Transcript
Speaker: Welcome to the Trials and Tribulations podcast from the UNC School Medicine's Clinical Research Alliance. I'm Michael Sledge. I'm the co-host and I'm the Vice President and Chief Business Officer for Sierra.
Speaker: And I'm John Buse. I'm the other co-host and I'm a professor of medicine and a diabetes clinical trialist. And we have a guest today. We do. Dr. Nick Shaheen. Hi everybody.
Speaker: Yeah, I'm Nick Shaheen. I'm gastroenterologist here at UNC Chapel Hill and have been for 30 years. I'm also a clinical researcher and do an awful lot of the work that we're going to discuss today.
Speaker: I think what's so important about clinical trials is they're the necessary methods and processes that bring us medications and devices that improve human health. Without them, there would be no advances in the ah treatments that people receive from their providers.
Speaker: um So they accomplish amazing things, and particularly if we think about what's happened over the last decade and with regards to the advances in medical science.
Speaker: um But what often is missing from the discussion is that this is the ultimate team sport. There are thousands, if not tens of thousands of people involved in every clinical trial program that successfully brings a product to market.
Speaker: And the vast majority of those people go unrecognized and even their roles are are not understood. So we're here today to talk with Dr. Nick Shaheen ah ah regarding this issue.
Speaker: Michael, I think you have some disclaimers. I do. Let me get through this disclaimer and then I'll kick it back to you, John, and you can get us started with Nick. So just remember, folks, this show is informational and educational.
Speaker: It does not provide medical advice. all right, John. So we thought that Nick was the perfect guest for this show. Not only is he ah glib and brilliant, ah but he also has ah been through the process of bringing both drugs and devices to the US marketplace from the essentially the inception of the idea all the way through FDA approval and marketing. And so with that, I'll turn things over to Nick. Why don't you tell us just a little bit about ah how you got into this space and you know maybe examples of of how the process is going.
Speaker: Thanks so much, John. I'll start by seconding exactly what you said a minute ago. This is not esoteric. When you woke up this morning, there's a good chance you went to the sink and you took a pill. That pill was almost certainly ah result of a clinical trial that resulted in FDA approval, and now it's impacting you every day.
Speaker: Or perhaps your uncle had a heart attack and got a stent put in. Guess what? That stent also underwent the same rigorous process that we're going to discuss today. David This touches virtually everybody, this is not a piece of minutia and this has never been more important, because there are some important changes that are happening in the way that clinical trials are being run in this country that I hope we touch on at the end.
Speaker: David My journey has started with brownie in motion I banged into this by accident I didn't know that this is what I was going to spend my life doing there were some. more senior people in my training programs, both at University of Chicago and at University of North Carolina, who are involved in this kind of work, and and I kind of got bitten by the bug.
Speaker: The area that I chose to work in, I'm a gastroenterologist, when I showed up in training, the biggest question was what to do about colorectal cancer. or that would That's a huge cancer killer in the country. Probably the second biggest question was what to do about heartburn and the precancerous condition that goes along with heartburn called Barrett's esophagus.
Speaker: And at that point, it was known about a little bit, but people didn't know exactly what to do about it. There was a lot of hand wringing, but we really didn't have any great ways of treating it. What we did know was that it was associated with this deadly cancer, esophageal adenocarcinoma, and that that cancer not only was it deadly, but it was rising hi in huge proportions in incidents in the United States for reasons that weren't clear us.
Speaker: So this seemed like an interesting area in which to work. So I began and in my early work, I got to work on some of the drugs which are commonly used now for acid reflux, for instance, omeprazole, lanzoprazole, many of these drugs, ribiprazole, these drugs that are now available over the counter that you see by trade names like Prilosec, Prilosec, The i got to do some of the early work on those drugs, and I really learned a lot from those trials, which were huge, very well done trials. And to John's point, it takes a village to do one of these trials and it takes a relatively large village. Village is probably the wrong word. It takes a small city.
Speaker: And we're talking about, first of all, the participants, which in these trials sometimes numbered into the tens of thousands of people at each site where these were being run, there were probably 50 or more parties involved. And each site was run by what's called a principal investigator or somebody who's overseeing all of the activity at that site.
Speaker: But in addition to that, just multiple, multiple study coordinators, all sorts of folks that were gathering um the data, and it was all being rigorously um taken down in what's called a blinded fashion, meaning that nobody knew if the patient was getting the investigational drug or the comparator drug. some of these In some of these trials, the comparator drug was what's called a placebo, meaning that it was essentially, there was no active ingredient. and Hey, let me, if I could jump in just a second for our our viewers or listeners who might not be as versed as we are in some of this stuff. So before we go further, tell people what you mean by a site. Like, what is the site?
Speaker: Is that the place where the patients are going to go to see their doctor? Great question, Michael. And a site means nothing more than an institution that has contracted either with the company or with a third party to help run the trial.
Speaker: The patient themselves may never go to the site in that the, especially nowadays in the days of what we call decentralized trials, sometimes the patients never go to the site.
Speaker: In these older trials that I'm discussing, the patients did actually come to a place, say, for instance, like UNC, that may have contracted usually with the company that's developing the drug.
Speaker: Okay, great. Sorry to interrupt. I thought that just might be. No, not and not at all. um So these trials have certain standards that have to be adhered to in order for them to be considered by the FDA as adequate evidence that the drug should be approved.
Speaker: Okay, and turns out that although there are rules and the FDA kind of lets the companies know, you can get fairly far along in this process and spend literally millions and millions of dollars if you're a company. And the FDA will say, you have not lived up to our standards or your data are not strong enough after putting in tens of millions or sometimes even hundreds of millions of dollars into investigating a drug. The data are just not strong enough.
Speaker: for our country to approve this drug. So it's a laborious process and it's high stakes poker. um But it's a wonderful process with respect to both protecting patients, okay, because the bar is high, and also for maintaining quality of the evidence because it'd be very difficult for anybody to monkey around with these trials just for profit.
Speaker: so So it has a lot of virtues. Protecting patients and quality. John, you got some questions for him on that? Yeah, I mean, one thing you you started with the the the city, the small city that needed to be engaged to get one of these drugs or devices across the finish line. And you mentioned ah tens of thousands of participants and each site might have 50 people, the principal investigators, study coordinators, ah people that are doing ah invoicing and billing, you know all kinds of different job descriptions.
Speaker: But then there's maybe 50, 100, 300 sites. And then on the sponsor side, the company that's developing the drug, an equal small army of individuals that are involved with all the different aspects of the trial. So it literally does add up to tens of thousands, if not hundreds of thousands of people for one of these big clinical trial programs.
Speaker: I just wanted to clarify that. Yeah, and all this data is generated, believe it or not, there's so much data generated for a new drug application that it literally is brought to the FDA in a semi truck.
Speaker: That's how much data, or at least in the old days it was. now Nowadays, of course, it goes via a few electrons flying in the air, but but when when those big blockbuster drugs that I mentioned that I got to work on early in my career went to FDA. They went to FDA and semi-trucks those applications.
Speaker: So ah a question for you, Nick, or maybe John, you might want to jump in here too. And I trust that my cardiologist is not watching or listening to this particular episode, but um I like sausage. It's kind of tasty, right? And in our title today, we're talking about the sausage, the science, and the impact. So a lot of times when people use this phrase, what is it? Seeing how the sausage is made, right? It's kind of this euphemism or this this phrase for like, you know, you don't really want to see how sausage is made. You really like the end product, but don't go back and look at it. So for both of you, because you're a very accomplished clinical trialist,
Speaker: What does that mean for you when when we talk about the sausage and do we want people to understand this or is it just too much to put on people to try to figure it out? You know, Michael, first thing I'll say is maybe the reason you have a cardiologist is because you like the sausage, but we can pick it up another time.
Speaker: The second thing I'll say is that even though there are a lot of parts to this, It actually is something that I think it's important that consumers are aware about, because even though there are a lot of steps to it and it isn't all quite always as pretty and clean, it it's actually very admirable, I think, the way we rigorously test these drugs. And in fact, I think that some of the skepticism about treatments and and in general about, um you know, is this safe for me would actually be allayed if
Speaker: folks understood a little bit better what a drug, for instance, has to go to or through our device to get approval by the FDA and get to be used. So while I think you're absolutely spot on right that there are a lot of moving parts and maybe some of it gets messy, patients take the drug and then wander off, they don't come back for their evaluations and all the crazy things that people do.
Speaker: In the aggregate, I think it's a terrific system. I think that the more transparency we can apply to it, the better off we are. yeah And I just, I love the ah the way that you ah raise the issue that maybe you want don't want to know the details here about the sausage making, you know, a little bit like how much pig snout is in my sausage kind of thing.
Speaker: there And every trial has its little hiccups. And the FDA does an incredible job of digging into literally hundreds of thousands, if not millions of bits of data, you know, looking for the sausage snouts. And, you know, there are mistakes that are made. ah You know, people are people. ah Participants, that's what we call the patients in the trial, ah ah don't always do exactly what they agree to do. And there are investigators, unfortunately, that from time to time don't do exactly what they're supposed to do. And the FDA takes that all into account.
Speaker: and is ah really careful to make sure that the sausage of the finest quality.
Speaker: Well, do you want to tell take us through one trial? You know, something that started as an idea. And I know some of these drugs, you know, the process goes many years before they even start talking to doctors. Devices are sometimes a little bit easier to understand the process.
Speaker: Yeah. like Let me tell you about a device. um I was walking around our national meeting um one day and going from session to session. And this guy I'd never met before walked up to me and said, we think we figured out a way to cure Barrett's esophagus. Come to my hotel room.
Speaker: And this is literally what happened. And he looked kind of shady. And and i didn't know if that was really a good move. But in my youth, I said, what the hell? I mean, let's go see what what he's got.
Speaker: So I went up to this hotel room. And this guy had pieces of steak on his bed. And there were engineers in there. I could tell there were engineers to the tape in the middle of their glasses.
Speaker: And they were using this device to burn the steak. And just to give you some idea till now, the only thing we ever did when we found this pre-cancerous conditions, we sent them off to surgeon.
Speaker: And the surgeon, if it got bad enough, would cut you here, cut you here, take out your food tube, pull your stomach up through your chest and reattach it under your chin again. And that's how we got rid of Barrett's esophagectomy. That's the only It's called esophagectomy. It's the only way that we had to get rid of it. And it was every bit as unpleasant as it sounds.
Speaker: And... what these engineers were working on was a way of getting rid of the Barrett's without removing the food tube that could be done as an outpatient and that would allow healthy tissue to grow back in.
Speaker: And they showed me the initial prototypes of it. And i said, you know, this is really interesting guys. They were able to get ah perfect depth of burn that would get rid of the inner lining where, which was where the pre-cancer was, but leave the rest of the, the,
Speaker: esophagus. But I said, you've got to be able to deliver this through an endoscope and in 200 milliseconds, you know, um less than a blink of an eye because patients do funny things like move around and cough and breathe. And we just can't have them. They can't sit still indefinitely to get this energy delivered.
Speaker: And I never thought I would see them again. And they roll this thing into my endos suite a few months later. And I'll be darned if it didn't have all of the exact specifications that I told Long story short, we took that through clinical development, early trials, and then a big, what we call a pivotal trial, which is the trial that we plan to take to FDA in 19 centers in the country.
Speaker: And we showed that we could decrease the risk of cancer in Barrett's by 95% by giving these treatments. And After we published that, those treatments are now done 100,000 times a year in the United States. I did three of them to different patients this morning.
Speaker: None of those patients are likely to ever lose their esophagus. So this was really impactful. I didn't see it coming. i didn't think it would work when I first saw it. I didn't even think it was the best thing I saw that day at the meeting.
Speaker: which goes to show you that you just never know how things are going to play out. But that whole process, which is is called ablation or endoscopic eradication, became the standard treatment for Barrett's with precancerous change in it.
Speaker: um And it wasn't, you want to talk team sport, 19 centers, hundreds of of participants, great people at the company constantly iterating the product, giving our feedback, do this to it, do that to it, that didn't work, let's try this. Until we got it into the place where we could really rigorously test it.
Speaker: um You know, and from beginning to end, that first interaction with that guy was was seven years, probably six, seven years before patients outside of the trial ever got to use the device. And that's pretty accelerated.
Speaker: that that number can easily go up over 10. Yeah. yeah And, you know, here at the Clinical Research Alliance, we like to focus on operations. Can you think of, you know, I hate to put you on the spot, you maybe haven't thought about it in a long time, but can you think of stumbles that could have threatened the whole project or miscues that set you behind for weeks or months? Yeah.
Speaker: Oh my God, thousands of them. If nothing else, i mean, one thing that that the Research Alliance does very well is regulatory work. Just getting all of the agreements in place to be able, you know, you don't even think about this when you hear these stories, but in order to share data with each other, in order to share devices across um sites, in order for us to be able to give our information about our patients, all this time we're we're jealously guarding our patients' information. Just because you're in a clinical trial doesn't mean that you give carte blanche for us to send your medical information all over. That stuff is held just as safely as if
Speaker: We were giving you regular clinical care. So all of these different facets of this trial are have to be adhered to.
Speaker: And then when we generate the data, we don't just write it down on a piece of paper and hope for the best. Now, it's all there's there's complex data management. We actually input data into central database.
Speaker: that are constantly taking data from all of those sites from all over the country. So the amount of infrastructure and time and potential mistakes that can be made and are made routinely is staggering. And that's why it's important for organizations like the CRA and NCTracks, which is a place where I work, to exist because these places have developed expertise in these various support mechanisms that are essential to completing clinical trials.
Speaker: Nick, that that is, um I wish I'd heard that story a long time ago about meeting the guy in the hotel. at that That's amazing how things transpire. So as we're getting close to wrap up here, so we're done with barrragus Barrett's esophagus. That's cured now. We can take that off the list. Is that what you're telling us Actually, no, is the answer to that, because most people who have Barrett's don't know they have it. And that's definitely a topic for another one of these about thinking about when you need to come in when you have heartburn. And I'm not giving medical advice, as you said. If you have chronic heartburn, talk to your doctor. that That wasn't medical advice. That was just an opinion that I just said.
Speaker: But do it. Right, right. Yes. Mark continues. Yeah, so's fine somewhere somebody's working on the cure for Barrett's, probably.
Speaker: heard to that All right, John, any last questions you've got for Nick for today? and No, are are you still heavily involved with old fashions?
Speaker: i It's bad for your esophagus, John, I don't do that anymore. You mean like old fashioned medicine, right, John? Yeah, that's right, yeah. A shot of bourbon's good for what ails you, that's for sure.
Speaker: All right, well, Nick, we have some recurring things that that we go through here at the end of our episodes. um The first one is called the burn rate. So it's time for the burn rate.
Speaker: And that's our quick look at one specific cost of delay, because as we have touched on here in this world, time is money. So here's today's. A multi-site trial sitting in contracting review for four months while the site's legal and compliance teams loop in procurement, sponsored projects, risk management is a bit more serious than a paperwork hold.
Speaker: Your study coordinator is ready. The IRB approval is good to go and the labs are prepped, but none of the site's patients can enroll yet. At most academic coordinating centers, contracting is the last gate before the site goes live, which means delays here compound every other delay upstream.
Speaker: Fair to say you've experienced that one before? This is no joke. to Every day in the field for a large clinical trial can literally mean hundreds of thousands, if not in some cases, millions of dollars. So literally a day's delay, a week's delay,
Speaker: is catastrophic. And this is so common, what you just described. And I think that's one of the reasons why organizations like the so CRA are so important to kind of grease those skids and and and try to develop the pathways to allow quick approval of these contracts.
Speaker: Yeah, well said. in it And I have to say, i mean, I've been working in this field for over 30 years, and it's always been the rate limiting step.
Speaker: And our institution, I think every institution on on the planet is working on how to do this. better, faster, ah less ah less stumbles along the way.
Speaker: um And, you know, it's absolutely essential we do this. It's such a waste of time to spend all your all your time arguing about things that fundamentally you're going to agree upon. It's just a matter of finding the way to the agreement faster.
Speaker: Yeah. Again, well said.
Speaker: Okay, myth versus fact. I'm going to read the myth and our guest is going to call it. So Dr. Shaheen, you're up. Myth or fact, a trial's impact is measured by whether the treatment works.
Speaker: Total myth. Total myth. In fact, I think some of the most valuable clinical trials are those that debunk treatments that we give without evidence.
Speaker: You know, one thing that we haven't set up till now is that for many of the decisions your doctor makes in the average day, he or she is guessing because there aren't there isn't a good clinical trial for every question that you need answered.
Speaker: It's a gift from God when a clinical trial comes through. And even if it says to you, you know, that thing you thought was right ain't so right. And that treatment that you've been giving, it's no better than a sugar pill.
Speaker: So I think that a negative trial many, many times is just as valuable or occasionally more valuable if you really believe that our primary dictum is to do no harm than a positive trial.
Speaker: Yeah. John, any comments or reflections on that? that's absolutely true. Yeah, you know, and we were talking earlier about transparency in the sausage. Like, this might be one of those really key things we'd love for the public to know more about because, you know, I don't know how many times I've heard a friend, a relative, somebody, you know, just bemoaning the fact that the latest thing they just saw or read in the news was about this thing that was supposedly, you know, it's okay to drink two glasses of red wine a night. Well, no, it's not. Hold on. And so it's sort of...
Speaker: You know, I think for some people that calls them the question of the validity of what's going on here. So more transparency here is probably not a bad thing.
Speaker: Okay, game time. This is where I tie a moment in sports to clinical research. So think about a championship team that does not have the flashiest roster.
Speaker: They win because everybody knows their assignment and executes it the same way every night. A multi-site trial works the same way. The science can be sound, but if 12 sites are each running the protocol a little bit differently, the data is not going hold together.
Speaker: The win comes from alignment, not just talent. That's absolutely correct. You know, a great game plan in this context requires all the sites to be perfectly aligned, but also all the staff at the sponsor ah as well.
Speaker: And then every player for, you know, using the sports analogy, every teammate at every one of the sites has to be aligned. I mean, one person can...
Speaker: completely upset the apple cart.
Speaker: Yeah. Nick, any reflections from you on that? No, I think that's spot on. So here's the personal note for for me today, certainly, and I'm sure for Nick as well, who's worked with John for a long time.
Speaker: We're recording this episode on June 30th 2026.
Speaker: This is John Buse's last full day on faculty here at the University of North Carolina at Chapel Hill. I don't think people understand as well as they should the impact that this man has had on this university and has had on the the type of topics that we're talking about here. So John, I know you're gonna continue to be here with me as we do this podcast going forward.
Speaker: I won't see you around the campus so much, but it has been a joy and a privilege to work with you over the last nine years. It's been a great run. ah Working in clinical trials has been just a delight for me. And I've been very fortunate to have a great team at a great university and ah look forward to many more great things coming out of the the CRA and TRACS, which we'll talk about more with Nick on another episode.
Speaker: Nick and I go back to when I was a resident and he was a medical student, I think. That's exactly right. And, you know, Michael, well said, couldn't be better said, you know, John's contributions not only here, but to the field of diabetes, which is his major area of research are monumental.
Speaker: Grabowski, I don't think it's hyperbole to say that patients are treated the way they are treated and living longer today with diabetes than ever before. David Grabowski, in large part of the work that john and his colleagues have done over the years it's hard to find an important trial and by bees that he doesn't have his fingers on. what enormous, enormous contributions. And for me personally, what a role model and a mentor, um you know, I can't say enough good things about his career and what he's been able to accomplish. Well, I always just wanted to be the Nick Shaheen of diabetes.
Speaker: That was my goal in life. I think you nailed that by week two. All right. I think we're saying farewell to Dr. Shaheen, but not goodbye. Right, John? You want to tease us on the next episode?
Speaker: Yeah. So the the next episode will be entitled The Multimillion Dollar Team Sport. And we'll be talking with ah Dr. Shaheen about some of his works with the North Carolina Translational and Clinical Sciences Institute and how that's transformed research both here at UNC and across the across the world.
Speaker: All right. Nick, any last words from you for today? This was a lot of fun. Thanks for having me. Yeah. Thank you so much for being here.
Speaker: All right, folks, that's it. That's a wrap for episode one. We'll back at you shortly with episode two.
