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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