Announcer:
0:00
Welcome to MedEvidence! where we help you navigate the truth behind medical research with unbiased, evidence-proven facts. Hosted by cardiologist and top medical researcher, Dr Michael Koren.
Dr. Michael Koren:
0:11
Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence!, and we have a really special podcast today. I always enjoy it when I have a kindred spirit on with me and I'd like to introduce Dr. Doug Denham, who is a clinical investigator, a fellow CPI, and he's going to explain what that means. It's a very special designation that he and I share and truly somebody who has been involved in this industry, like I have, for many years and has tremendous insights based on that experience. So, Doug, welcome to MedEvidence!
Dr. Doug Denham:
0:44
Well, thank you, pleasure to be here.
Dr. Michael Koren:
0:46
Yeah, so Doug works out of San Antonio, Texas, and he's part of a site there that's really one of the premier sites in the entire country, a great example of an organically developed site that has become really one of the pivotal places where great clinical research is done. And I had the privilege of visiting you just a little while ago and I was super impressed by your facility. Magnificent 20,000 square feet, covers everything from phase one through phase four. You name it, you're doing it and just super impressive. And I also felt good and felt redemption when I saw you run around just as much as I do day to day. We're not desk workers, we're not sitting around looking at our emails, we're out there hands-on. So I truly enjoyed seeing that. So thank you for inviting me out to your facility, and now it's my chance to invite you into our virtual facility. Well, I appreciate that. So, Doug, we're going to talk today about the challenges of retention in clinical trials, but before we get into that detail, tell us in the audience a little bit about yourself.
Dr. Doug Denham:
1:52
So I'm a board certified family medicine doctor. I was in private practice for about 20 years and then started doing research about 2006 and have been doing it full-time probably since about 2010. I had a nursing home practice at that time on kind of on the side that allowed me to kind of keep my fingers in that side of medicine. But I've closed the practice down now and doing this completely full-time. So it's a nice transition, I think, for me. I still have the patient contact, like I did with the clinic, but I'm also on, you know, cutting edge of medicine. We're seeing the new drugs as they come out, new devices, so it's exciting and it's enjoyable. Pace is a little bit better but still busy, but yeah I enjoy it. Beautiful.
Dr. Michael Koren:
2:49
Now, So one of the marks of somebody that's really dedicated to being a principal investigator is the CPI designation. Do you want to explain that to the audience?
Dr. Doug Denham:
2:57
Certified Principal Investigator and it's a certification where you have to have a certain amount of experience and training to reach that and you have to take a test and to show that you know all these things. And it's not just about seeing the patient and adjusting their medicines and those kinds of things. You have to know all the other aspects of research, the regulatory stuff, the federal stuff, all those kinds of things. The good clinical practices, how to take care of the patients and your responsibilities as an investigator with your patients. So I think it gave me a little more in-depth appreciation for what my role as an investigator is and also the responsibilities that are there that I think some people may not really understand until they kind of dig into a little bit more.
Dr. Michael Koren:
3:52
And you have to take a board exam and pass a pretty long board exam to become a CPI, a certified principal investigator, and I recall it was reasonably challenging. It wasn't trivial in terms of things we're asked to know.
Dr. Doug Denham:
4:06
No, yeah, they want to make sure you know what you're doing in terms of conducting a study and trial on those things, your responsibilities.
Dr. Michael Koren:
4:14
So what's interesting is that the CPI exam gets into a lot of elements of good clinical practices, or GCP, which is part of federal law, and those are the kind of things that investigators need to know very well. For example, how to report an adverse event, what's a serious adverse events, what's a SUSAR a Suspected, Unexspected Serious Adverse Reaction? So all these kind of alphabet soup things that we learn over time and it's quite extensive. But the one thing that really doesn't get covered, which is a pretty big area in these CPI exams, is how to approach a patient about clinical research and how to keep people engaged in clinical research. So you mentioned, off air, that you are very interested in obesity and just came back from an obesity conference. So maybe share a few things about the obesity conference and then let's talk about some of the challenges of doing obesity research.
Dr. Doug Denham:
5:16
So yeah, the conference was really interesting. It has folks from around the country and around the world there and they're not just physicians treating obese patients, they're the people doing the bench research and doing all these things the preclinical animal studies and mapping and you know, it was a very in-depth conference and I felt very excited some of the things I learned from it. But there's a lot of new medications that they're looking at in addition to the big ones
Dr. Doug Denham:
5:49
Right now, the GLP-1s are hot, but there's other stuff coming down the pike that may be just as effective without some of the side effects and issues that we see with the GLP-1s. So I think there's a lot of good things out there, so there'll be lots of stuff coming at us in the next year or two that will be interesting to do study-wise.
Dr. Michael Koren:
6:09
Yeah, so the GLP-1 analogs, or agonists, are such a fascinating class of drugs. As you recall, they were originally developed for diabetes and these are drugs like Ozempic or Mounjaro, the two most common in the US. And these drugs were originally developed for diabetes and the FDA was concerned that there were safety issues for cardiovascular patients. So I remember doing my first GLP-1 agonist as a cardiologist and people were looking at me as like, why is a cardiologist in the room for this drug for diabetes? And at that point we didn't know about the weight loss properties particularly, but we did know that these drugs lowered glucose. But the FDA was concerned that maybe some of these drugs would have unintended consequences that would affect cardiovascular health. So, lo and behold, we do these studies with these drugs and these were long-term outcome studies that required people to stay in the study over a period of time.
Dr. Michael Koren:
7:03
And not only do we find that they were safe for cardiovascular patients, but we actually found that we were reducing cardiovascular events and lowering their blood pressure and lowering their cholesterol, in addition to losing weight. So it's a great example of unintended consequences. Were you involved in some of those studies back in the day?
Dr. Doug Denham:
7:24
Yeah, we did some of the earlier ones too. Yeah, they're challenging just because, like you said, they're longer studies than the normal studies that we run. So it's a whole new issue to deal with when you're doing those kinds of trials.
Dr. Michael Koren:
7:35
Okay.
Dr. Doug Denham:
7:35
Keeping the patients involved for three, four years sometimes.
Dr. Michael Koren:
7:39
Absolutely so. Now I'm going to ask you a question that's not on the board exam and I think you're up for the task, all right. All right, so you're an investigator working in maybe San Antonio, Texas maybe, for example, and you're involved in a study and somebody in your community is really excited to get involved in this study because it involves a GLP-1 drug and he's in the study for six months and he hasn't lost any weight. But this is a three-year outcome study and this guy is really getting irritated with you and he's saying, hey, I wanted to do this to lose weight and I'm not making any progress. He says, doc, I think maybe I want out of this study. How do you approach somebody like that? That's a challenge.
Dr. Doug Denham:
8:23
It is a challenge, yeah, so, um, at the beginning of the trial I spend a lot of time talking with the patients before we even get them into the trial, talking with them about outcome trials and how this is going to be a long-term process. You know it may have a placebo in it: I won't know whether you're getting the real drug. You won't know whether you're getting real drug. So I explained to them that you know, when we're in these kinds of trials, part of the most important part of the trial is being able to, at the end of the trial, still be involved with the trial, because they have to have a certain number of people finish the trial to get realistic information yeah.
Dr. Doug Denham:
9:09
And that's what our job is, ultimately. Ultimately, that's what their job is as the participant in the trial with us. So so we're. So we start out that way and you know I ask them to be honest with me. Do you think you can do that? Even if you don't, you know if it turns out you're not experiencing weight loss, you know you're still going to be getting a lot of benefits. You're going to see in me or my, you know, or somebody in our staff on a, you know, fairly regular basis looking at your health.
Dr. Doug Denham:
9:37
We're going to be doing, you know, lab work to see how things are going. Also, part of these trials generally, there's some dietary and lifestyle training that you're doing with them. So I encourage them that. You know these are all. These are all important parts of of maintaining your weight throughout the trial and and at the end of the trial. Because you know, at the end of the trial, whether you were on it or not, we're going to take it away from you and you're going to be stuck out there.
Dr. Doug Denham:
10:03
And if you haven't learned something during the trial about how to eat better and exercise and do those lifestyle modifications, you're going to go right back to where you started and you know you're right where you started. So we try to get them in there and try to sort through them that way. Our staff is really good our coordinators and folks like that. They're also very good about keeping in contact with them and encouraging them. Most of the time, the sponsors will have some strategies that they'll you know they have as part of the trial, where they're periodically giving them water bottles and that kind of stuff. It's just incentives.
Dr. Michael Koren:
10:40
Chachkis, I think, is the technical term for that.
Dr. Doug Denham:
10:44
Yeah, so you know, but, and some patients really enjoy those things. But I think the like I say, and then at each visit we're, you know, while we're talking, we deal with some of those issues. You know, I tell folks, particularly in a weight loss trial, I said you know, everybody responds differently to the medication. So you may be one of those non-responders or slow responders and it's just going to take a time. When you look at some of the, you know, at some of the early trials with these things, I mean it took for, like semaglutide, it took some of these people to really start losing appreciable weight 24, 26 weeks out into the study. So you know it's kind of hard to you know if you're not dropping 10 pounds in the first week, that's not something to be worried about.
Dr. Michael Koren:
11:26
Right, and semaglutide is ozempic for those people not familiar with it.
Dr. Doug Denham:
11:31
So, yeah, so it's k ind of an ongoing process. Yeah, Inevitably you may you do reach that point where they're really kind of like you know I'm not, you know I'm not seeing what we, you know what I want to see, and I think exploring kind of you know again what, what were your expectations? What goals did you have? Maybe that you know we didn't talk about before, that I wasn't aware of, about the amount of weight you're going to have. Was it realistic to begin with? And then we'll talk a little bit more about. You know, like I said, you know the altruistic aspect of doing studies is, you know you may not get benefit out of this trial, but if you're here helping us find the answers to these questions, you're doing something. You're giving back to the community and to the world.
Dr. Michael Koren:
12:16
Yeah, that's a great point. Yeah, that's a great point.
Dr. Doug Denham:
12:18
And so you know, try to encourage them that way. Some, you know there are those individuals who just kind of, once you know, once they lock themselves down and not you know they're not going to do that. Then I think the other alternative that you know I will explore with them is okay, you're two years into the study, We've got another year to go. You're tired of coming in and doing all those things. You're tired of doing, taking medicine that you don't think is helpful for you. Let's do this. Will you stay in the trial just as a participant? We'll still have you come in for visits to draw blood and things like that. You'll still get your stipend for doing those things. If you are willing to do that? If you're not willing to do that at all please show up on the last day that would have been your last day of the trial just for the end of study medication or your checkups and things like that, just so we can close out the trial and that helps the sponsor in terms of their number of people that participated and completed the trial.
Dr. Michael Koren:
13:23
And the science, of course. Yeah, helps the science, yes.
Dr. Doug Denham:
13:26
Yeah, and I think so. So it's an in-depth, it's a challenge sometimes, but you know, it is amazing to me how many people just kind of, I think, in addition to the trial they're getting that social contact with our staff and our facility. The people, you know I laugh sometimes, I think the girls out front at the front desk, receptionists. They know the patients better than I do because they spend more time talking to them and you know they know about their families and grandbabies and all these other crazy things. Sometimes it's interesting that way. But so I think there are other benefits that we try to explore too with them, about participating, continuing to participate.
Dr. Michael Koren:
14:07
So you hit on such an important thing, which is the engagement piece, is that a lot of our patients find tremendous value in the engagement. They don't get that during traditional medical interactions anymore and they love that. And a good investigator and a good coordinator will figure out what drives the patient to come in, whether or not it's just chit-chat about what's going on in their life or little tidbits about what you learned at the latest conference. People seem to love that. Or you're looking at their whole health record so you may say, hey, did you look to see what's going on with this particular problem? I noticed that while you're here you're a little short of breath. Have you had that checked out?
Dr. Michael Koren:
14:51
Or we did an EKG as part of this and it's nothing major, but there's a little something here that maybe requires a little bit of attention. I can help you follow through on that. Or just lifestyle stuff. So I'm a big fish eater, for example, and I like to tout all the benefits of fish. So people love that kind of engagement and I'm a big fan of halibut.
Dr. Doug Denham:
15:19
I've had halibut, yeah, but I wouldn't say it's my choice.
Dr. Michael Koren:
15:21
Okay, well, I'm going to have to prepare you my special mustard-based halibut. You're going to love it.
Dr. Doug Denham:
15:26
That sounds very good, all right.
Dr. Michael Koren:
15:28
But these are things that patients really enjoy. They like that interaction and certainly I think a lot of our patients would benefit from getting some of the processed foods out of their diet and more healthy foods and foods that, quite frankly, will help them lose weight if they're just a little bit more careful about what they put in their mouths.
Dr. Doug Denham:
15:46
Right.
Dr. Michael Koren:
15:47
So that interaction goes a long, long way. And then the other thing that you kind of alluded to, which is super interesting, is that you got to keep them in, especially for that primary endpoint, which may be how they're doing at year one, two or three, and be mindful of that as an investigator and make sure the patients understand that the scientific validity of the study requires them to be there for that visit. So even if they choose not to take the investigational product, it's still important that they kind of do their thing and come in, and especially for those key endpoint visits.
Dr. Doug Denham:
16:26
Right, yeah, yeah, it is. You hate the patient that just disappears into the sunset. You never hear no word from them and suddenly they stop answering the phone calls and not answering. Yeah, that's a real problem, yeah.
Dr. Michael Koren:
16:39
So we certainly try to do that, and then I know your experience with this. But from a sponsor perspective, we encourage the sponsors to provide open-label treatment for a lot of these patients after they complete the blinded part of the study. It's a huge driver for people to be compliant with the protocols and ultimately to have a positive perception of the clinical research process. Have you had a success with that in the past?
Dr. Doug Denham:
17:08
Yeah, I think, yeah, you're right and I will even ask that question sometimes, you know, as a study starting when we're talking with them about that is, you know, is there, you know, are we going to have a chance where the patient will be unblinded and actually be on product for, you know, a certain period of time so they can get that benefit from it? So you know, I think those studies probably are easier to keep people in than not, you know, but some of the sponsors are receptive to that, unfortunately too.
Dr. Michael Koren:
17:38
So yeah, absolutely. Well, let's take a quick break and then I want to delve into cardiovascular outcome studies with you. As a cardiologist, I do lots of those. I know you've done plenty of them during the course of your career and they also present some challenges in terms of retention, and we'll dig into that in just a moment.
Announcer:
17:57
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