The Future of Gene Therapy in Health Care: A Conversation with Dr. Steven Pearson

Interview by yewon lee

https://doi.org/10.56927/796915

HHPR Associate Editor Yewon Lee interviewed Steven D. Pearson, MD, MSc. Dr. Pearson is the founder and current President of the Institute for Clinical and Economic Review (ICER), an independent non-profit organization that conducts evidence-based reviews of health care interventions, such as drugs, devices and diagnostics, that help patients, doctors, and everyone else in the healthcare system know what works. Dr. Pearson received his medical degree from UCSF, completed an internal medicine residency and research fellowship at Brigham and Women’s Hospital, and obtained his Master of Science Degree in Health Policy and Management from the Harvard School of Public Health. Dr. Pearson is also a Lecturer in the Department of Population Medicine at Harvard Medical School.

Yewon Lee (YL): I want to start off broader and ask about your career motivations, when and how were you first interested in researching the challenges and opportunities involved with health policy and ethics?

Steven Pearson (SP): So I did become a doctor, I trained as a doctor, and but my undergraduate major was actually in history and the humanities, I had a double major. And it probably meant I was conflicted a bit in a way. But I always realized that I thought that health and being a doctor was a lot more than just the bio science of it all. And so my interests kind of grew over time, I spent some time kind of on an internship over in England, seeing how they provided medicine and that healthcare setting. And then I did my residency in Internal Medicine here in Boston at the Brigham and Women's Hospital. And there, I was fortunate to be part of a brand new primary care residency, where I did my inpatient training at the Brigham, but outpatients was at what is today called Harvard Pilgrim health care, but back in the day it was Harvard community health plan. And that's where the doctors were actually the same thing as the insurance company. So we had to see patients during the day, but then in the evenings, we would go sit in a conference room, and decide which drugs to cover, which new machines to buy, which staff personnel, buildings, all these decisions and trade offs about the finances of healthcare, as well as the clinical stuff. So I became really interested in the intersection of the ethical challenges of making those decisions, because you're always, in some way, making decisions with limited resources. So by saying yes to certain things, you're kind of saying no to other things, whether you realize it or not. And ultimately, the way that we make those decisions has a lot to do with whether people can afford health care at all. So it all kind of wrapped up in my mind as something that we needed to do better as a country, not just, you know, in this one health insurance company. So I started a Center for Ethics and managed care at Harvard Medical School, and just continued my work in this area until I decided that I really needed to start an independent Institute, that even being an academics, it was okay, but we for a while we were based over at the Mass General Hospital, and people thought we should be really independent, as we know of all the systems of care. So I started the Institute for Clinical and Economic Review, or ICER, which is today a nonprofit Institute, and we do assessments of new treatments like gene therapies. But our back kind of our real mission has always been to, to bring to the public, and to decision making a more transparent and honest approach to thinking about value, about the effectiveness about the budget impact about the long term value, and just basically engage everybody in a more transparent decision making process about how we do the best we can with limited resources.

YL: Thank you so much. Could you tell us a little bit more about ICER? Are there any perspectives about health policy that have maybe changed since you founded the ICER? Or maybe any, like unexpected events, whether that be COVID? Or, like certain drug approvals?

SP: Yeah, well, I started ICER, back in 2006. When I started, it wasn't to address a particular part of the health system, like drugs or surgery. It was trying to kind of create a laboratory in which we could deal with anything that was kind of difficult at the time. And so probably what's changed the most is just, I think, our health system, as it has evolved. There have been different phases, or different types of innovation created the biggest questions about the evidence and about the value and about fair pricing. So in the early days, that was more around rating versions of radiation therapy, because there were these very expensive, new machines, and people didn't know how they should fit into the healthcare system and what the fair price would be. And there were other kinds of innovations around surgical devices like robotic surgery that we looked at. But then about, I guess, eight years ago, and this has been true for a little while, it became clear that new drugs were becoming the biggest problem. They were the area with the fastest increase in spending. There was great innovation, and that in a weird way created the problem. There were some really great new treatments for hepatitis for cancer. But the price tag for these things was just skyrocketing. And in part that was because in the drug area, we are the only developed country until very very recently that had no government involvement at all in. Looking at the evidence and deciding whether it should be covered by insurance or what the fair price would be every other country, England, Germany, France, Italy, Spain, Canada, Australia, and all the if you will, kind of higher income countries, were doing this at a governmental level, we were not. And that kind of gave a blank check to drugmakers for them, and consequentially our pricing in the US was much, much, much higher. So we started to do more reviews there. And I guess that's kind of our biggest profile now, kind of as the new drug price watchdog is what we're often called. And it's partly again, because our government. Medicare— there was a law passed just a couple of months ago that will allow Medicare to negotiate the price of a couple of drugs long after they've already been in the market. But we're still the only group that's doing a consistent approach to looking at fair pricing when drugs are first introduced. And there's still a lot of questions about their effectiveness. But at that time, that's when their price gets set. That's when insurance companies decide whether to cover them or not, and how to cover them. So that's kind of been our sweet spot. And it's still the place, I think, where our country will be wrestling for a long time, because the innovation has been spectacular, and I hope it continues to be, but we have to be able to do it in a responsible and ultimately affordable way.

YL: I want to transition into one of the articles that you co-authored on the evidence and value of gene therapy that I found was really fascinating, especially at a time when new technologies like CRISPR are being uncovered to be able to manipulate the human genome. So for context, how would you define gene therapy and sort of its benefits?

SP: Gene therapy is one of a set of one time treatments in general, that seek to address the underlying kind of mechanism that causes the disease or condition. And, for a lot of conditions like hypertension, there's not one gene it's in. It's a very complicated kind of pathophysiology that causes high blood pressure. But for some conditions, especially rare conditions, it's often just one gene that has a defect. And if you can go in, and our technology is now allowing us to do that, you can go in and either snip out that bad gene completely, or even replace it with a good version of the gene. There are different ways that gene therapies can do different types of approaches to conditions. But the issue is that this raises the potential of a real cure. And so all of a sudden, we've got the great opportunity to benefit from treatments that could save lives, in some cases from fatal conditions. In other words, it might help disease and not let it get worse. It might help us save money, even by reducing the use of very expensive treatments for many, many years. If you can give one treatment, and cure the patient and get rid of all that. At the same time. This creates tremendous questions around how we pay for these things. Because if you do give a one time treatment, you may not know how long the benefit is going to last. And so you can assume it's going to last for the rest of the patient's lifetime. If you do that, you're probably going to end up thinking that it should be worth a lot of money. And might be but we have a lot of questions around whether we should pay for it all at once or over time. How much uncertainty do we build into what a fair price would be? And also, just because our insurance system is so awkward, in some ways, it has a hard time figuring out how to pay for really expensive one time treatments. It just makes it really hard for employers who are paying most of the insurance premium to be able to do that in the short term for a person who might not be their employee, you know, for the rest of their lives. And so who gets the real value out of this really expensive one time treatment? All of those problems, in a sense, combined with the great potential for gene therapy, make it one of the most fascinating areas of our healthcare system today.

YL: For sure, and we've seen a lot of early evidence of gene therapy pricing in places like Europe. How do we expect to see gene therapy be accepted within the United States healthcare system and especially within United States health care plans?

SP: Well, there is already some early stress in these systems in Europe. There have been a couple of high profile situations where the gene therapy worked, but the government couldn't come to any agreement with the companies that owe her a price. And so the companies decided, no, we're not going to offer our gene therapy in Germany or in France or in England. And so you kind of think that that's a lose lose proposition. The gene companies are generally thinking that they're going to make most of their profits, as they do on all drugs here in the United States. But here, again, you know, how much of that can we absorb all at once. So as long as the gene therapies have been coming in, in a drip, drip drip fashion, like a little bit, for a small number of patients, these are now costing more than $2 million a year, we're anticipating very soon, they'll begin therapies that are more than $3 million for a one time treatment. As long as you just have a few patients, you're doing that with a big insurance company that can manage it. But if we suddenly get five or 10 gene therapies in a single year added to the cost structure, and especially when those gene therapies in some cases are now going to be treating much more common conditions like high cholesterol. Now, you can't charge $3 million a person. And so you've got all different kinds of questions around. Where's the threshold? Where's the tipping point? You know, how long can we go with this very, very high priced approach, paying all upfront? Are we gonna have to figure out some way to either pay it over time, kind of like on an installment basis, or also just make sure that, you know, the pricing does align with the benefit. And that's a lot of what my Institute does, because gene therapies aren't all cures. It's really kind of strange to think that way. But you can, you can address the genetic problem, but still only make the condition a little bit better, because sometimes we can't really fix it completely. So, but sometimes you can, so we want to pay a lot for a treatment that really is a cure for a very complex, expensive, maybe fatal condition. But that doesn't mean we're going to spend $3 million on every gene therapy. And that's the that's the question is that, in our system, where the government isn't involved in negotiating those kinds of treatments, yet, it's hard for the companies to hold off charging as much as they can, which right now is around $3 million, even if their drug is just a little bit better than other treatments. So we're really wrestling with this question of value and affordability. And these companies, they do need, you know, they need to make a return on their investment and on their risk. So all these forces are part of what makes this an ethical as well as a business as well as the scientific challenge.

YL: And as we sort of see these gene therapies enter the market, do you see a potential for maybe greater, like inequity or disparities between people with rare diseases who are able to afford versus those who aren't, as well as, like, drive research funding away from more accessible medicines?

SP: That's a great question. We actually have public meetings with every single one of our reports, because again, our mission is to bring the public in and make this whole process more transparent, rather than having drug companies and insurance companies in some back room. And as part of that process, we introduced a vote. Regarding equity, you know, will this treatment help us address health inequity in our system? And what's interesting is that the debate almost always focuses on the fact that any new treatment in the US healthcare system, almost by default, will make equity or worse, it will make greater disparities, because who gets new treatments, people who are have better insurance or more plugged into academic health centers are usually wealthier. And so who doesn't get the new treatments more often are people of lower income, who often live in, you know, diverse communities of color, etc. And so we have a real problem. And Gene therapy puts almost all of those into highlight, because you've got something that's very expensive. It might only be administered by specialists at an academic medical center. And so that might drive greater disparities in access, and outcomes based on you know, a lot of these other factors that I talked about. So we are not on a great path there. We do, you know, given the expense here and given our private insurance system being fragmented the way it is. It's not that easy to see a short term answer to this problem. But it is something that we have to really keep our eye on because, and health insurance companies are trying to do a better job of understanding how their policies affect access and equity across different kinds of communities. But we have a real structural problem, both with racism and with the kind of equity linked to income and other ways as well, that we are not going to easily overcome and gene therapy is only going to probably make it worse?

YL: And would you say that there are certain solutions to the affordability and accessibility issues associated with gene therapy?

SP: Yeah, in my mind, the solution has always been that everybody has to kind of step up and assume responsibility. Because this all has to work together, it has to start with companies being willing to moderate their prices. And again, that will have to be in some relation to the uncertainty about the effect of their drug, or therapy, how many patients are going to get it. I mean, we don't have a system where somebody's going to say you can only make this much profit and not a penny more. But we have to have some moderation from the drug makers themselves. Linked to that, if we can get reasonable pricing, then the insurance companies need to step up. And they have to realize that their job is not just to say, yes, it's covered by insurance, they might have to go out of their way, they might have to say, You know what, we need to create new virtual kind of telehealth platforms or something to allow people in rural communities, or lower income communities to have equal access to this, we might have to push out information to clinicians in those communities, instead of just being passive and letting it kind of happen the way it's always happened before. And patient advocates who play a surprisingly powerful role in Washington and other places around access to these drugs, they need to realize that just getting the big insurance companies to cover it is not the end game. They too have to really think get involved with equity and start to think about the voices in their patient community who do not often get invited to the table and figure out how they can advocate for them as well. So that all of this system can shift and innovation can be more fairly disseminated and made available to people.

YL: And how would you sort of assess which solution is right? As in? How do institutions sort of find the right balance between the incredible benefits of gene therapy versus the equity issues?

SP: Ah, that's a great question. They're kind of procedural. But they're, I mean, what's funny is that, you know, I know a lot of different drug companies and insurance companies over time. And they're surprisingly different from each other, their cultures, their own internal kind of thought of what a good outcome looks like, is very different. And some of them really do have much more of a social consciousness mission in mind. Generally, that's linked to a kind of a longer term view of their relationship to society, instead of just a short term relationship with their shareholders. So in link to that, as the idea of humility, some companies get very, very proud of their science, for instance, you know, they're very proud. We created the first therapy for this rare condition. There they are, they're justifiably proud in many ways. But if they translate that pride, into a kind of hubris over you know, and therefore, we should be mega wealthy, and charge anything we can. And they don't really kind of think about the broader social implications of how they're pricing their product, and we've really kind of lost an opportunity. So, you know, what we try to do, at least is to provide an external kind of independent voice that can say, hey, you know, before you name, your price, here's what kind of an alignment of the pricing with the added benefits to patients would suggest as a fair price in the US context. Now, we don't have any power, other than the power, I guess, of holding a mirror up to the industry and saying, here's an independent view of what's fair, if you're going to charge more than that, justify, justify it to everybody and don't do it just with kind of vague terms really kind of come to the table and justify it. So we're trying to hold them to account and we're trying to hold the insurers to account on the other side as well. So we have this kind of middle ground, I guess you could call it where we're trying to speak to all the key powerful stakeholders using science and public engagement given that our government has chosen so far not to really do that job. And again, in other countries, the government does this and you can understand why it's a pretty important role. It shouldn't be accountable in some ways to somebody else. We do it as an independent group. But I've honestly often thought, since day one of ICER, that the ultimate goal for us is to get eliminated, that maybe the right thing is for our country to realize that this is something people and we as a government need to take on. Of course, Americans don't trust their government to start with. Many Americans don't really like the government getting involved in business or in health, for a variety of reasons. So maybe we'll just keep muddling Through the way we're doing it, but I am worried, I think Gene therapy is going to be brilliant. And we're going to hear all these great cases of individual patients being cured. And we'll probably hear from headlines about the pricing. But as always, we won't hear as much about the people who really are not able to afford it, not able to access it. And whose access to health care overall might be affected, just because every time we add something expensive to the package, everybody's health care insurance costs go up. And over time, that just creates real pressure on lower income Americans to be able to afford their basic health care needs. So we have to get a better balance.

YL: And on a more personal note, do you see some of the stakeholders involved with gene therapy differently, as a result of your experience as a physician?

SP: I guess it's linked again to this idea that I mean, I've always thought that physicians also have a challenge, our short term, if you will, or primary goal, or focus is the patient in front of us. But I've always felt that our professional as clinicians, and not just doctors, but this is everybody involved in the healthcare system, we need to think about the patient who's not in the room today, but might be tomorrow, you know, the person who's in our health system in our community, we're all we have to just view this, that we're all linked together. Even if we're not on the same insurance plan, or whatever, we all actually are linked in this community, in which we have to figure out how pricing and access can fit together. And I guess, as a doctor, that means that I share the thrill of innovation, and the thrill of thinking that we have this new science that we can, it's brilliant, the science is brilliant, and I really respect the dedication and risk taking of companies and individual scientists. But I do think that we all have a broader ethical mission, if you will, a broader ethical responsibility to people. And so my hope is that we can, again, kind of spread a sense that that's the right thing for companies to do, that they can have a short term focus, and a long term focus, and that we can blend that in a way that will work. And that's the experiment that we're still on.

YL: Thank you so much. And policy always tends to sort of follow behind scientific innovation, a lot of the times because of the lack of proper scientific communication. So what would be some ways that ICER has sort of implemented to bridge that gap, and promote, like greater dialogue about the topics?

SP: Another really great question, because we've really wrestled a lot of our work in because when we're assessing the evidence, for instance, from clinical trials, it gets very wonky, very technical, very fast. And for our work to be viewed as state of the art from an academic perspective, it can't really directly communicate it to patients or the public, it's too technical. And so our challenge is, so what do we do? So we do, I mean, we do, we've developed a language around value that is different than what was being talked about before, you know, value before was either profit margin, or, you know, the cost of developing the drug. And value really now we've helped I think, change the way that people are talking about it, talking more about value is, does the cost or the price align with the added benefit to patients? And how do we think about that benefit. And if you say, benefit to patients, and you say that to a patient, or a family or an advocacy group, now they feel like, oh, I can have that conversation. Let me tell you how this drug benefits me. It's not just because I can move my arm better, it's because that lets me take care of my family or go to work. And so we start to have a broader view of what benefit means. And that's the kind of engagement and conversation around value that matters. I also think it's really empowering for people to feel like there's a forum to come to talk about these issues, because, again, patient groups have power, but they often feel like they're constantly in a kind of antagonistic relationship with insurance companies. They're usually aligned with the drug companies because they want more innovation. And that's a good thing. We're trying to change that dynamic to where patient groups feel like they have a voice and responsibility to exercise it around pricing and around the way that that ultimately affects their ability to access and afford something. So we're still again, I think, in relatively early days, but we try really hard to create versions of our reports like executive summaries and others that can be read by lay people who don't have to know all the jargon but the Biggest influencers just trying to get people into the room to have a conversation using the language that they're comfortable with?

YL: I think that was a great question to sort of end on, I want to thank you, again for lending me your time. This was incredibly insightful. And I think our readers will really enjoy and want to learn more about gene therapy. So this was incredibly insightful.