Dr. Maddux: Including clinical and patient-reported outcomes, or PROs, in the CONVINCE clinical trial opens new and meaningful pathways to understand medical care from the patient's point of view. By combining clinical and patient-reported endpoints, we can identify opportunities to improve patient health status and define treatment goals. Dr. Professor Matthias Rose is a contributing member of the CONVINCE Research Consortium and his research is concentrated on putting the focus of medicine back on the patient. Welcome Matthias.
Dr. Rose: Thank you. I'm happy to be here.
Dr. Maddux: Let's start by having you briefly explain how did the CONVINCE study actually incorporate patient reported outcomes and your perspective on why that was important.
Dr. Rose: I was very happy that the Convince Consortium, you know, which was driven by one of the probably the most influential nephrologists in the field. They decided right early on to look for somebody like me or others in the field to, to give this kind of patient perspective. And I think the basic idea was to move one step further from already, a very sophisticated care model, which means biomedical care model, to evaluate what is the effect on the patients from their own view. And to do that, I think just the thought to do it was maybe even the revolutionary way to do it. And then they were just looking to somebody who's able to do the techniques. And that was me and I was happy to be included and it was a great time to work with them.
Dr. Maddux: Tell us a little bit about what the themes were that were documented in patient reported outcomes in the study and maybe give us just a little background on some of those details.
Dr. Rose: It's not entirely a new field. And then I was working in Boston also for quite a while. And my mentors, John Ware, he started this study together. Then also was Ron Hayes and many of those of the people in the audience know this because he's one of the developer of the KDQQL, John Ware of the SF36. So the field started many, many years ago. So over 30 years. So we are looking at the body of evidence how to do it. So the techniques of we call this psychometrics. But what now is going to change that the clinical field in particular the people who are taking care of chronicle patients are understanding that might be even as solid science as you do or you used to do with laboratory findings. So by doing that, we were of course, you know, first not just thinking if there's an instrument out, which is established, we are doing this in the consortium a little bit differently. So we were looking for the groups who were, you know, conceptually thinking of what is the core outcomes. And so one of the most prominent groups there among others is the Song initiatives and the Song initiative, the tremendous work over the last years to define, they call this tier one, tier two, tier three outcomes of what they consider core importance. And so one of those core constructs is the tier one outcome, obviously is fatigue because clinically, you know, from the physician's views, but also from the patient experience, fatigue is one of the important aspects you experience as a patient. And then we went a little bit further and to evaluate what is generally recommended, not just for patients with end-stage renal diseases because often they have other chronic conditions like diabetes or some of them have heart failure. So we were opening our view a little bit broader and say, well, what is considered healthy and this is certainly not just fatigue. So we had a core aspect and we put a lot of effort also to find the best possible instruments, but also maybe expand our view on the fatigue. But then we also want to be comprehensive and included other domains like physical functioning, cognitive functioning, depression, social participation.
Dr. Maddux: One of the other features, as I recall, was the electronic capture of this information by patients, which we still have many, many patient surveys and various instruments that are still paper form or not electronic. Describe how easy or hard that was to execute.
Dr. Rose: I think that there are two aspects to your question. One is that, you know, we are used to an instrument driven assessment system so that you have a sometimes very bulky, you know, long instruments, so either paper or electronic. And then the other thing is that, of course, the mode of administration is important, how, smoothly it would fit into clinical practice. And that was another thing which is very close to my heart or the group, which I'm sharing here at the Charite is that we need to have so-called patient reported outcomes or patient health status measures. They need to fit into clinical practice because otherwise we will not be able to get the knowledge we need from real world evidence. So to answer your question in two folds is we were looking for a measurement system from the content wise, which is the modular system, which is not just one instrument. So we can measure domains and then this gives us the flexibility and we are building on an auto measurement system, which was generously supported by all the NIH in the state with the PROMIS measurement system. Why is this important? Because this gives some flexibility to tailor the instrument to the individual. So you can have a certain instance a longer means. a little bit more board in some instruments where you need precision. And in some instances, you need to have smaller instruments, but you're still measuring on the same metric, which is important to answer your question from the method side, from the technical side. It is equally important than in certain environments, like more or less the Western environments, you know, the technique needs to fit into the workflow. And so we program for this case, a particular software system ourselves. based on our previous work, to be as smooth as possible. And I'm very happy to say that the three went well. And for other environments, we have over 60 participating centers. They said, well, they are more comfortable with paper assessments. So they had the chance to choose one or the other, although we preferred the electronic devices. But it was a specifically programmed system.
Dr. Maddux: As we think about the patient-reported outcomes, looking at symptoms and quality of life and a variety of measures, we know today the outcome from the primary endpoint of all-cause mortality. What do you think the impact of a positive set of patient reported outcome results would have in the decision making on what patients are good candidates for HDF? I'm just curious what you think the impact of the patient reported outcomes will be in addition to what we've already heard from the other if the results are positive.
Dr. Rose: What I observed on both sides of the Atlantic is that patients are more and more want to be involved in those kinds of decision-making, and that the focus... in particular in a situation like we have in dialysis, is clearly mortality. And we have seen a positive result here for one intervention in our trial, but it's still, you have a limited time with both interventions here. So the quality means the ability in the rest of your life to participate in life. And this is obviously determined also by the number of... symptoms you experience by your level of physical functioning or your cognitive functioning, I think will be from the patient perspective one key interest. And maybe it seems a little bit difficult when because we are both, you know, doctors and we are used to think of improving biomedical markers. But when you think from the patient perspective, it might even be a little bit provocative, independent how long you live, it's always your entire life. You know, it's always the entire life. It might be a year, it might be two, it might be 10 hopefully, but it's always the entire life. So from the patient perspective, it might be even more important how your life might be instead of how long your life might be. And I hope that you don't consider this provocative, but it's just when you make this change in perspective from us being physicians to them being patients, and sometimes we will also be patients.
Dr. Maddux: In my experience our value-based care evolution for the company in kidney disease has also changed that lens from being the successful completion of a treatment to this broader view of how does somebody live their life with this advanced disease. And so I do agree with you completely that this concept of how are you living your life with advanced kidney disease becomes the more important predicate than simply the duration of that life. I think that will be. I'm curious whether you think the way that you have included patient-reported outcomes into the formative endpoints, secondary endpoints of the clinical study, do you think you've set a precedent in which all major clinical trials in kidney disease need to include these elements?
Dr. Rose: Well, I don't know that obviously needs to be judged maybe 10 years later if this was successful or not, but we did the best to be in one way as comprehensive as possible and in the other way having a focus to choose the tools which will be applicable in one way or the other in clinical practice. So my hope is that we will have shown with this trial that a very comprehensive assessment that we are talking about over three years, about 10,000 questionnaires, which we have been able to collect here. So I think we can give the most comprehensive picture about the trajectory, independent which kind of treatments you have when you're in dialysis. And we also have shown that it's feasible to do it in Romania equally, like in Spain or in Germany. So I think this is probably in the long term or the midterm even, it will be equally interesting to say, okay, is this possible? And this was not the study nurse, which was next to the patient's bed. So we included that in clinical routines. And so I hope that this will be useful information for further trials, but also maybe for clinical practice that we can treat PROs as a laboratory parameter which we are used to measure very often to get us informed.
Dr. Maddux: For the clinical benefits of HDF in Europe, I think there are many opportunities to take the data that's already out there from the CONVINCE study and utilize that as a way to make sure people are offered this option more readily. In the United States, there is effectively no HDF occurring today, but the opportunity for that to begin to occur in the future, I think, is quite real. The patient-reported outcomes will be a big piece of that story. Can you give us any insight into both the timing and the methods of when you anticipate being able to speak to that part of the CONVINCE study?
Dr. Rose: I wish I could disclose this right now because I'm sitting right in front of me of the paper, which is about to be finished. So, but as you know, within the consortium, we agree to not to disclose any kind of data until the publication is ready. but it will be in the new in the new future. I hope to talk about this.
Dr. Maddux: I know that everybody will be anxious to see both what the outcome was, but the thinking of the consortium and how the interpretation is of these data.
Dr. Rose: Your audience might be people who are very experienced in patient reported outcomes and others might not be. And, you know, the way I usually try to describe this is not we are not talking about an unusual thing for medicine. So we used maybe hundreds or even thousand years that we asked the patients, how are you? This is not a rocket science. There's nothing new. So we asked the patients, how are you? And, and the only thing which we do now is to make this kind of knowledge, an aggregated knowledge, is that we put this, how are you, in a number. So it's nothing unusual or something which is kind of, strange to medicine. It's just, for me, the most natural thing that we include this in our research findings, but also in our clinical practice, like we do on an everyday patient. The benefit to do it scientifically means to put this into a number using solid method is that we can share this information in a trial like this. So we can share the information, we find best practices, as you just mentioned, you know, in the US or in Europe or in other places in the world, that we can, you know, look who is doing what we started to do, because to make the patient feel better, and in particular in dialysis, it is, you know, the natural understanding. You have a chronic condition, you take care of the patients and you want to know if this taking care is successful or not. So it's nothing unusual, we just make it happening and it's not rocket science, we have smartphones, so it's easy to do.
Dr. Maddux: One of the things in nephrology and other areas of healthcare, but certainly in our field, is we have not been terribly quick to embrace qualitative research as opposed to pure quantitative laboratory-driven type research. Do you feel there are other things that could catalyze our understanding of the methods and the ways of looking at qualitative data in addition to patient-reported outcomes that we can create quantifiable endpoints on. There is probably quite a bit of information buried in just what people say, what they talk about, and some of the other more qualitative features of asking these questions.
Dr. Rose: I think that's a wonderful question for me. So it's because, you know, the field was a little bit started even as the quality of life. So we assessing quality of life. So that's probably sparks your question. Say what was the qualitative part because you describe your quality. In fact, what you do, although it's subjective because you ask me how I feel, you know, how I perceive my ability to social participation. So it is in qualitative description. But in fact, we transfer this qualitative feeling into a quantitative thing, which is, you know, making a number out of it. So it is this shift, which I think needs a little bit of, you know, understanding and maybe also a little bit of education to say, well, can we really feel that those data are as solid as you would, you know, assess potassium level or QRT mean, and I think personally I was very skeptical. I started my doctoral thesis with PROs and I said, well, the question here, what this is, I started with intensive care and then somebody came around to the questionnaire. But now after many years doing this research and very confirmative results, I'm trusting that we see when we know the methods, we need to find way to interpret the methods, but it's not that it is an open level field anymore. So we do know what we are doing. I think when it comes to the core health outcomes, like as I just said, fatigue, depression, physical functioning, social participation, I think we do have an agreement that I think we can say, although it seems qualitative in the fact that there's a number which is, can be solidly treated as signs.
Dr. Maddux: Have you and your department at Charité spent much time at this point thinking about the potential of the future to use large language models and generative AI as a way to elucidate information from patients? And I'm curious what you think the future might hold for that.
Dr. Rose: This is a hot topic and I'm always in danger to be a little bit too visionary, if you would ask my colleagues. But I agree with you that, you know, with natural language processing and all the things which are, being there. I think we... As always in science, we are thinking what will be the next question tomorrow and how we can answer the question. And I think now we enter something in Google, some search terms, but I think we are more and more used to use our microphone and say this. And so I think the validity or maybe the intuitively of a patient to, as I just said, we are mimicking a little bit, very clinicalistic the communication we’ve had for a thousand years, so as a patient, as a doctor, asking how do you feel. So I can envision, I don’t know if I will be a part of, but the point is very fast, that we capture this communication between doctor and patient out and put it on the metrics which we just introduced with CONVINCE which was already from a psychometric point of view, pretty innovative, because we moved away from an instrument to a construct-driven system, which is the prerequisite for what you just been asking. So we have to agree on Celsius or Fahrenheit before we can argue which is the instrument to measure this. So we have to first agree on the scales. I think we have many people and now we can think of the methods and to do better things in the future than we can do now. So I agree with you. That is the way to go. But first, I'm very happy if many people are using PROS in clinical practice the way we can do it already.
Dr. Maddux: Before we finish, any final thoughts about what we can anticipate and what you feel you've learned from incorporating these into the CONVINCE trial and what might we expect next from the consortium?
Dr. Rose: Maybe two questions and that's really close as where we started. I think the major shift is always if you shift your attitude or you shift your perspective and then it follows what you do. So it's the action follows your way of looking at things. And, and I think the consortium, the reason I was so happy was that they first started to shift the perspective. I would say from a disease perspective to a patient perspective, this is not like you, leave one. to in exchange to the other. It's complimentary. So you have the disease perspective, which is of course kidney failure, but you acknowledge there's a huge variance of this in the patients, you know, how they perceive this. And this opens totally new opportunities also for companies like Fresenius or others or the pharmaceutical industry. Once you embrace... this understanding that it's about patient care, it opens a totally new set of tools. Because once you identify the group who's, despite you're doing the best biomedically, not happy or doesn't achieve what you think it achieves, you can use other tools like you know, maybe the social support, maybe how the nurse is treating the patients. So once you acknowledge that part and you have data, because I think we should be science driven, data driven, to see that might be a psychosocial intervention or might be the atmosphere in a certain center. And I don't essentially mean that we have to benchmark this that one center is better than the other, but if you have a center and certainly you have a drop in the perceived health of your population, then you can go there and say, what is going on? Is there something which you would like to acknowledge? And so this information I think is so natural and so easy. around there and I think that's the reason I'm very happy that the consortium made those kind of attitude shifts and I'm very happy that Fresenius and the other companies were courageous enough to say well we do it we look at this because it's not without risks for doing this and so I'm very happy to be part of this consortium which is I think a perfect example for a public-private partnership.
Dr. Maddux: I'm here today with Professor Matthias Rose from Charité, who was central to the development of patient-reported outcomes in the CONVINCE trial. Matthias, thanks so much for joining us today on Dialogues.
Dr. Rose: Thanks for having me.