and Saturday Night Live, Nick, you you can we'll have to have you back for multiple times on this stuff. so this bill This bill is going to kill you guys by the time we're done with it. Yeah.
Speaker: yeah So this episode is entitled The Multi-Million Dollar Team Sport. So clinical trials are very expensive, very necessary. It's not a sport. ah What we're doing is improving human health, but it is very expensive.
Speaker: And that brings us to what we asked Nick to come talk to us about today, which is the science of translational science. And what I mean by that is we call the process of taking an idea ah or maybe an observation that was made in an animal or in a cell and moving it to something that ends up improving human health, ah a drug or a device or some process. We call that that that that series of events, translation, ah going from an idea to a product fundamentally. And the process of developing a particular product for a particular disease state, we call that translational research.
Speaker: But there's also this notion of translational science or the science of studying how to do translational research better, how to do it more efficiently, how to do it faster. And that's what we're going to have Nick talk to us about today because he's the director of the North Carolina Translational and Clinical Sciences Institute, which is part of the national CTSA program, Clinical and Translational Science Award program, an NIH grant ah provided to approximately 60 institutions across the United States.
Speaker: So, Nick, welcome. Before we let Nick turn loose, I have to do our disclaimer. So, remember, folks, the show is educational.
Speaker: We hope it's informational. We hope it's entertaining as well. But we're not providing medical advice here. And as both our good doctors here would say, you should consult a physician and not... ah let us take medicine into your hands or however you want say it All right. Back to you guys.
Speaker: So Nick, let's start off this discussion of NCTRAC, the Translational and Clinical Sciences Institute, ah with basically what is it and what role does it play at UNC and what role does it play nationally in this CTSA network?
Speaker: Terrific. Thanks, John. um That's a great question. It turns out that about 25 or so years ago, the National Institutes of Health said, you know, gosh, we we need a better way of doing clinical and translational research across the country in a coordinated fashion.
Speaker: Since World War two All of the big research institutions in the country have been getting federal funding and doing great research, but it wasn't really very coordinated.
Speaker: And certain places might be actually doing very similar trials to other places. Or if you wanted to do a trial and wanted to involve, let's say, 10 large places, that could be very difficult and time consuming.
Speaker: So this idea that we should have a consortium of large research institutions who are working in a coordinated fashion on important questions that would in fact would affect a lot of people and we would be able to capitalize on their resources in a fashion that would let us really be able to answer big questions.
Speaker: And that's where this whole idea of the Clinical and Translational Science Award or CTSA awards came from. And like John mentioned, now there are about 60 or so big institutions of the country, most of whom names you've probably heard, places like Harvard and Dartmouth and Yale and Johns Hopkins. And UNC is lucky to be one of those 60.
Speaker: And each of these institutions is called a hub in the CTSA web. And the basic idea is that these groups are going to work together to answer a portion of questions and to share resources.
Speaker: un UNC's hub has been around for greater than 15 years. um So we got in fairly early on in this process and it's been continuously funded till then since then.
Speaker: And every year we receive a fairly sizable amount of money to help stimulate clinical and translational research, not just on our campus, but at NC State and North Carolina A&T, who are partners in this enterprise.
Speaker: um And What do we do with that money? Well, some of that money goes towards supporting researchers who are asking really interesting questions. A lot of that money goes to what we call infrastructure or making research possible on campus. And that's things like, um let's say you want to enroll a patient in a trial and that patient needs a heart tracing, an EKG, and they need a blood pressure and they need to get an injection of an investigational drug. they can come to the Clinical and Translational Research Center, which is essentially a a clinical place that's built just to do research studies.
Speaker: And they can be seen by a nurse there. They can have a technician take an EKG of them. They can get all these other services done that support the research of the investigators.
Speaker: We help with regulatory support. um We help develop proposals. So let's say you've got a great idea, but you don't know how to ask the federal government for money. We have people who are really good at putting together proposals so that they can make your idea look really special because the way the government gives out money for research is a competitive process.
Speaker: And it's a bit of a mother may I process. If you don't ask for it right, you don't get the money no matter how clever the idea is. So that's what proposal development does. There's a lot of other different facets that TRACS does that can support scientists. But the basic idea is we're helping, number one, pick some of the best science and fund some of it, especially as John alluded to, the science of doing science, which sounds like a crazy idea when you first think about it, but is actually very rational. For instance,
Speaker: um Let's say you want to do a study that requires a blood draw, but you want to enroll people that are in rural areas. Well, can you figure out how to get blood from a patient that doesn't come in? You know, can we, could we for instance, put a patch on their arm that gradually leaches blood out of them, which by the way, the answer is yes.
Speaker: um Well, that... That solution, sure, it's your solution, but you just solve 10 other people's problems too. And now they can get blood from their patients for their rural study on heart disease or their rural study on arthritis. And that's a nice example of the science of doing science.
Speaker: So we want to make those things possible. I think another real strength of this whole idea ah that the federal government came up with and was the idea of creating this network. So our people who, for instance, have a facility where you can do clinical research at UNC or our people that help with biostatistics are linked through this consortium of 60 other CTSAs with the other 60 centers people. And so we share ideas, we think about, well, what's the big problem we keep running into and we try and solve them together.
Speaker: ah So it's really ah it's really a very powerful engine. Yeah, and I'm happy you raised that aspect of it because in modern research, no one can be an expert of everything.
Speaker: as As John was explaining, this idea of translation, which means you have a great idea on how to make somebody better. That has to go through an initial process, which usually involves a lab, may involve injecting it into mice. Who knows how you're proving initially that it works?
Speaker: But then it's going to go to a clinical trial. The people that injected the mice almost never know how to do the clinical trials. The people that did the clinical trials almost never know how to do what's called implementation, meaning, okay, it worked, it worked in the clinical trial. How do we actually get people to use it on a day-to-day basis? There's a whole science of that.
Speaker: um And people that did the clinical trials like myself, are not expert at that. So you have all of this knowledge you have to have. And they're just like there's a number one in everything in the world. There is the number one person for implementation for a diabetes intervention.
Speaker: There can only be one number one. And that person has a very low chance of being at your place. But there's a very good chance that that number one may be in one of the top 60 places in the country. So you can get to the number one because they're in your consortium.
Speaker: So it really does allow you to parlay this vast amount of knowledge and expertise to answer a very focused question.
Speaker: Yeah, Nick, this is picking right up on what we talked about in the last episode, right? About... ah We debated, is it a village, is it a city? i think we're moving up to something, even a metropolis maybe, because you know we we're talking about all these people that are actually doing the science behind the science that leads to the research itself. So I think our community just got larger.
Speaker: A metropolis of nerds, yes. I think that that's exactly right. Translational research nerds. um So ah the maybe you could get into a little bit more detail. I remember that there was a tagline ah in the CTSA network, something along the lines, if you had an idea, ah the these CTSAs could basically help you ah execute a clinical clinical like trial or a research program to to answer the question that you raised.
Speaker: is that Is that accurate? And how how do you do that? I think that that is accurate, that one of the things we pride ourselves on because people have different expertise and because great ideas come from everywhere. One of the things we we pride ourselves on is having an open front door. Even if you've never had a grant before, if you have no formal training and research, um you know as long as you have a good idea, we can help you execute it from the beginning to the end. we can you know
Speaker: There's a difference between a an idea, i e I think this drug might make somebody better, and a hypothesis. which is much more specific, meaning I think in this group of patients for this period of time, looking at this outcome,
Speaker: I think that this drug will lower the chance of this bad outcome. That's a hypothesis. So getting from a general idea of, oh, insulin might be good pe for people to the idea of, oh, a GLP-1 inhibitor might decrease the likelihood that a patient dies of heart disease within two years of initiating it for this subgroup of patients.
Speaker: It's hard. It's hard to think through all those steps and and and um We can help with that. Not only can we help conceptualize, but as we talked about the last last episode, there's so much that goes into, you know, trying to do even early tests. So what data are you going to collect? How are you going to collect it Are you going to put it on a piece of paper or are you going to put it into a website? How are you going to analyze those data?
Speaker: How do you know how many patients you need for the trial, whether you can do it with 10 or if you're going to need 100? Obviously, we don't want to rack up extra cost if we can get our answer with relatively few patients. These are essential questions to answer. And there are questions that many times researchers don't do a great job of answering on their own and they need expertise from, say, a biostatistician or an epidemiologist or somebody that specializes in recruitment. How are we going to find these patients that even want to participate in our trial So there are all these different facets that you need to have a successful trial. And it really takes a lot of different expertise. Fortunately, because of the support of the federal government, the NIH, as well as support, I will mention locally here as well, um from campus and other entities, we're able to have experts at TRACS that specialize in all these areas. And if we can't help you, and by the way, there's a very good chance we can help you, but if we can't help you, we will help you get the help you need.
Speaker: That's a good segue. So, you know, for our for our on-campus people that are listening to us, you know, sometimes it's hard for them to sort out the different entities on campus. So narrowing it down, at least to our world, um you know, the CRA and TRACS are collaborators, not competition, right? So maybe me say a little bit about how you view that that relationship and what Where does it make sense for TRACS to be involved or the CRA? or or can we tell people there's a bright line for that?
Speaker: I'm glad you asked, Michael, because I think now there's confusing times, especially for folks on our campus, because we're evolving so rapidly, these institutions. The CRA has only been around for a couple of years. Now we're standing up clinical research partners or CRP. TRACS has been around for longer, but it's natural with this proliferation of acronyms and everything that people don't know necessarily where to go.
Speaker: The first thing I'll tell them, which I think is the probably the most important thing, is that we'll get you to the right place. Knock on any of those three doors in any of We're in the research business. CRA, CRP, and NCTracks are all in the research business. If you came to us with a problem that is best suited for the CRA, we're going to get you over there. You don't need to worry.
Speaker: the way that I might think about it in terms of um who you go to first, it depends on kind of the the problem that you're trying to solve or where you are in the conception of your project. If you're in very early stages and just trying to figure out what resources you need, how you might structure et cetera, I think I might knock on Trax's door because the whole range of of how to put the project together, et cetera, is available there.
Speaker: If you've got a mature project and especially if that project is going to be a project that's a multicenter project that that Carolina is going to be serving to help coordinate, but it's mature, then is where you want to go because they're going to help you with thorny issues.
Speaker: in data management and in reg, which can be very difficult, regulatory approvals and all the other things you need to do to get a big trial stood up.
Speaker: Finally, if you're doing work that's funded by industry, and let's say Carolina is going to be a site for a study, which is probably one of the most common things that we do is is be ah a member site for a larger multi-center study that's funded by industry, then you're probably headed for clinical research partners or CRP.
Speaker: Having said that, There's wiggle room with all of that. and And you can get help from multiple different places. So the only way you can really mess this up is by not asking for the help. If you ping any of us, we are going to get you to the right place.
Speaker: You know, it's interesting that, and I hadn't really thought of it this way, but each of us, CRA, TRAX, CRP here at UNC, deal with the same big friction points.
Speaker: contracting, regulatory, you know protocol development, sort of locking down data management analysis. We all do it, but in ah in a different ah scale or dimension.
Speaker: um So I do think it's correct that if an investigator or an individual with an idea comes to any of us, we we can get them pointed in the right direction. But if if you're thinking about a study ah that you kind of imagine being done here at UNC, that's it, ah then it's ah then it's probably tracks. If you're thinking about a study where you're going to lead the charge and and it's going to be multiple institutions, then the CRA is probably your
Speaker: place And if it's an industry-sponsored trial and you're going to follow the cookbook that's provided in the protocol, then CRP is the way to go. And then, you know, I think ah the thing that I'm most impressed with, the TRACS and the CRA, ah is the remarkable skills and dedication of the staff that make make these projects go.
Speaker: make these projects go Do you want to talk a little bit about that process of of how we find people and bring them up ah and then the trainings that we provide to people all across campus?
Speaker: Yeah, that's clearly the secret sauce of all these organizations. The the fact the fact that we've been lucky to recruit and retain retain such enormous talent in each of these areas is really a boon for all of the investigators on our campus. And, um,
Speaker: For many of the areas that we have been talking about, things like, you know, biostatistics or recruitment or epidemiology, um these are all their own disciplines. And they're many of the folks who are most expert are PhDs.
Speaker: And in fact, when you look on the staff of a place like TRAX and to lesser extent, but to some extent um in other places on campus as well. What you'll find is that the person that's heading up that group is PhD in epidemiology or PhD in biostatistics. and And we're so lucky as an institution to have such a wonderful school of public health, because a lot of these disciplines actually live in the school of public health. And many of these folks
Speaker: our faculty members. And we've been able to kind of pull them in. and the way it works is we pay a small part of their salary. So we'll say, we want you one day a week to work on clinical research projects with us.
Speaker: And for that, we're going to pay 20% of your salary, for instance. That might be the the kind of deal we make with a faculty member at the School of Public Health. And oftentimes because it gives them something interesting and different to do and because it lets them exercise parts of their brain that they may not be exercising in their other work, they enjoy that.
Speaker: And we've been able to maintain this group of folks over the years to provide services and to help our investigators who are really smart but may not be great experts on how to do a power calculation to figure out how many patients they need in their trial or What's the best way I've got this whole mass we've been talking in this episode, in the last episode about the amount of data clinical trial spins off.
Speaker: How am I going to analyze all of this data and make sense of it? Well, we have folks that can do that and have been doing it for years. And in some cases it over 15 years for tracks. So we' we're really lucky to have the people we have. um C.R.A. and C.R.P. are are younger, but have wonderful, wonderful staff as well. And in order to keep both our people sharp as well as to increase the level on campus of general knowledge about these topics.
Speaker: we're constantly doing education as well. That's one of our main missions. So we'll run a session on um what's the best way to recruit patients for a certain kind of trial or or how should we think about analyzing big data that comes out of, say for instance, the electronic health record um and and really help people try to think through that. So there our goal here is not only to have the expertise at our place, but to increase the expertise all across campus.
Speaker: So I think it's been a great conversation. ah you know Clinical trials are multimillion dollar team sports ah and creating the infrastructure to allow your team to function well is is critical.
Speaker: So Nick, thank you so much for coming and talking to us about about the North Carolina Translational and Clinical Sciences Institute and the role it plays here and nationally.
Speaker: Yeah, and that takes us to a couple of recurring segments we have every every episode. We're going to do two of them today, the burn rate.
Speaker: Burn rate is our quick look one specific cost of delay because as we've said before, time is money in this world. And um you know the one I want to hit on today is about contracting. We we touched on that, contracting regulatory processes and and how you know if you've got 12 institutions that are involved in something and everybody's doing it differently, how much you can just see how much time and cost that's going to add.
Speaker: um John, maybe I think you know a little bit about this topic. Tell us a little bit about the accelerated clinical trial agreement. And I think that came out of the CTSA, NC TRAX kind of world, didn't it?
Speaker: It did. It did. So it's a genius idea ah that in many ways, you I never thought it would come to pass ah because every institution's lawyers are so nitpicky about the agreements that they make that I thought it was impossible that dozens, and it may even be 100 now, institutions, including multiple big pharmaceutical companies and device manufacturers, came together and came to a sort of boilerplate agreement for conducting a clinical trial.
Speaker: And I can tell you that when ah ah a sponsor has been in a big hurry to get a clinical trial moving forward, and we talk about the usual weeks to months delay that contracting takes. And i mentioned to them, well, you know, we have this prearranged ACTA, ACTA, the Accelerated Clinical Trial Agreement, ah ah where if you're willing to agree to these terms, the university will sign it in a matter of hours to days. There's basically no negotiation that happens. And I do think that moving forward, these kind of agreements would be more common because of the thousands of contracts I've been involved in, only one never got signed, meaning that the parties could never come to an agreement on all the different issues, but all the rest got signed. So there is a path forward. Might as well find the path now instead of spending months arguing about the details.
Speaker: Well said. Nick, any comments on that one? No, I think that's spot on. Yeah. Okay, let's do myth versus fact then.
Speaker: I'm going read the myth. And Dr. Shaheen, you're up again this time and you're going to call it. All right, so myth or fact, research infrastructure is overhead. it is a cost center that slows scientists down. Good infrastructure is just the opposite.
Speaker: The... You're going to have to have certain aspects of organization in place before you can do a study regardless.
Speaker: You don't want to be doing everything you're doing for the first time. You want to have a well-greased pathway, similar to what John was just discussing, to accomplish these in the least time possible. Money is time when it comes to clinical trials, and it's actually an ethical concern as well because you're delaying potential cures for people and you don't want to have useless time that is accruing additional costs. So good infrastructure is about the best investment that a research institution can make.
Speaker: Awesome. John, any comments on that before you tease us on the next episode? ah No, not all. That is spot on. Again, Nick, thank you so much for coming to talk to us. You know, the the clinical trials business, the translational research process is a multimillion dollar ah team sport and the infrastructure is critical. Your leadership at ah North Carolina Translational Clinical Sciences Institute has been extraordinary. Thank you so much for what you do for our institution and for the country in that regard.
Speaker: um and Next episode, we'll be talking to another leader in the UNC system about decoding the acronym SALAD. You heard a bit of that today, TRACS and CRA and CRP, but there's FDA and IRB and ah many, many other acronyms that we'll be talking about on the next episode.
Speaker: Is there an ASAP one? I don't think I've run across that one. I haven't researched it, but... um Hey, Nick, thanks. Any final words from you before we sign off for this time? Really enjoyed it Thanks for inviting me, guys. Yeah, i look we look forward to having you back.
Speaker: John, good to see you again, as always. We'll see you folks on episode three. Thanks so much.
