RARE Daily

Determining the Value of Rare Disease Therapies

April 4, 2024

The small patient populations of rare diseases, the limited natural history of these conditions, and the lack of long-term experience with new treatments all contribute to the difficulty in determining the value of rare disease therapies. The issue can be further complicated by whether value is calculated in a single payer system, or a multi-payer system. Recently the Innovation and Value Initiative issued a report with the Everylife Foundation for Rare Diseases from a long-term project to bring together stakeholders to explore patient-centered outcomes across rare diseases to inform those discussions. We spoke to Rick Chapman, chief scientific officer of the Innovation and Value Initiative, about the challenges of assessing the value of rare disease therapies, the role qualitative data should play in value assessments, and the recommendations from the report.



Daniel Levine: Rick, thanks for joining us.

Rick Chapman: Thanks for having me.

Daniel Levine: We’re going to talk about the work of the Innovation and Value Initiative, how various stakeholders think about and calculate the value of therapies and the challenges for doing this with regards to rare disease therapies. Let’s start with health technology assessments. For listeners not familiar with that term, can you explain what these are and why they matter?

Rick Chapman: Health technology assessment, and it’s often abbreviated as HTA, is really an analysis of the clinical and economic value of a particular healthcare intervention, and that could be a drug or surgery or any other type of healthcare delivery. And to do these analyses, we really try to bring together various factors such as the cost, the safety, and the efficacy of these interventions. And it’s used by employers, payers, manufacturers, and policymakers among others to help determine how patients are treated and at what cost. And it’s sometimes called value assessment because essentially what we’re trying to do is assess the value of a new technology.

Daniel Levine: Well, how are these typically done for a new therapy? How is value generally calculated?

Rick Chapman: So usually assessments include at least two components, two major components. One of these is the comparative effectiveness research, so really just trying to say compared to treatments that are already out there for this condition, how effective is this treatment? Is it fulfilling some unmet need or is it providing greater effectiveness than what we already get from current treatments? And then that’s often supplemented by an economic analysis. It’s often a cost effective analysis looking at the cost per life year or cost per quality-adjusted life year. In some cases you see more disease specific measures like cost per remission or cost per case avoided. But really what you’re trying to do is say, “okay, how much bang are we going to get for this treatment?” And then given the cost, how much bang for the buck are we going to get? One thing I’ll point out is that when we’re doing these assessments, it’s important to think about the perspective. So, when you think about value, value to whom. Is it to the patient or the payer or to society overall? And another thing I think we need to keep in mind when we do these types of assessments is that we need to make sure that the outcomes that we’re looking at and using to measure the effectiveness are things that are important and matter to patients.

Daniel Levine: What makes doing this for a rare disease therapy challenging compared to say a treatment for a large market indication or one where there are already existing therapies?

Rick Chapman: Rare diseases by definition have a smaller number of patients than more common diseases. So that really is what leads to a lot of the challenges in looking at treatments for these rare diseases. Because they’re smaller numbers, it makes identifying and recruiting patients for studies more difficult. The design of the studies themselves is often more difficult. A lot of these rare diseases, we don’t know a lot about the natural history of the disease. There’s often a lack of standard treatments for these diseases. And so it’s difficult to have something to compare the new treatment to. And for some of these diseases, especially ones that are rapidly progressing and deadly, there may be difficulty in creating placebo arms to compare treatments to because it’s considered unethical to put patients on placebo. And so, you have to come up with different study designs to get around some of these issues. Another wrinkle that gets added to this is that a lot of the treatments, especially more recently that are coming up for rare diseases, are often cell and gene therapies. And these cell and gene therapies are revolutionary and may have dramatic impacts on patients. Some people are even starting to use words like cure around some of these treatments, but they’re also relatively new technologies. And that leads to questions about what’s the long-term effectiveness of these treatments? Are they going to continue to work for patients? And because they’re given as one-time treatments upfront, these high tech treatments often have really high upfront cost. And all of these issues lead to greater uncertainty around assessments of treatments for rare diseases and greater financial risk for those who are paying for these treatments.

Daniel Levine: The Innovation and Value Initiative earlier this year issued a report with the EveryLife Foundation for Rare Diseases that grows out of a long-term project to bring together various stakeholders to explore patient-centered outcomes across rare diseases. For listeners not familiar with the Innovation and Value Initiative, can you explain what it is and how it’s funded?

Rick Chapman: Sure. The Innovation and Value Initiative or IVI is a nonprofit membership-based research organization. And our mission is to advance the science practice and use of patient-centered health technology assessment to support decisions that can make healthcare more meaningful and equitable for patients. And one way I like to think of this is to say that we’re trying to work to raise the bar on how we do these assessments to make sure that we are including what’s important to patients. And in doing this work, we always strive to be patient-centered, transparent, and equitable.

Daniel Levine: What was the need you were trying to address and can you give a sense of who participated in the project?

Rick Chapman: So, the need that we’re trying to address here really arose from the challenges around rare disease treatments that I was just talking about before. We know there’s going to be more and more treatments coming along for these diseases, including some of these revolutionary cell and gene therapies, but we know that these assessments, because of all of those challenges we talked about, are going to be very difficult. And so, with more and more treatments coming along, we felt like it’s going to be difficult to do customized assessments for each and every treatment for each and every rare disease that comes along. And so, we were looking for a way to streamline and standardize health technology assessments for rare diseases to make sure that when these treatments do come along, there are no delays in access while we try to figure out how we’re going to cover and pay for these life-changing treatments, even with all the uncertainty involved. And so, to do this work, we partnered with Annie Kennedy and the EveryLife Foundation for Rare Diseases, and they were invaluable partners as we did this work. We were also guided throughout the project by a multi-stakeholder steering committee that included researchers, manufacturers, payers, employers, and especially patients and patient advocacy organizations. We made sure that they were overrepresented on this committee and our roundtables to make sure that we heard from diverse patient voices and included them. And then the steering committee was also supplemented by three round tables that brought in additional stakeholders for discussions around some of these issues, really with IVI as the convener here.

Daniel Levine: How much of a gulf is there between patients, payers, drug developers, and others about how to measure outcomes to determine value?

Rick Chapman: It depends on several factors, but it can be quite large and especially where clinical outcomes that are used in the trials that are done for regulatory approval don’t match the outcomes that matter to patients. So patients may emphasize disease specific outcomes that are important to them while payers and policymakers are often looking for broader measures that they can use to compare across diseases. That can lead to some tension. And then finally, cost that we include in these analyses. The costs that are important to payers may not be the same costs that are important to patients and others. For example, patients may care more about out-of-pocket costs or employers may care more about productivity loss and those things may be less important to payers. So, when you have this mismatch, it often leads to gaps in these assessments and even greater uncertainty around “are we including what’s important to patients?”

Daniel Levine: You were exploring patient-centered outcomes, what’s meant by the term patient-centered in the context of health technology assessments.

Rick Chapman: So, it really includes patient-reported outcomes, but also some outcomes that may not be reported directly by the patient may be measured in different ways, but what distinguishes them is that they’re outcomes that matter to patients and their families, that they’re helping them achieve their goals for treatment rather than the goals that are set by clinicians or payers or others outside of the patient.

Daniel Levine: In the case of a person with Duchenne muscular dystrophy, being able to have arm use for using a computer might be considered a patient-centered outcome even if it’s not part of the clinical outcomes measures?

Rick Chapman: That’s right. Often when we do these assessments, we’re looking at health and longevity, but in a broader way, we’re looking at quality of life or life expectancy, but patients may have more specific things that matter to them, just like the example you were using. Often in diseases that affect mobility, the FDA is looking for measures like a walking test. How far can a patient walk in a certain amount of time? If a patient with muscular dystrophy or some other disease is wheelchair bound, that may not be a practical outcome for them. What they may be concerned about is something like you’re talking about—can I move my arm or my hand enough to be able to control my motorized wheelchair? That may not be captured in any kind of study. And in those cases, it makes the assessment much more difficult because here is something that really matters to patients and this treatment may be helping them to achieve it, but we haven’t measured that properly. So it’s hard to include it in these types of assessments.

Daniel Levine: So, if you think of some of the quality of life outcomes that you looked at, what were they and do they have to be built into the clinical studies to properly apply them to health technology assessments?

Rick Chapman: In this work we did identify that one of the things we wanted to do was look for outcomes that maybe cut across rare diseases so that each time we come and do an assessment for a new rare disease treatment, we don’t have to start from scratch and come up with completely new outcomes. We found out that there were some outcomes that do seem to be important to patients that do cut across a lot of rare diseases, and actually a lot of them are common to more common conditions as well. So some of the things we identified were physical functioning and pain, but also mental health issues and cognitive issues that were important. Fatigue and sleep issues were also important outcomes that cut across diseases, and those are two that you definitely see a lot in more common conditions as well. But we also found some outcomes that were important to patients that we don’t necessarily associate with quality of life or at least health-related quality of life. And those were things like social relationships, employment and work issues, and other economic impacts on patients. And we identified these through a literature search in our discussions with steering committees and roundtables. So they really came through as important to patients, but as things that were not always emphasized in regulatory decisions or peer decisions.

Daniel Levine: What role should qualitative data play in value assessments?

Rick Chapman: We think it’s important to include qualitative input, especially where there are these gaps in quantitative data or where there are outcomes that are difficult to measure in a clinical trial or in a quantitative way. One of the things I recently ran across was a quote from a sociologist William Bruce Cameron, and he said, “Not everything that can be counted counts and not everything that counts can be counted.” And I think that’s important to keep in mind that there’s a lot of things that matter a lot to patients and their families that are just very difficult or even impossible in some cases to measure in any quantitative way. And so we need to keep that in mind and figure out ways to integrate the qualitative inputs with the quantitative data. And we need really better training of people who are doing these types of assessments and trials because we’re usually very much focused in our training on the quantitative analysis and not so much on qualitative ones.

Daniel Levine: One of the complexities in determining value of therapies in the United States is our healthcare system where there’s not a single payer. How does that complicate building consensus around measurements of value?

Rick Chapman: We do have fragmented systems of healthcare and it does lead to a lot of challenges in our systems. I think there’s often a lack of communication across the system and across stakeholders within the system that can lead to a lot of duplication of efforts. We often have perverse incentives that make it hard to align people’s interest in the system. There’s often information that may be siloed or stuck behind paywalls, so it’s hard to share data across the system. And all of this leads to inconsistent measurement and inconsistent decision making, which can be really frustrating for patients and lead to suboptimal outcomes. We’re not getting all the health that we could for the dollars we’re spending. And that was something in this project that really struck me when we did our roundtables and we had all of these stakeholders in the system come together. It always strikes me as how seldom we do that in our system, that we get all of these people around a table to really talk about what are their pain points, what are the issues and challenges that they’re trying to deal with? And that’s why I think it’s important to have organizations like IVI that can convene these disparate stakeholders so that we can learn from each other and hopefully get to approaching some sort of consensus.

Daniel Levine: My sense in general is people in the rare disease world want to expand the notions of what constitutes value, whether it’s economic impacts, impacts on the life of a caregiver. In a single payer system, there might be stronger arguments for applying those types of measures of value. Why should a private insurer care about the effects of a treatment on the ability of a person with a rare disease or a caregiver to remain employed?

Rick Chapman: Yeah, it’s a good question. Especially when certainly in employer-based insurance, they may have a member for three years or less and then they move on to another payer. And so it is kind of a short term focus there. But insurers’ clients are not only the patients, it also includes the employers who are providing benefits, or if it’s a public system, the policy makers who are paying for this insurance. And so the employers and policy policymakers certainly care about productivity loss from workers and their families due to these health and cost issues. So it’s something that they should pay attention to. I’ll also point out there’s also some interaction between employment and insurance status for a lot of people in our system. And so, if a patient gets to the point where they lose work and are no longer employed, the insurer may lose that patient, and if they lose enough patients, may lose the contract with the employer. But finally, I think beyond the financial reasons, I think there’s also we need to keep in mind that this is healthcare and there’s ethical obligations that once you enter into a contract to provide healthcare or pay for healthcare for a population, you have an obligation to make sure that they’re getting the healthcare that they need.

Daniel Levine: The report created a list of recommendations and ranked them based on urgency and feasibility. What were the top recommendations?

Rick Chapman: So, we had several recommendations, and for those who haven’t seen it, I would urge you to go to our website at thevalueinitiative.org and download the report and look at it in more detail. But there were two recommendations that really stood out for me. First, the importance of the patient journey. Patients kept emphasizing to us that you can’t just look at one point in time, that what matters to patients and the outcomes that are important to them change over time depending on what’s happening in their life and what’s happening with the disease that they have, how it’s progressing. And so one of the recommendations we make is that those who are developing clinical trials and other studies need to collaborate with patients and families and patient advocacy groups to make sure that they’re including outcomes that are meaningful to patients across that entire journey and not just at certain points in time, really pointing to the need for continual engagement with patients throughout the process. And then the second recommendation that stood out for me was that we really need to recognize the unique data challenges that come about when we’re looking at rare diseases and doing these value assessments or treatments for rare diseases so that we can make sure that those challenges and that uncertainty that comes with those don’t unfairly bias decision making around these treatments so that we make sure that rare disease patients aren’t being penalized because they have rare diseases—that we’re making allowances for the uncertainty that we know is going to be there. And that was part of this project, trying to look for those commonalities or analogs that cut across rare diseases so that we can hopefully overcome some of those challenges and accelerate some of these coverage decisions.

Daniel Levine: How do you move this work forward? What’s the next steps for implementing what you’ve done?

Rick Chapman: We’ve started to think about next steps. One of the things that we’re interested in is trying to develop these recommendations into a more formal framework and maybe a checklist to go with that framework that would make it easier to implement these recommendations in a systematic and practical way. And so one of the things we’d also like to do is take that checklist and apply it to a couple of rare diseases or maybe more rare diseases to demonstrate how this could be used in practice and how it might accelerate the process to assess these treatments for rare diseases. And as we go into that work, especially around the use cases, we will definitely be looking for rare disease organizations or other partners that we can work with to implement these recommendations and put that checklist and use cases together. So I’d like to put out a call to anyone who’s interested in this to contact us, and hopefully we can find ways to work together on this project or other work. I’ll also put in a plug if you’d like to hear more about IVI’s work, you can go to our website, as I mentioned, thevalueinitiative.org. We also have an upcoming Methods Summit on March 14th. That will be an in-person meeting, but we also have a livestream option. So if you’re interested in finding out more about our work, please go to our website and register for that summit and you can find out more about what we’re working on.

Daniel Levine: And since we likely won’t be live by March 14th, is this available on a replay?

Rick Chapman: I believe we are going to be recording it. I’m not sure exactly when it will be posted, but there will be some posting of the recording afterwards.

Daniel Levine: Rick Chapman, chief scientific officer of the Innovation and Value Initiative. Rick, thanks so much for your time today.

Rick Chapman: And thanks so much for giving me the opportunity.

This transcript has been lightly edited for clarity and readability.


The RARECast podcast is made possible through support from the Global Genes’ Corporate Alliance. The members of the Corporate Alliance support Global Genes’ mission and programs, work to meet the vital needs of people with rare diseases, and address inequities they face. To learn more about the Corporate Alliance or how your organization can become a member, click here.



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