Good Clinical Practice is a Good Patient Experience

Transcript generated by AI.

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.

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To continue watching this podcast episode, head over to MedEvidencecom

Transcript generated by AI.

Announcement: 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! I'm having this fascinating conversation with my colleague, Doug Denham from San Antonio, Texas, and we were talking about what life is like as a clinical trialist. Both he and I spend most of our professional time conducting clinical research, and we were also talking about the challenges of keeping people in studies. We call this the retention strategy how people stay in studies, and it is so important from a scientific standpoint to make sure that people stay in the study through the primary endpoint, because that's ultimately the science of the study, and without hitting that primary endpoint, the effort of the patient goes to naught because we're not able to make any kind of legitimate, structured scientific observation. So Doug and I had this discussion in a particular area that's sometimes very challenging to keep people into studies, which is obesity, and the simple reason for that is if you're in an obesity study, you want to lose weight, and if you're in the study and you're two, three, four months in a study and you're not losing weight, you're going to get frustrated.

Dr. Michael Koren: 1:24

And some of these studies may be long-term studies one, two or even three years out. So Doug had some nice suggestions about engagement and how important that is. But, Doug, I'm going to throw something else out. So we talked about all the things we do to get the patients motivated, but I think it's only fair to talk about what we need to do to keep the sites motivated. So share with the audience your experience about sites or places that get a bad reputation because they're unable to keep people in studies such as obesity studies.

Dr. Doug Denham: 1:54

Yeah, you're right, it's very important that the staff is aware and understands the purpose of the trial and the importance of maintaining retention of the patients. So that's something that we talk amongst ourselves, you know, between visits with patients and things too. And I mentioned earlier that you know my coordinators are really good about establishing relationships with the patients and so you know they're the first ones to know generally if something's not going the way they want to do and we'll talk about that. So one I'm aware of it when I go into the room to see the patient and so we can start talking about issues that way. But I think, like you said, it's important that the staff know that this is a key part of it, and I think they're a key part of how that happens, by their involvement and just and and and just interaction with the patients. I guess you were talking earlier about how they you know they get to know the patients.

Dr. Doug Denham: 2:52

They know you know grandchildren, they know husbands they know, you know I'm going on a trip to you know I have, I have a number of patients. We're close to the border here, Mexican border, and there's there's quite a few casinos down that way. And so we have quite a few patients that are, you know, they make regular trips down there and so they're always, and a couple of our staff, like, make regular trips down there too, so they compare notes and things like that. But again, it's that building a relationship.

Dr. Michael Koren: 3:23

And when they lose money they have to come back to work. So that's a good thing, right, yeah?

Dr. Doug Denham: 3:26

Yeah, yeah, I gave a patient who really her husband was telling me she was killing him because she was making so much money it was affecting them. They were both on Social Security. Oh, boy, and he was killing him, and so I gave her a dollar one day and said you know, win some money for me. So when she came back in I said, how'd I do? She said you didn't do so well, so I didn't give her any more dollars.

Dr. Michael Koren: 3:50

All right, that was smart.

Dr. Doug Denham: 3:52

That was just part of our relationship and it was fun, we talked about that and so I think it's important

Dr. Michael Koren: 3:57

Yeah, yeah that human engagement is so important about keeping people in studies

Dr. Michael Koren: 4:06

Just to flesh out a little bit, this concept of the reverse is sponsors keep track of data on how well we retain patients.

Dr. Michael Koren: 4:11

So, if your site develops the reputation of having large dropout rates, they're not going to like that and you're going to have a real hard time getting another study. Now I think sponsors are going to be more forgiving, if patients are in studies, they don't tolerate the IP, the investigational product, but they stay in the study and we continue to monitor them. So that's fair game. But if you have people that just get lost to follow-up, ultimately that reflects badly on the site, on the principal investigator, and makes it difficult for you to get other work with that sponsor. And then ultimately you want to flip the script and say, hey, even in these difficult studies such as obesity studies, which typically have very high demand in our populations, we're able to pick the right people that stick with the program.

Dr. Michael Koren: 5:00

And if you get that reputation then you'll be very competitive in this space where lots of sites want to participate.

Dr. Doug Denham: 5:07

Exactly yes, yeah, we're very aware. We discuss at our administrative meetings every week. We discuss retentions and issues that are coming up with that, so some of the studies are more difficult to do that in. But, like you say, you got to do your best because at the end of the day, you want them to come back for repeat business with you.

Dr. Michael Koren: 5:26

Yes, it is important, and you made the very important point during our previous session that giving people a good expectation of what's going to happen in the clinical trial is so important. So, again, you may or may not lose weight during the course of this program, but you'll have me, you'll have my staff, we're going to check your labs, we're going to do these other tests, we're going to give you the results of the other tests. I'm going to give you information that you'll be able to use for the rest of your life to maintain your weight, because, even though you may need some medicine to help you lose weight initially at some point, we want you to be able to maintain that on your own, and without these learnings, it's going to be very difficult for you to do that. So please take advantage of that opportunity and by stating it that way, hopefully you have more success in keeping people in.

Dr. Doug Denham: 6:15

Yeah, yeah, it's key. You got to see what they, yeah, what are they expecting to get out of this for themselves? Absolutely, they're not always in it for humanity.

Dr. Michael Koren: 6:24

You you got it, you got

Dr. Michael Koren: 6:26

So let's transition now to cardiovascular outcome programs. So we've both been in plenty of these programs and they could be situations where we're treating a cholesterol problem and want to see who's having fewer heart attacks or more strokes of the course of period of time, comparing-treated patients with a placebo or an active control. That would be a typical study. Or it could be in congestive heart failure, people who can be really, really sick and we want to try an intervention to keep them out of the hospital. Again, this is a clinical outcome that we're trying to prevent happening through the study intervention, and these folks can be tricky. They can be tricky. So, for example, if it's something that's measurable, like your cholesterol level or your lipoprotein( a), what stops the patient from getting a measurement outside of the study and kind of figuring out if they're on the active drug or on a placebo or a comparator that may not be as powerful? What's been your experience and how do you handle these things?

Dr. Doug Denham: 7:30

Well, we actually. It's interesting you bring that up because we actually had a patient not too long ago whose primary care doctor decided, you know, they wanted to be on top of things and doing the right stuff. So they drew Lp(a) and shared that value with them.

Dr. Doug Denham: 7:44

And so they came back in saying you know well, my Lp(a) hasn't moved at all since we started this trial, because I'm blind to it. They're not letting me see that data and I'm kind of like, okay, why did you do that? It's one of those things that, we have to remove you from the trial now because you're unblinded, basically. So again we try to set them up for success early on by telling them "you can't do this." If your doctor wants to go through that then you need to tell him 1. you're on a trial

Dr. Michael Koren: 8:37

So as an aside, just as an aside for our audience Lp(a) stands for lipoprotein( a). It's a type of quote cholesterol molecule, actually a combination of fat, cholesterol and protein that's associated with bad cardiovascular outcomes, and about 15 to 20% of all people in the US have this problem. It tends to run in families. It's a genetic condition, and both your site in San Antonio and our sites here in Northeast Florida are running studies in this area as we speak. So if you hear this podcast and you're interested, give us a buzz and we'll get you involved in some pretty cool cutting edge research.

Dr. Michael Koren: 9:14

Sorry for that commercial inside the podcast, but I couldn't help myself. But getting back to the retention question, so what strategies have worked for you? To one prevent people from cheating.

Dr. Michael Koren: 9:30

It's kind of a form of cheating because they should know that they're not supposed to look at these things. In the case of Lp(a), we don't have any standard therapies that can treat it so quite frankly, there's not a huge value for them to get that level outside the study. But you make an important point that if they tell you about it, then all of a sudden you are unblinded and now you're not objective in terms of your assessments. You're now could be accused of having a bias and that creates all kinds of problems for the study. But go ahead, right?

Dr. Doug Denham: 10:00

So yeah, you know. And so yeah, it's important to let the patients, you know, educate them about kind of the do's and don'ts of the trial while they're on it. That way, you know, I'm a big advocate of patients telling their primary care doctors or their cardiologists, you know, whoever's managing their care that they're participating in a trial, because I think it's important they know that and you know, and that may make them more aware of what they can and can't do if they've done trials before too. But it also allows us again to to educate the physician. A lot of times you get a letter that the sponsor has generated that you can send to their primary care doctor letting them know what the patient's in this study and that kind of stuff. So you can kind of let them know that. You know, please don't do this, please don't do that.

Dr. Doug Denham: 10:58

You know, we're always asking them.

Dr. Michael Koren: 10:59

And please don't tell us.

Dr. Doug Denham: 11:00

Yeah, exactly, yeah, well, yeah.

Dr. Michael Koren: 11:02

You know again, we don't want any of them to be getting study information or study relevant information outside the study. But if it happens to happen, we don't need to know about it so that we can maintain our blind, and that's important.

Dr. Doug Denham: 11:16

Yeah, and then you know you're obviously asking them about. You know, every time they come in, about any new medications that have been added and things like that that could also cause problems with the study in terms of data and things like that. They are hard. And then, on top of that, you know you're looking at a process that, because a lot of these studies require them to have some kind of cardiovascular history, and so you're trying to monitor that in relation to are we doing something that's making that worse? Or you know those kinds of things or them being making you aware of it.

Dr. Doug Denham: 11:55

I mean the other thing that I'm sure you've run into this too, but you know you'll get a call from the patient and they've been you and they've been in the hospital. They had a heart attack or they had a bypass or all this other stuff, and it's like, why didn't you tell us this sooner kind of thing. So now we're behind on our paperwork, letting everybody in the study know what's going on.

Dr. Michael Koren: 12:15

and just for the audience using the GCP language or good clinical practices language, that would be considered an SAE. Serious Adverse Events? Absolutely, and we have a responsibility for reporting that actually immediately upon learning. In a practical sense, we're expected to get that information to the sponsor within 24 hours. The actual federal law states that that should be reported immediately. But that's part of our job as principal investigators. But go ahead, sorry to interrupt.

Dr. Doug Denham: 12:47

Oh no. And so that starts a whole cascade of effort and challenge to get the information from the hospital, get it to the sponsors and then answering their questions about that. And one of the things that drives me crazy about SAEs is the people on the sponsor side of it may not have any idea what actually happens in a hospital environment, or anything like that. And they're asking questions about things like, who cares what Tylenol doses they got? I had nothing to do with it Right Right.

Dr. Doug Denham: 13:21

Right, right. Yeah, they dwell on these things. It's like that's not really the important part, you know. Let's talk about this.

Dr. Michael Koren: 13:26

Right, exactly that's right yeah.

Dr. Doug Denham: 13:30

And then when getting them back in so that we can do things that may need to be done on them per protocol of the trial. You know, there may be special tests that they want us to run, those kinds of things. One of the challenges of doing these kinds of trials is keeping up with them and then making sure you're making everybody who needs to be aware of changes and that aware of it for them to do their analysis and their safety committees and those kinds of things.

Dr. Michael Koren: 13:59

Yeah, yeah, you bring up a great point, which is that communicating with the patient about how important they are to me is a really good strategy for retention.

Dr. Michael Koren: 14:09

So, they're important because if they end up in the hospital, they have some adverse reaction. Lots of people want to know about it. People want to know every detail and, quite frankly, in clinical practice we poo-poo a lot of things because we just want to go about our business, but in clinical research, we dwell on these things and people tend to like that. They like the attention and they feel important and it's a way to give back also, which is a very important element to explain to patients about the altruism. That your experience is going to be shared with doctors and people all around the world, and so you're actually part of this incredible knowledge generation and knowledge sharing that really moves medicine forward, and I think that makes people feel good about their participation.

Dr. Michael Koren: 14:54

And then, finally, what very few people know including, quite frankly, a lot of physicians is that the statistical analysis plans of a lot of these studies require you to consider anybody who drops out that has lost a follow-up as somebody that's had an event or somebody who didn't survive to follow up as somebody that's had an event or somebody who didn't survive. And so, even if 1% of the patients get completely lost to follow up and they're all considered dead, well, that could torpedo a product that's otherwise really, really helpful and beneficial to people, because you have to make this assumption. So knowing the vital status whether or not people are dead or alive is really important. Keeping them in the study even if they don't tolerate the medication is really important, and constantly telling the patient that it's not only about your experience, of course, that's really, really important, but consider everybody else. So again, if this 1% of people don't follow the rules of the study, then the other 99% of people who are in the study may not get value to their visits.

Dr. Michael Koren: 15:57

When you think about it that way, typically we can bring people along to at least make sure we know if they're dead or alive and make sure that they keep touch with us, even if they're not taking the investigational product.

Dr. Doug Denham: 16:10

Great.

Dr. Michael Koren: 16:17

Great yeah. So those are really, really important elements of engagement and making sure that we do a good job in retaining patients, and we talked about it during the last part of the program that allowing people to get open label access to an investigational product is a really good strategy. We've done that in many, many studies and kudos to the sponsors that provide that. It makes a huge difference. The patients perceive that incredibly well and it's a very effective strategy for keeping people engaged and involved in the study, even if people have a suspicion that they're not on active medicine. So we thank you, sponsors for that.

Dr. Doug Denham: 16:51

Definitely

Dr. Michael Koren: 16:53

Doug any closing words for the audience in terms of retention and things that we can do to make sure people have a positive, safe but ultimately a scientifically valid experience in studies.

Dr. Doug Denham: 17:08

As we've talked.

Dr. Doug Denham: 17:09

I think, just engaging with the patient from the very beginning, educating them about you know what the process is going to be, because all these folks don't, they don't understand, they're not scientists and they don't understand what's going to happen, and so they have a good feel for what's going to happen.

Dr. Doug Denham: 17:24

And and then just being available to answer their questions. It may not be me answering the question, but it's one of my staff members that it's capable of providing the information that they need and just being being there. You know, one of the things I usually, with the last words out of my mouth, is I'm, as I'm ending an appointment or a meeting with the patient, is, you know, if there's any issues or concerns or problems, you pick up the phone and call us, We will get right back to you. If we don't, if we don't pick up the phone, you know, cause your safety is the most important thing to us and we appreciate that. But I think just making them aware that you know they're they're important, they're the most important part of the, of the of the process, quite honestly.

Dr. Doug Denham: 18:04

And so without them, yeah, you know, we can't do what we do.

Dr. Michael Koren: 18:09

So we're all replaceable, except for the patients, right?

Dr. Doug Denham: 18:12

Exactly

Dr. Michael Koren: 18:14

Yeah, and I'm going to emphasize that. The point that you just made, which I love, which is the one place where I think we can do a little bit better, is to let patients know about the results of studies and have them come in and show the publications and say if it wasn't for you, we wouldn't have this.

Dr. Doug Denham: 18:34

Right.

Dr. Michael Koren: 18:35

And that makes it very tangible for people to say, oh my. God, I was subject to this analysis and this is now a scientific paper that people all around the world are looking at. And isn't that cool. Isn't that creating value for me? And isn't this making me feel good about the time I spent at the Clinical Research Center? So I'd love to see more communication, the study results of the patients.

Dr. Doug Denham: 18:59

You know it's interesting that you're bringing it up. I think here recently we've had more of that kind of feedback with the sponsor, with a paper, a summary of the results that's written more in a layman's term to hand to the patients or send out to them so they understand it was worth my time and effort. So I agree with you, the more we do that, I think one of the areas probably where the industry could do better is publishing results of the studies that maybe didn't do as well, but at least letting us see what was the problem and being able to share that with the patient, Because sometimes people ask, well, what happened? And it's like, well, I don't know. They stopped the study and it's been silence and crickets since then.

Dr. Michael Koren: 19:46

Right? Yeah, that's a great point. It's a great point. And in many cases, studies are stopped not because there was some huge problem, but the effect size wasn't as much as they had anticipated, or they have a competitive product or a number of other things come out that change their whole strategy in terms of what products they want to develop. But that doesn't mean that there wasn't some good that came from their study participation, and we can certainly highlight that to our patients if we're providing those data.

Dr. Doug Denham: 20:16

Yeah, because they want to see what did I help you do, Exactly?

Dr. Michael Koren: 20:24

I think that's so important. Saying thanks is one of the most important things we do for other human beings, and I've seen a few sponsors actually thank the volunteers when they're doing their promotional ads. So I love marketing ads that actually thank the volunteers who are involved in getting the science out and getting the drugs approved. So I love that. So keep up that good work, sponsors. We appreciate that. Our patients appreciate that. Doug, this was a delightful conversation. Thanks for joining me, thanks for being part of the MedEvidence! family, and we definitely have to do it again on another topic.

Dr. Doug Denham: 20:58

Sounds great. I've enjoyed this and look forward to the next one.

Dr. Michael Koren: 21:00

Okay, here's to retention.

Dr. Doug Denham: 21:02

Yes.

Announcement: 21:04

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