 Our first speaker is Dr. Andrew Aronson. Andrew is an assistant professor of medicine in the Center for Liver Disease in the section of GI at the University of Chicago. Dr. Aronson is also a faculty member at the McLean Center for Clinical Medical Ethics. He's the co-principal investigator of HEPCAT, which is a CDC-funded initiative to diagnose and treat hepatitis C in the Chicago area. This project utilizes telehealth technology to expand hepatitis C management into the primary care setting. Dr. Anderson runs a very busy clinical practice, including both general and transplant hepatology and writes often in the field of ethics of transplantation. Today, Dr. Aronson will speak to us on the topic of the true cost of hepatitis C therapy. Andrew Aronson, welcome. Thanks, Mark, for having me and inviting me. This is a great conference every year, and it's a real honor to be here and to present some of this to you. So I'm gonna talk a little bit about hepatitis C therapy, which you've probably heard a lot about in the news recently, and my goal is to kind of give you a little bit of a background of what's going on in hepatitis C, but also identify some very unique ethical issues that are happening at the same time. I don't have any disclosures or conflicts of interest. So by means of a background, hepatitis C is a very, very prevalent, both in the United States and worldwide. There's about 5 million people in the United States that are infected, about 180 million people in the world. And in the United States, it's a leading cause of liver cancer, liver-related death, and transplantation. So really a huge burden to our society. What's making this very interesting is that there's very new therapies that are very effective that have come out in the last couple of years. This is really where the crux of these ethical issues is starting to come out. So a lot of people say to me, so I specialize in hepatitis C, and a lot of people say to me, you know, I saw a commercial where now they can cure 99% of people with a pill. What are you doing? And I said, you know, that's a good point. It is a pretty easy thing to cure now. But I kind of refer people to this. So it turns out that, since there's so many people that are undiagnosed, and there's so many people that have it that have not been treated yet, we've actually only begin to see the mortality in our country that's related to hepatitis C. You can see here by the year 2030 or 2035, we're expecting about 35,000 people a year to die of this disease. This is actually a model, this is one of many models, but this model actually includes new therapy. So this is including all these people very easily being cured from this disease. To kind of understand the ethics, I do wanna review just a little bit of the physiology of this disease and the pathophysiology of this disease. Hepatitis C progresses very, very slowly. So patients are infected with hepatitis C. The majority of these patients are gonna develop a chronic infection. And over time, that inflammation of the liver will cause fibrosis. And over years, usually decades, that fibrosis will get worse and worse, which will result in cirrhosis for most patients, for many patients. Once a patient develops cirrhosis, they're at risk of developing liver cancer. They're at risk of decompensated liver disease and they're at risk of dying from their liver disease. This entire process, in most cases, will take 20 or 30 years from the time of infection to the time a patient's having significant medical issues for it. Now, it turns out that after all of this, hepatitis C is a very wimpy virus. It's very easy to cure. It's not like hepatitis B or HIV where we suppress the virus or we kind of put it down for a number of years. You can actually cure hepatitis C, meaning the virus can be completely eradicated with medical therapy. And SVR is a terminology that we use that will sustain virologic response and that's complete viral eradication. And when people have an SVR, of course the virus goes away, that's the easy part. But what we know is actually the liver will get better in a lot of patients. So some of that scarring that I was talking about will go away. And this results in improved clinical outcomes. So there's lots and lots of studies over the years that show when people have an SVR, their chance of their liver decompensated nearly goes to zero. Their chances of developing cancer nearly goes to zero. And all-cause mortality goes down, both liver-related and all-cause. So patients are going to significantly live longer if their virus gets cured. There's really no doubt about that. So we've come a long way in hepatitis C therapy. And you can see, and this is going to be an important kind of graph to kind of put in your mind as I'm going through this, of how far we've come over the last 30 years. So back in the mid-80s, the only therapy that was available was a drug called interferon. An interferon is an injectable medication that is extremely toxic. So if anyone here has had a patient or knows a patient that's been on interferon, it's almost always a miserable experience. There's flu-like symptoms, depression, problems with blood counts. Patients really do very, very poorly. And in the mid-80s, we knew very little about hepatitis C and interferon therapy, you'd make your patients miserable and you'd only cure about 6% of them. So it wasn't so good. This was tweaked over the years and in the 90s we used a different formulation of interferon. We added a medication called Rhinoviren. But even at the best, and then this is in sort of the early 2000s, we were only able to cure about 50% of patients. And there's a caveat there that this is only the healthiest of those patients. So if you had any comorbidities going into it, you probably weren't going to be a candidate for therapy anyway. So this is a highly selected population and of those, you made them miserable and you could only cure half of them. 2011 was a very big year in hepatitis C. And this was the year of the first direct acting antiviral agent. So this is a drug that actually works on the virus itself. Everything we had prior to that would work on the host response, the patient's immune system to fight the virus. This is the actually first directed therapy we had. And everybody was very, very excited because you can see this is our first big jump. So now we can cure 75% of patients. This was great, but you still needed interferon. You still needed Rhinoviren. And this drug itself happened to be very, very toxic. If anyone is familiar with HIV therapy or took care of patients when HIV was first started to be treated, this was like the first generation of the antiretroviral medication. It kind of worked, but really, really toxic. And then fast forward to today. So in 2015, we have a therapy for most patients with hepatitis C that is one pill, once a day with about a 90%, 95% curing. So essentially we can almost cure everybody with a side effect free medication that is very highly effective and extremely safe. So where are the ethics here? This is great, this is success. This is modern medicine doing what it's supposed to be. And what I wanna kind of propose to the group today is thinking a little bit about ethics of success. So when we think about some of the ethical questions that we deal with all the time, there are really reflections of limitations of understanding that we have, whether it's understanding of medical science or mechanisms of disease, think of end of life issues. So when you're having an end of life issue with end of life discussion with the patient, ethical questions come out of, we really don't know what's going to happen to that patient. You know, we've reached the end of our therapy that we're able to save the patient. You know, we're dealing with our limitations and that's when these questions come up. Even if you think about it, maybe a bit of a stretch, but informed consent is actually acknowledging our limitations. We're saying, I'm proposing to do this procedure. You know, some stuff could happen. I'm not sure what it's going to be. There could be some complications. You could react a certain way to this procedure. I don't really know. It's acknowledging limitation. But what about when science wins? I mean, this is a win. Science has won. You know, we have come up with medications that have completely eradicated this disease. No side effects, easy to take. There's no reason why anyone that walks into my clinic can't be cured. Is there ethics when science wins? And I want to show you that there certainly is. So there's two bottlenecks. And a lot of these ethical issues of science winning really deal with resources and limitations of resources. And I want to tell you two stories. One, which happened in 2011, coinciding with that first jump. And the other one that's happening right now. So there are these two very telling issues of limitations of resources. So we'll go to a little bit of a historical break in 1922 when insulin was discovered by Banting and Best. And they were able to isolate insulin from livestock pancreas. And of course, here's a picture of them. There's only so many livestock pancreas that you can get your hands on in 1922. So there was a limitation. They could only make so much insulin. So what happened, they were able to make insulin. It was working for diabetic patients. Their friends got it. Very well connected people who could travel were able to get it. So it was only sort of divvied out to these people. So as fast as they can make it, just kind of this highly selected group were able to get it. And of course, this violates justice. Certainly patients didn't have equal access to this medication who needed it. And also you can make an argument that violates utility. You're not necessarily doing the greatest possible good with this limited resources. You're sort of given it to your friends, which is, I think, sort of morally questionable way of distribution. So we had an issue in 2011. We had what I call distributive justice issues in hepatitis C in 2011. So this new medication was approved. This is, again, remember the jump from 50% to 75%. This was the first of this very new class of drugs. Response rates were increased significantly. And of course, this is now 19, not 1922. The pharmaceutical companies that made this, there was warehouses of this stuff ready to go on the day that the FDA approved it. So there was certainly not a production issue in the modern time. But there was a cost. So these medicines are very, very toxic. And it was very time consuming both to get the medicines for patients and to manage them while they were on therapy. So if I was going to see a patient, it would require a lot of clinic visits, a lot of phone calls talking about side effect management, a lot of time. And at the time, from our own experience here at University of Chicago, we had about 500 patients that were waiting for this new drug. And they were calling and they were sort of emailing and wondering when it was going to come out. And when we really sat down as a group, we realized that in addition to all of our other responsibilities, we can only probably safely, each practitioner could probably only safely start about three people per week. And that's really to offer, deliver the care that we wanted to give them to make sure that this is going to be safe. So of course, we have a limitation here. So we have all these people that want therapy. They're calling. They're asking us. And we're not going to be able to treat them all. So how are we going to allocate this resource? So we published on this prior to the medications being released. And we wanted to sort of propose two different models of distribution. We discussed both of them. One of them is, of course, first come, first serve. And this is what I call the deli line, where you just pick a number. So the first people into clinic, they're the ones that get it. We're not going to make any judgments about who they are, what they are. You're just first in line. And this is very simple. And this is what a lot of centers did when these medications came out. And actually, in a way, you're sort of saying, we're offering equal access because first come, first serve. Form a line. And we're not going to make any judgments. So there are some advantages. Of course, our model is going to become very saturated very quickly after the first 20 patients came in the door and the other 480 were waiting. And it does ignore medical need. I mean, you're just counting every patient's medical need exactly the same. It probably doesn't work. So we proposed a needs-based system where we prioritize the sickest patient. We thought that the drugs, when the patients remember that graph that I showed you as you progress to cirrhosis, those are the patients that are most in immediate need of therapy. We were fairly easily able to identify them. We said, these are the folks we should treat first. And that's the system that we set up. The disadvantage is this is very complicated because it takes a lot of time to triage these patients, to contact these patients, to make sure everyone knew where they were going to be in line. So it took a lot of planning. And we ran a risk that the patients who had been calling and waiting and when is the drug going to be there? When is the drug going to be there? And I just saw in the news, the drug is out and we'd say, we've got it, but you got to wait because we're giving it to other people first. And of course, that conversation sometimes went better than others. I'm sure lots of people went elsewhere to find the medication. So here's our system. We proposed and we developed a needs-based allocation system where we divided patients into high priority and low priority. And it actually turned out that by the time everyone was seen, we were able to treat anyone that wanted therapy essentially in the first year. But something very interesting happened. What we realized, as you can see here, I'll orient you that this red bar is patients who are sicker, the advanced fibrosis patients that we treated first. And then the blue bar is the less sick patients. Almost 50% of these patients, we had to stop their therapy because it was so toxic. And they never even got any benefit from the therapy. They were having a lot of adverse events. They required a lot of management and they didn't really benefit. So what do we learn from this first bottleneck is that although treating the sick as first was probably very ethically sound, it may not have been the best medical decision. We probably overestimated clinical trial data of outcomes and underestimated the safety data that we saw. These clinical trials had highly selected patients, very different than the patients we were actually seeing in the real world. And we really, we felt good. We set up a moral framework, but in reality, it didn't really hold up to scientific reality and required a little bit more thought. So going back, so that was sort of what happened in 2011. And I wanna briefly in the time that I have left, talk a little bit about what's going on now. So if you turn on a TV in prime time, you're gonna see people riding horses through the prairie, talking about how their hepatitis C was cured and this very pensive woman deciding she wants to be and she's looking off into the distance about her hep C being cured. So there's obviously a lot of marketing going on right now. This medication was purchased for $11 billion from the company that made this medicine. You can see there's a lot of price tag associated. But I will tell you, it really works and it's really safe and you're curing a lot of people. So everything is great. Here's the rub is the cost. So the cost of this therapy is our second resource limitation. This is our second bottom line. This is data from four different regimens that are very, very highly effective. They're all about the same. They're all extremely well tolerating. You can see on the short end, it's $60,000. That's just for a small group of patients. But on the long end, it's about $300,000 for a course of therapy for a cure. So certainly a large price tag that's associated with it. Economists have looked at this. I'm not an economist so I'll do my best here. And they have shown that compared to previous standard of care and when you take into account the cost of someone decompensating from liver disease or maybe needing a liver transplant and all these things, the incremental cost-effective ratio is less than 100,000, less than 50,000 for a lot of these patients. So it makes sense on an individual basis to treat this patient just from a cost standpoint alone. But remember, we have five million people in the United States that have hepatitis C and we have a safe drug that you conceivably could put every single one of those patients on this drug. So a little simple math and you've got yourself up to $300 billion to treat at these prices. So there's no way as a society that we're going to be able to treat all these patients, let's go back to treating the sick as first. So this is sort of this default that we keep going back to. And that's exactly what's going on right now is we're treating the sick as first and there is some merit, but there's also a lot of concerning issues about this. So this is data, this is a paper that was published just a few weeks ago in the Annals of Eternal Medicine looking at Medicaid restriction policies in the United States. And to orient you, the lighter blue, this is, so most Medicaid policies will only treat if your fibrosis level is at a certain point, meaning you have to have a certain amount of scarring of your liver in order for them to pay. And you can see the lighter blue, the less scarring that you need to have. So if you live in Maine, you barely need any liver disease in order for Medicaid to pay for your hepatitis C medications. Sadly, if you live in Illinois, we have one of the most restrictive policies. You actually already need to have cirrhosis in order to get your medication paid. So forget about preventative medicine, forget about preventing disease. You actually kind of need to be on debt stores in order for your medications to be paid. Everybody else will be denied. And this is problematic. This is not only problematic because this may not be the right system, but this is also problematic because we have a huge disparity around the country. So it depends on where you live, what state you live in and what Medicaid policy you have is how you're going to be treated. There's a lot of heterogeneity here and there's obvious ethical implications of what we're doing as a society by restricting these ways. So once again, you know, we have utility and justice are at odds. You know, are we creating the greatest possible good by treating the sick as patients, but at the same time, is that at the expense of getting medications to everyone and giving them equal access? So the sickest first distribution, what we learned back in 2011 is probably an oversimplification. What about the special populations? What about people that are co-infected with HIV that have a higher chance of progressing to cirrhosis? What about transmission? This ignores the idea that people that are now getting this virus and are not being able to treat are still transmitting the virus and they're still passing it on to other people and you're making your problem much worse. And what about all the healthy patients that we're going to lose the follow-up? So there's lots of patients that, you know, will go to their doctor and say, your doctor will say, you know what, you're too well, you know, your medicaid's not going to pay for you for another 15 years and then the guy says fine and then 20 years later he comes back very, very ill. Those patients, in reality, will get lost over and over again. So we're missing a comprehensive framework. Now, of course, I don't have the answer but I'm proposing some thought that needs to go into this prior to these new medicines coming out and sort of a way to think about this and at least a starting point to begin these discussions. I don't have the $300 billion, but I think there's things we need to think about as these new medicines come out. So when we're thinking about cost, really thinking about what is the cost of the development of these drugs? How are we dealing with pricing? So does pricing need to be regulated and now there's a lot in the news of how much the government needs to be involved, not just state government but on a national level with regulating pricing? What kind of negotiations are going on with industry? I can tell you it's not transparent. We don't know what goes on with industry right now and how different payers will negotiate and get different prices. So there's issues with that. What about the science? They're churning out new and new drugs. We have our liver meeting this weekend and I guarantee you there's gonna be 10 new drugs and new data. Do we really need all those when we can cure almost everybody? Do we really need 11 weeks instead of 12 weeks? Is that worth another $3 billion? I don't know if it is. Real world safety. We kind of got burned in 2011 because clinical trial data was very different than real world data. And then finally the ethical issues. These policies are made in isolation and we're not necessarily thinking of a unified ethical principle, really thinking about justice, really thinking about are we getting the drugs for the patients that need them the most and are we really allowing for equal access or at least the best we can do within this framework that we have. So a few concluding statements that scientific discovery and innovation when they are completely successful are going to have its own set of ethical issues. When science wins and we're probably gonna see this more and more over time we're gonna have these unique types of issues and they're probably gonna be based in resource allocation and resource limitation. Now I'm biased because I treat a lot of hep C and I think a lot about hepatitis C but I think it's even just bigger than these five million people because I think this is a test case. This is our first big time cure. If you think about it, we don't really cure that many diseases and it's coming with a huge, huge price tag. How are we gonna handle this? And I think the reason why this has gotten so much press and so many people are interested in it is because this is gonna show us how are we gonna deal with these things? Hepatitis C was in the news for a long time and there was a pause for two weeks when this drug, this new cholesterol medication came out that cost about $15,000 a year for this new injectable medication that's supposed to work really well. These things are happening and right now our policies are very, very disjointed of how we're really going to handle this so I'm advocating to have really a more thoughtful approach to taking all these things into effect of how we're gonna distribute these curative medications and procedures. So I'll end there and do I have time for questions or? Okay, great. Thank you very much. The Pennsylvania prison system about not treating one particular patient who has a high profile but also a thousand patients that have hepatitis C that have been diagnosed. I've been making the argument that perhaps the question is whether or not they've been evaluated for treatment but could you assess that in the context of your justice paradigm that you're trying to look at? So treatment of hepatitis C in the prison system and how, yeah, so it's funny because again there's two comments I wanna make about that. One is there's very large disparities in the United States based on which prison you go to. People have said sometimes the best way to get your hep C treated is to commit a crime to go to jail for three months. It's not a joke, it's sort of serious because a lot of places actually you can get treated. A lot of this has to do with negotiations that the state has made or whatever prison system has made with the drug companies. The prison population and especially when we're talking about patients that are in prison, we're talking about patients who a lot of intravenous drug users and patients that are at very high risk. Again, these patients should, this is a very highly stigmatized population so I think they, taking it back to the paradigm, these are patients that have very limited access. So I think these are patients when we think about justice and we think about the types of therapies and medications that everybody should get that they are not getting this and it also sort of fulfills this utilitarian because these are probably the patients that need it the most. These are the patients that oftentimes have very advanced liver disease and also sort of as a societal benefit these are patients that have very, very high risk of transmitting it to other patients. So again, your example of prison is a perfect one because this is a reservoir of infection and something where in general we've done a pretty poor job of making sure these people get access to care. Andrew, thank you so much. Thanks. Thanks. Thank you. Our next speaker will be Dr. Stacy Tesla-Lindau, an associate professor of obstetrics and gynecology and medicine and geriatrics at the University of Chicago. Dr. Lindau received her MD degree from Brown University, completed a residency at Northwestern and holds a master's degree in public policy from the University of Chicago. Dr. Lindau's interests are wide-ranging. She investigates female aging and sexuality and urban population health improvement and fairness in healthcare. Dr. Lindau is the director of the program in integrative sexual medicine at the University and also directs a different program, the Southside Health and Vitality Studies for the University. Today, Dr. Lindau will speak to us on the topic of the ethics of sustainability. Join me please in welcoming Stacy Lindau.