Transcript of BioCentury This Week TV Episode 198
Dr. Joel Kupersmith, former Head of Medical Research, Veterans Health Administration
Dr. Richard Elion, Clinical Research Director, Whitman-Walker Health
Tom Myers, Chief of Public Affairs and General Counsel, AIDS Healthcare Foundation
PRODUCTS, COMPANIES, INSTITUTIONS AND PEOPLE MENTIONED
Centers for Disease Control
Food and Drug Administration
Department of Defense
The New York Times
Steve Usdin, Senior Editor
STEVE USDIN: This week we'll dive into two controversies at the intersection of health, politics, and policy. Will a CDC recommendation ramp up use of Truvada, an AIDS treatment for prevention, and are the benefits worth the risks and the cost? And will responses to the VA health scandal help or hurt the agency's research mission and the veterans who depend on it?
I'm Steve Usdin. Welcome to BioCentury This Week.
NARRATOR: Connecting patients, scientists, innovators, and policymakers to the future of medicine. BioCentury This Week.
STEVE USDIN: New CDC guidelines recommend the use of Truvada, an AIDS treatment, to prevent HIV infection. The guidelines could apply to hundreds of thousands of Americans at high risk of HIV. The idea is controversial. AIDS advocates argued for and against Truvada's prophylaxis on BioCentury This Week in 2012.
OWEN RYAN: And so what we've seen in PrEP is an intervention that has the potential to change the dynamic there -- to move us in a direction where we can start moving away from 50,000 new infections and bend the disease curve so that we're getting the real public-health impact we're looking for.
TOM MYERS: The problem is for this thing to have any preventive effect, people are going to have to take this daily. That's simply not going to happen.
STEVE USDIN: For both sides of the Truvada PrEP debate, I'm joined by Tom Myers, General Counsel for the AIDS Healthcare Foundation, which strongly opposes Truvada's PrEP, and by Dr. Richard Elion, Clinical Director of the Whitman-Walker Clinic, the largest AIDS healthcare provider in Washington, DC.
Tom I'm want to start with you. In 2012, you were on the show, before the FDA had an advisory committee meeting about Truvada's PrEP, and you were strongly against it. Since then, it's been approved, the CDC recommendations have come out -- have your views changed?
TOM MYERS: Not really. The concerns that we had two years ago are the same concerns now. And the evidence is only been a little bit stronger -- has gotten stronger in those two years. The main concern is adherence. This is something that's been approved to take every day. If you don't take it every day, it's unclear you get the benefits of it.
And in the study after study that has been done with this drug, the majority of the people in the studies have not taken it every day. They failed to adhere. In the big study, iPrEx, 46% of all the people in the study had no detectable level of the drug at all, and only about 20% were found to potentially take it every day. And there's all sorts of problems that can occur if you don't take it every day.
STEVE USDIN: So Dr. Elion, in the real world, what you're seeing -- are people taking it every day? Is it working?
DR. RICHARD ELION: Well, as the Director of Clinical Research, I'm involved in a clinical study looking at the PrEP Demo project, which is a demonstration project to see in the real world -- in real life -- how often do people take their medications? And this is occurring in the United States. The studies that Tom has talked about have been predominately in sites outside of the US and not before we understood what Truvada did and whether it worked or not.
Currently, we reported on data recently at a meeting in June where we showed that over 70% of the patients in our study were taking greater than four doses a week. So the idea about adherence being critically important -- absolutely. It's critically important. But I think we're also starting to assemble new data -- as the CDC recommendations have gone along in time, we have new data that shows us that over 70% -- 72% -- took at least four doses a week. It's thought that greater than four doses a week provide effective protection.
So I think the issue about adherence is really changing. I think as the community that's at risk for this starts to understand the risks and benefits of this medication, they're able to participate in a more meaningful way.
STEVE USDIN: And you said, the community at risk -- who do you think should be using Truvada? And then I want Tom's response about what you think about that. Who should or who shouldn't be using it?
DR. RICHARD ELION: Well, I think the CDC guidelines gave us a pretty clear indication of who should be using it. So it's people who are at high risk who are having unsafe behaviors or are at risk of exposure even though they're trying to do safer behaviors. What we see is that what Truvada really offers is an additional tool. We don't want to take away from the message of using condoms and doing safe behaviors, but one of things we've noted that in our study, the people who entered -- 82% were already doing unsafe behaviors.
STEVE USDIN: So Tom, that's one of the things that you wrote up before also, and I'm wondering if you still think it's a concern that we risk compensations, as it's called. People will feel that they're protected, so they won't take these other steps that they should to protect themselves.
TOM MYERS: Right. I think that's still a concern. That's just human nature. In every area of life where people think they are protected, they engage in riskier behavior. And there's no reason to think that won't occur here.
And that's the concern. If you're not taking it every day, it's unclear whether you're getting the protection. If you engage in riskier behavior while you're not getting the protection, your chances of infection potentially go up. So AHF's position has always been if a doctor and a patient get together and, between the two of them, decide that this is something that might work for them, that's fine.
But on a large-scale public-health level, the sort of interventions that were in the studies in terms of being paid to participate in the study -- to take the pill -- free access to the drugs, free medical checkups, free risk-reduction counseling, including free condoms -- all those things don't exist in the real world.
STEVE USDIN: So in the real world, Dr. Elion's saying he's getting 72% adherence. Is that good enough?
TOM MYERS: Well, I won't put words in the doctor's mouth. It's a study, and it's 72% taking at least four days a week. So again, the FDA guidelines are every day. So again, there are still potentially large-scale problems with it. On an individual level, people may be able to succeed on it. And AHF has never tried to get in the middle of a doctor-patient relationship. But on a large-scale public health perspective, most people are not going to succeed on this, and the potential for both new infections, drug resistance, as well as other STD infections is a concern to AHF.
STEVE USDIN: Are you seeing any of those things?
DR. RICHARD ELION: Well, Steve, I appreciate Tom's point of view, but I wanted to make a distinction between the concern about public health based on attitude and the concern about public health based on facts. I believe the AIDS Healthcare Foundation has done a lot of fear mongering around the use of PrEP, and I think it's been a detriment to the community of people at risk for HIV. Let me get to the facts on what Tom said.
In terms of risk compensation -- the idea that people are going to do more unsafe behaviors -- in iPrEx, you did not see any increase in STDs. We don't use the incidence of condom use, which is a self-reported measure, because we don't really believe that there's a lot of trust in that. But we do know that if people are not using condoms, they're more likely to have STDs, and we didn't see any increase in STDs.
STEVE USDIN: Information about pre-exposure prophylaxis, PrEP, is available on the CDC's website. Here's the address.
NARRATOR: You're watching BioCentury This Week.
STEVE USDIN: We're discussing treatment with Truvada as a tool for preventing HIV with Tom Myers and Richard Elion. Tom, I want to give you a chance to respond quickly to what Dr. Elion said there. Fear mongering. Is that what you're doing?
TOM MYERS: No. Again, there are numerous facts to this debate. People are entitled to their facts. In terms of risk compensation, which is what we're talking about here, the iPrEx study that the doctor referred to, those participants had monthly risk reduction counseling. Access to free condoms. These are things that don't happen in the real world. And so to say that there's been no findings of risk reduction or miscompensation, the iPrEx study just elides the fact that they had additional counseling on safe-sex practices.
STEVE USDIN: And there's something else I want to bring up, which is the stigmatization in the gay community of people who take Truvada. Can you explain why that is, and what you think about?
TOM MYERS: No, I cannot. Again, AHF's position has been that, on a large scale, public-health basis, the majority of the people who try PrEP will not succeed on it. And the potential for risk compensation, infections, and another -- STD infections -- is large. And that's why we have concerns about it.
RICHARD ELION: And there's a study already completed in the United States. Let's just stick with the studies in the States, for now. Because the cultural impacts of clinical research and clinical settings are different. In the United States, in the early study, showed a 92% efficacy in the MSM community. In our study, we've got over 72% percent having greater than four doses a week. This is no longer supposition.
The idea that we can traffic in offering opinions about PrEP, when there's facts that show us what the utilization is. And finally, the idea that patients don't have access to free condoms, free condoms and counseling -- at our site, where we take care of over 3,000 indigent and broad variety of HIV infected men and women in Washington, DC, all of that is currently available. I know that many of the sites in the AIDS Healthcare Foundation are for the same kind of counseling and support.
The point is that PrEP is intended to be part of the package of prevention, not the sole piece of the prevention. And these things are already offered for many patients.
STEVE USDIN: So just to -- here. The numbers of patients who are actually taking advantage of Truvada, PrEP are really small. Do you expect that that's going to ramp up as a result of the CDC? Because the way it is now, it's not going to make a big difference from a public-health standpoint.
RICHARD ELION: I think the CDC recommendations have done a lot. I mean I can tell you that the amount of times I've been talking publicly about PrEP since the CDC recommendation, compared to the FDA, is almost a 10 to 1 ratio. So there's way more publicity about this. I think that there's been a lot more efforts to the providers getting educated, the consumers. People at risk are getting educated. And I think we'll see more buy-in.
I don't think the intent is that we think this is for everybody, though. There are clear groups of populations with the certain risk behaviors that this is for. And that's who it's intended for, not the broad population.
STEVE USDIN: I cut you off there, Tom. What did you want to say?
TOM MYERS: Well, first, going back to the study that I keep referring to, the iPrEx study -- that is the primary study on which the FDA approval was based --that occurred, in part, in the United States. So again, we are talking about --
RICHARD ELION: It was less than 10% in the United States.
TOM MYERS: We're still talking about something that happened in the United States.
RICHARD ELION: 90% outside.
TOM MYERS: There you go.
STEVE USDIN: OK. So let's move on, I think, to another issue, which is --
TOM MYERS: I'm sorry. I apologize. And to the extent that these services are available in DC and AHF's clinics around the country, that's true. That's not everywhere. That's not the majority of places. The majority of HIV is trending in the South, in communities of color. Those are areas that do not necessarily have access to these types of services.
And that's, again, it's the broad thing. There might be many people in Washington DC this is effective for, there may be many people that it's not. The problem is we're talking large scale.
STEVE USDIN: Tom, when we were talking in 2012 about this, one of the issues that you raise was the cost to society. And you question whether the cost of Truvada's PrEP was worth it, compared to other ways that public-health money could be spent. What do you think now?
TOM MYERS: Again, that hasn't changed. A year's worth of Truvada is about $13,000 or $14,000. To prevent one new infection via PrEP, you'd have to have at least 45 people taking PrEP and adhering to it every day, to get that benefit.
For the same amount of money, you could treat 20 people with HIV and, again, render them non-infectious. And that's how you prevent new infections.
STEVE USDIN: Is it a zero sum game? Is it one or the other?
TOM MYERS: It's not a zero sum game. It's not one or the other. But if you're talking about where you're going to have the biggest benefit, and how you're going to solve this on a society-wide level -- not an individual basis, but on a society wide level -- that's where you need to put your resources.
STEVE USDIN: Dr. Elion, quickly your response on that. And then the other issue is, are your patients you're prescribing Truvada's PrEP for able to get coverage from their insurance companies to pay for it?
RICHARD ELION: Well first of all, Tom's analogy about efficacy and about the number needed to treat to prevent new cases, I would not agree with at all. I don't want to get into the numbers, but I think that's a gross overstatement and not accurate. I think that the number of cases you can avert and the number of resistance that you can prevent by doing PrEP -- it's been shown in modeling studies, where there's at least a marginal amount of incidents, less than 1%, to be greatly effective.
In terms of getting compensation -- reimbursement, rather -- we've not had an issue for patients. We've been able to get patients who are -- 60% or 65% of patients that we see are on some sort of government-sponsored Medicaid. Usually Medicaid. And so Medicaid has covered Truvada for PrEP, because it's been shown to be cost effective for the amount of HIV in this community, in Washington DC. It's effective and it's a cost effective intervention.
STEVE USDIN: So Tom, is your organization lobbying against the use of government money to get PrEP to prevent AIDS?
TOM MYERS: No. No. Again, what happens with respect to Medicaid, covering it -- it may cover it in Washington DC. There are many, many states where it doesn't cover it. There are many, many states that have not accepted healthcare reform, and they're not doing Medicaid expansion.
So again, what may work in DC, may not work in the country as a whole. And what AHF is focused on is ending this thing across the country.
STEVE USDIN: Dr. Elion, cost effectiveness of Truvada?
RICHARD ELION: The New York Times' article on PrEP displayed the cost effectiveness of statins compared to Truvada for PrEP. Truvada for PrEP was much more cost effective than statins. We're seeing statins covered for heart disease, the analogy is equally strong, if not stronger, for PrEP.
STEVE USDIN: So talking about the big picture, the thing that's really disheartening, if you look at it in the United States now, is we still have large numbers of people who are getting infected with HIV every year. Every week, every day, it's happening.
Truvada as PrEP, if you believe it or you don't believe in it, it's not going to solve a problem, is it?
RICHARD ELION: No. There are 50,000 cases, almost an infection every ten minutes. And globally, there's two new cases for every one patient started on treatment. So this is not going to solve the epidemic. It needs a group kind of intervention.
The first is for people to get tested, know their status. One of the key issues among the MSM community and the adolescent community is that, much higher groups of that population are not aware of their HIV status. So it's important for people to learn about that. Two, to then get those people who are positive onto treatment. The treatment is prevention, I'm sure that Tom and I both agree on that principle. That treatment is prevention is an incredibly effective way to decrease spread.
Where PrEP fits in, in my opinion, is for the gaps in that transmission cascade.
STEVE USDIN: So Tom, tell me. There is some area of overlapping agreement between you two here. We have about 30 seconds left. What do you think needs to happen to make a big dent in the public-health problem?
TOM MYERS: To make a big dent, as the doctor said, treatment is prevention. We need to find the people who have it, don't know it. Link them to care, get them retained in care, get them adhering to medication.
We talk about the various percentage of effectiveness of PrEP. We know that people who have HIV, are compliant with their meds, have their viral load suppressed, are 100% non-infectious. And since you can only get HIV from someone who has HIV, you can render that person non-infectious. That's how you're going to end this epidemic.
RICHARD ELION: But we also know that in communities that have been effective at that, like Vancouver and San Francisco, the decline in cases plateaus. And even though you're doing optimization of all those tools, there's still a group. And it's for those people, if we can find another way to help, is where we're trying to go.
STEVE USDIN: That's all the time we've got for this discussion. Hopefully we'll have both of you back and talk about this in the future. Next, the former head of medical research at the Veterans Administration, and what the VA scandal could mean for medical research. First, a snapshot of the VA health system.
NARRATOR: Now, back to BioCentury This Week.
STEVE USDIN: To discuss today's problems with the VA health system and their implications for the future, I'm pleased to welcome Dr. Joel Kupersmith back to BioCentury. Dr. Kupersmith directed the VA medical research program for eight years. Dr. Kupersmith, I want to get on to the research mission a little bit later in our conversation, but to start with, what's your analysis of what's caused the waiting list problems and what the solution is?
DR. JOEL KUPERSMITH: Well, it brought together everything, every problem that the VA has. And as I said in writing about it, the underside of the VA came out. There are governance problems. There are problems with oversight and auditing, verification of numbers.
And they set up a standard that was impossible to keep. It is not necessary for every patient to be seen in two weeks. And what happens is you just can't do it. So people tend to at least do gaming, if not outright fraud, which actually surprised me. I didn't think that would happen.
But there's always been a lot of gaming with numbers. And there weren't enough doctors for the clinics. There wasn't enough clinic time. There was a lot of pressure on it. Rewards and punishments were based on these numbers.
So all those things coming together brought on what happened, which was a major disaster.
STEVE USDIN: So there have been books written about the VA medical system as an exemplar for the world in the debate over the Affordable Care Act. It was held up as an example of why there should be a single-payer system. Ultimately, that didn't happen, but there still was that perception out there. Was that all wrong? Was that all based on fantasy?
DR. JOEL KUPERSMITH: Well, I think the underside of the VA and the problems with the VA were not sufficiently explored in those things. And the VA was a pioneer in many of the things that are happening in healthcare reform. It was a pioneer in performance measures. And yet, the performance measures that evolved were diffuse and overly complex.
It was a pioneer in the electronic health record, which is crucial to modern healthcare and crucial to healthcare reform. But the electronic health record of the VA as it is now is way behind. It's not web-based, for example. And they're working on a new one.
So I think, particularly in the mid-1990s, it advanced tremendously. And many of the advances in the VA came then. But since then, and especially in the past several years, it's flattened. And they have not progressed the way they should.
And in a way, also, they have not focused on basics. They need basic auditing, basic oversight, basic governance principles. And these have not necessarily been applied in the VA.
STEVE USDIN: So one of the other things that the VA system pioneered, particularly under your watch, was medical research and using the capabilities that it had that no other medical system, in the US at least, has. What can you say about where that is and what might happen to the future of that research mission as a result of the current problems?
DR. JOEL KUPERSMITH: Well, I think VA research is actually in very good shape mainly because it has wonderful researchers. And it also pioneered in health-services research and evaluating systems. For a long time, it's been a leader.
I ran the VA research program for eight years, and that started nine years ago, and it was having a bit of difficulty then which we had to address. It was smaller, so it was perhaps easier to address than the system as a whole.
But I think the two main issues coming up, whatever is done in the VA, and particularly there's going to have to be outsourcing now, is going to be expensive. And whether that's going to effect the VA research budget or not is not clear. I hope it doesn't. It's not a very large part of the VA budget, so it shouldn't. But it may.
The other is that if you have significant outsourcing, you lose track of the patients.
STEVE USDIN: That's exactly what I want to talk to you about right when we come back. We'll be right back with Dr. Joel Kupersmith.
NARRATOR: Every month, BioCentury This Week will feature Profiles in Innovation, a special segment highlighting the stories of innovators whose work is improving lives and transforming the world of healthcare.
STEVE USDIN: We're back with Dr. Joel Kupersmith talking about the VA health system. So Dr. Kupersmith, you were talking about the concerns that people are going to go outside the system. So one of the things that's been proposed and is probably going to happen to alleviate the problems of the VA is to allow patients to go to the private sector to get care. What does that do to the research that the VA's been able to do by being able to track people over long periods of time?
DR. JOEL KUPERSMITH: Well, it's going to be an issue and a problem. First of all, a lot of the VA care now, a lot of care of patients who are enrolled in the veteran system goes outside. Actually almost 90% have some kind of outside insurance. So there is a proportion that goes outside, and many of the VA databases take that into account.
For instance, the diabetes database has Medicare data in it, at least Medicare administrative data. So that's one point. Another point is that now we've kind of learned a lot about how to keep security. And that's a big issue for the VA.
And I think one of the things that has to be done is there has to be a lot more collaboration in databases, a lot more data sharing. And a good vehicle for that is the distributed database where each entity keeps its own data but then contributes what it needs for particular studies. And I think that's really the way to go.
STEVE USDIN: And I want to make this more concrete for people who are watching and what we're talking about. What are some of the examples of the things the VA system has been able to do because it has this ability to track patients, many patients, over time?
DR. JOEL KUPERSMITH: Well, for example, in diabetes, it can do quality over time rather than as individual points in time. So you can look at trends in diabetes patients and see what the totality of their care is. And there was a study in suicide looking at some of the precursors of suicide because we could look back in the electronic health record.
We have databases -- I say we. I'm not at the VA anymore -- but there are databases for heart failure. We can trend heart failure over time, look at most cost-effective ways of treating it. They were databases related to cardiac catheterization, which could look at many factors related to that.
So there are a lot of good research that's come out of that. And again, the VA has been really a pioneer in it. The other thing that VA has been a pioneer in is clinical trials. And some of the major clinical trials recently in prostate and cardiac surgery and many other areas have been done in the VA.
So that's another area where if there are less patients, it can be difficult. But again, partnering. VA partners with NIH in many of the really good large studies. So it just has to get more partnering, more patients from the outside. And that's really the way to go. But the VA, because of its firewall, because it's of a government entity, it's going to have to learn how to share. And that's really the big issue for it.
STEVE USDIN: And looking forward then, what's your feeling about what it could be? What's kind of the next step if we get over this hump and the VA goes forward, what's some of the low-hanging fruit for positive things that could come out of the research mission of the VA?
DR. JOEL KUPERSMITH: Well, I think there are many topics for clinical trials that could be done in many areas. I think the areas -- there are some major studies that are going to be ongoing -- collaborating with DOD which is actually unique. That was the first time that happened when we did that.
And in PTSD and TBI, and in looking for, for example, biomarkers for both of those conditions, very important. If we can predict who will get it, if we can make predictions, either genetic biomarkers or others, treatments, I think drug treatment of PTSD would be a good topic for research in the VA. We actually started some discussions about that. Same for TBI.
There is really no good long-term drug treatment for it, and it would be difficult to find one. But I think that's another area. And then suicide, I think research on suicide would be very important. That's such a big issue on returning veterans.
STEVE USDIN: And then you talked about collaboration. Is it you're talking about collaboration with NIH or the other institutions? We have to bring more people into this discussion.
DR. JOEL KUPERSMITH: Well, I think on the clinical trials, collaboration with NIH is the most fruitful. But on the databases, there are other large health systems, Kaiser and others, that can be discussed, academic medical centers, for follow-up of patients. That's where the collaboration should be.
STEVE USDIN: Well, thanks very much, Dr. Kupersmith. That's this week's show. I'd like to thank my guests, Tom Myers, Richard Elion and Joel Kupersmith. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #BioCenturyTV. I'm Steve Usdin. Thanks for watching.