Assessing Patient-Reported Treatment Values in COPD

Chronic obstructive pulmonary disease (COPD) accounts for substantial societal and economic burdens in the United States. Despite numerous pharmacological and disease management advancements in recent years, studies continue to explore how COPD affects those who suffer from it both physically, mentally, and economically.

In one of their recent investigations, Robert Reed, MD, professor of Medicine and associate medical director of the Lung Transplant Program at the University of Maryland School of Medicine, and Julia Slejko, PhD, assistant professor of pharmaceutical health services research and research core lead at the Patient-Driven Values in Healthcare Evaluation (PAVE) Center at the University of Maryland, among others set out to establish a prioritized set of patient-informed value elements based on the lived experiences of those with COPD.

By highlighting which aspects of COPD treatment patients rank as most important, the study provides a foundation of measured values that can better direct future clinical trials and research into COPD disease management.

In an interview with The American Journal of Managed Care^® (AJMC^®), Reed and Slejko explain how they carried out this study, next steps in this area of research, and potential lessons learned from the COVID-19 pandemic.

The following interview has been edited for length and clarity.

AJMC^®: In one of your latest studies, you both sought to establish a prioritized set of patient-informed value elements elicited from individuals with COPD. Can you describe the impetus behind this investigation and explain how it was carried out?

Slejko: We established the PAVE Center at the School of Pharmacy a few years ago, which was funded by a Center of Excellence grant from the PhRMA Foundation in value assessment. One of the main goals of the center was to really start to lead some establishment of methods for patient-driven value assessment. In brainstorming how we were going to do that and thinking about expertise that we had within the center, another colleague of mine, Susan dosReis, BSPharm, PhD, who is the director of the Center, had a lot of experience in patient preferences and eliciting stated preferences among patients. Thinking about how to bring that into value assessment was really the inspiration for the way that we wanted to conduct patient-driven value assessment by focusing on patient preferences.

Dr. Reed and I had been working together for a couple years at that point on some different ideas around treatment for COPD. [We began] thinking about his expertise in clinical practice and pulmonary treatments and so forth, and about how to bring these 2 things together. We thought COPD would be a really interesting venue for this study, thinking about what [are] COPD patient preferences? How do we find out about COPD patient preferences? How can we put those into economic evaluation? Of course, we really need a clinical expert to help us with that.

We started to work together thinking about the value elements that we had elicited from the first phase of our center's research. These were disease-agnostic value elements, elicited from stakeholders across a number of conditions. Once we had established that list, the idea then was to find out amongst COPD patients which ones were most important. That's where Dr. Reed and I collaborated on putting together some instruments to start to ask patients about these value elements. What does it mean for somebody with COPD, why are they important, and how can we put together some instruments to elicit that?

We also collaborated with the COPD Foundation in this work. We had a person who was in a pretty major leadership role at the COPD Foundation as an author on this study. Her experience with COPD patients over many years and understanding their access issues to medication really helped us to enlist some key patient stakeholders in the study itself and think about how this work would potentially affect COPD patients in terms of accessing medications. That's one really important reason why we conducted the study in the first place and also why we worked with COPD Foundation specifically: to get some of their insight and make sure that we were considering things that were really of importance to these patients.

Reed: From my perspective, it's been really great to work with Dr. Slejko and her group on this project clinically, as well as from a research perspective. Prior to working with Dr. Slejko, I was always struck by the variability that we see in the COPD patients, in terms of what it is that really bothers them and what really impairs their life on a day-to-day basis.

One example that I sometimes give people is hospitalizations. When we do our efficacy testing for various therapies, we usually look at hospitalization as a bad thing. But there are some COPD patients who are so scared and so challenged at home, they actually look at hospitalization during periods where their breathing is really bad as a good thing, as a safety net. So, avoiding hospitalization, while usually reflecting patients doing better, sometimes isn't.

I think it's been really nice to have an opportunity to take a scientific approach to delve into the mindset of a variety of patients that have this problem, and understand what it is that bothers them, so that we can focus on those things to address as we take care of them both in the clinical realm as well as in designing future research studies.

AJMC^®: Which aspects of COPD treatment did the patients rank as the most important? How can these findings be translated into either current or future treatment paradigms?

Slejko: We asked [patients] about a number of what we call value elements. There are about 40 of these. They were distributed among 3 main categories: treatment-related factors, outcome-related factors, and care process factors. As Dr. Reed mentioned, it's really interesting to hear about what patients really care about. Some of those results started to emerge really quickly in the first phase of this. Then, of course, the goal is then to figure out from my perspective, how then can we better fit those into economic evaluations?

If we're thinking about the treatment-related factors that patients talked about the most, or what they ranked to be most important to them, they mentioned side effects as being one of the main things that they cared about when they were thinking about their treatment. Then we asked them about what side effects mean to them, or how does that manifest in the way that they make decisions. That was the second phase of our study: to understand what that means to them. The way that they describe that is that "It might lead to changes in medication" or "Do I have to substitute one medication with another or add something else to my regimen?"

There were some concepts around regimen complexity or substituting things that would have to be done to deal with those side effects that they might be experiencing. Another thing that was really important to them, that overlapped with the care process factors, was relationship with provider. Also, concepts [were] similar to the side effects one, but regarding medication frequencies. So again, "How complex is the regimen?" or "Are there more convenient options that I don't know about? Will I find out about them?"

Reed: An additional thing to point out here is that our research is not done. We've done some good work, and we've taken some initial steps here, but there are future directions that we need to take. Clinically, what we see when we take care of patients with COPD is that lumping all patients with COPD together as a single group is a bit naïve. There are going to be clusters of people that value various elements differently than others.

The obvious [example] here would be a patient who has very advanced COPD and is essentially homebound and a pulmonary cripple. [They’re] going to have a whole different series of life experiences than patients that have COPD that bothers them but they're still functional, they're still able to leave the house and participate in society and have a job. In future steps, looking into these value elements and how they cluster around different types of COPD patients is a direction that we will likely need to go.

AJMC®: The study found that patients with COPD prioritize outcomes that are not typically measured in trials. Can you elaborate on this and explain some of the limitations of patient-reported outcomes?

Reed: In clinical trials, we look at a number of outcomes. There are actually ongoing efforts to evaluate what outcomes would make the most sense to look at in clinical trials […] Historically, things that have been looked at have been survival. Survival always matters. But even before you get to survival, you can look at things like measures of how short of breath you are, assessments of the lung function itself as measured through formal pulmonary function testing. But that doesn't always correlate perfectly with the experience of the patient.

One other factor that's been heavily looked at as an outcome measure in studies, because it's fairly easy to capture, is COPD exacerbation. An exacerbation of COPD is really a symptom change that triggers a treatment response. That treatment response could be to give the patient antibiotics and steroids or to hospitalize them. That exacerbation outcome has been looked at very closely for a number of reasons.

One being that it's fairly obvious that it happened; it's easy to say that someone experienced an exacerbation. Two is quite simple: it does affect people's lives. But it's extremely expensive. COPD is one of the major cost drivers for American medicine expenditures, and exacerbations are the primary driver of those costs. Between direct and indirect costs, it's over $50 billion a year that can be spent in dealing with primarily these exacerbations of COPD. There's a real economic motivation to look at these for the good not only of the patient, but for society in general.

But I think what some of the work we've done here is to show that there may be things that we're missing when we focus on just those outcomes. There may be things that have significant influence on the experience, from day to day, on the lives of folks, that don't translate to those more severe outcomes that we often measure, and may be meaningful, may matter a lot to the lives of people.

Slejko: A couple of really interesting points have been raised there and regarding what patients care about on a day-to-day [basis] versus what's collected in trials. Another aspect of that is then, what makes it into economic evaluation? As Dr. Reed mentioned, there are certain things that are very often collected in trials, like exacerbations, and for good reason: because they are a major economic driver and a big driver of your cost-effectiveness findings.

But then when we do ask patients about what's important to them, some of these outcome-related factors, there's really such a focus on physical abilities, maintaining social activities, fatigue. So of course, those might be intertwined with some of the outcomes that are measured in trials, like lung function. Those 2 things might be very much tied together, physical abilities and fatigue. But the way that we operationalize those in our cost-effectiveness study may not capture all the impacts on patients.

That's really part of the next phase of what we need to do. We found out some really interesting things here, but that work is certainly not done. Because really, what we hope to do is figure out how to translate these things into our value assessment. How that circles back to what's included in trials, I think, is also a very important area of inquiry right now.

To talk a little bit about next steps, there are certainly different types of patients. And that's exactly what the next phase of our study is going to do. We've already worked to put together an instrument to quantify some of the attributes that we asked about, a kind of handful of the most important attributes. We've designed a stated preferences instrument to quantify which ones are more important and how much more important. Through that you can look at groupings based on the heterogeneity of those characteristics as well. We can use the quantified preference data to look at subgroups of patients based on either their preference type and/or some of their other patient characteristics. It really speaks to that heterogeneity of COPD patients.

AJMC®: Can you discuss some of the long-term health and economic burdens of COPD in the United States and how this research addresses some of these challenges?

Reed: COPD is very, very much tied to the COVID-19 pandemic. I think it's really fascinating what kind of a marriage there is here. We looked at our own COPD population in the Maryland system and found something interesting that was observed in other systems as well. That is, during the COVID-19 pandemic, there's been a tremendous decline in people who were admitted for COPD exacerbations.

In my own clinical practice, as well, the patients that I have with COPD are frequently telling me, "I've never breathed this well in my life. I'm paralyzed [by] fear and staying home and hiding and there are aspects of my life that are worse along those lines associated with the pandemic. But from a breathing perspective, I'm great."

When we looked at it closer, it really looked like this was probably because patients with COPD are so frequently bothered by recurrent community respiratory viral infections, and the one thing the pandemic has done is really eliminated those. This is the lightest flu year that we will ever see in our lives most likely. Other respiratory viruses that we typically see, where people are just getting a cold every few months, are just not here.

I think that we're kind of in a new age of breathing without these respiratory viruses going around. It's really changed a lot, the experience of the COPD patient, in particularly in the winter months. [It will be interesting to see] how that's going to change when the limitations that have been imposed on us all and embraced by us all are subsequently lifted.

If we emerge from the COVID-19 pandemic only to enter a new flu pandemic, then I think maybe we've learned nothing. Hopefully we can channel some of the good aspects of breathing and maybe appropriate mask use in the future and translate that into improvements in the care and the health of the COPD patients in general. It may be that the experience is just fundamentally changed now. I think that there's a lot of interesting work that can be done, to look at what it was exactly that drove that change, and where we're going to end in the future, as we come out of the current pandemic.

Slejko: I think going forward, just a little bit of a different angle to Dr. Reed's response, is thinking about the future of value assessment for COPD. As new treatments do come online, thinking about whether our assessments are going to be able to address things that patients derive value from. Maybe that's thinking about how we incorporate measures of physical improvement into our value assessments and some in the clinical trial outcomes as well. Also thinking about things that perhaps aren't commonly included in COPD cost-effectiveness studies.

Side effects are not something that we oftentimes see in cost-effectiveness studies for COPD treatments. But it turns out, this is something that's important to patients. It might really manifest itself later on in terms of adherence to medication and eventual outcomes. I think where we'd like to really focus is then, if treatments aligned better with patients' preferences, are they more adherent to them? Does it work better for them, and does that eventually bring more value by aligning treatment with patients' preferences?

That's something that I'm very interested to continue working on, and really glad that we'll be partnering together on creating this preferences instrument, and working with COPD Foundation to really tackle some of these issues around assessing value that include what's important to patients and supporting their ability to access what they need.

AJMC®: Do you have any final thoughts you'd like to share?

Reed: Working with the COPD Foundation has been great because the COPD Foundation itself has a lot of folks with COPD directly involved. It really allows us to tap directly into the patients themselves as not only participants in the research, but actually functioning almost like engaged researchers.

In the history of research, people involved can be referred to as "research subjects." I think that's a term that we avoid now, particularly in the line of research that Dr. Slejko and I are involved in. We don't look at people who are participating in research as subjects at all; they aren't being subjected to research, they're participating. We call them participants, because we're working directly with them as engaged stakeholders, people who have skin in the game and really care about the research. Without them, we couldn't make any of this work. It's both with them and for them that we do this work that we do.

Slejko: I agree with all of that. I would just emphasize the role of the COPD Foundation in this particular study and going forward. In fact, they have such a huge role in some of the big studies that are going on now. Even pragmatic clinical trials where it's more studying what patients get in the real world. They have patients as co-investigators on those studies. It is a really exciting way to think about conducting research that's going to have an impact in a way that we believe is really important. That's one of the main missions of the PAVE Center […] We want to find out what's important to patients, include them along in the research process, and then think how to circle back and make sure that what they've told us is important is included in economic evaluations and value assessment going forward.