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What is the Heart Failure Collaboratory? · Cardio Pod: Heart of the Matter

0:00
Well, welcome to Heart of the Matter Cardiopod.
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I'm Chris O'Connor, cardiologist at the Inova Health System and adjunct professor of medicine
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at Duke University.
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And we're here to really launch an innovative program of a cardiopod focusing on innovation
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in cardiology and cardiology research.
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And today I'm excited that we have a novel concept known as the Heart Failure Collaboratory.
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I'm excited to have the guests that we have today and I'll introduce them.
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They're around the table.
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We have Joanne Lindenfeld, who's a heart failure cardiologist and professor of medicine from
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Vanderbilt University.
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We also have Dr. Scott Solomon, professor of medicine at Harvard Medical School and heart
0:51
failure specialist who is with us today.
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We have Dr. Mitch Sopka, who's the chief of heart failure at the Inova Health System.
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And Dr. Bill Abraham, who is a professor of medicine at Ohio State University, heart failure
1:07
specialist.
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Dr. Mona Fuzot, who is adjunct associate professor of medicine at Duke University and heart failure
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pharmacist.
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And Dr. Peter Carson, who is heart failure specialist near emeritus, Georgetown University,
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professor and and now residing in Rehoboth Beach.
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Welcome to the Heart of the Matter podcast.
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And before we get started, I want to ask each and every one of you to tell us something
1:37
unique about yourself.
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And we'll start with Dr. Fuzot.
1:41
Oh, wow.
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I have to go first.
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I'm going to say I used to live in Los Angeles and I was a drummer and I've actually recorded
1:49
a track with a band in a studio.
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I don't think many people know that.
1:54
Fantastic.
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Well, while we're on music, Scott Solomon.
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Yeah, I thought this was going to be unique.
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But now that Frank Ruziska told everybody at the SC that I was a musician, all 5000
2:07
people in the room, I don't know that it's unique anymore.
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But I am a jazz pianist and I didn't know, Mona, you were a drummer.
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But someday we're going to have to play together.
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So we aspired at some point to get the S3 Gallipers form.
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So Joanne.
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So an interesting thing is that I paid my way through college by being a late night
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DJ.
2:30
Awesome.
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We have a musical team here.
2:33
OK, Bill.
2:34
Well, I have absolutely no musical talent whatsoever.
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I guess.
2:40
Well, what can I tell you?
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I have eight children, including the 10 year old twin girls that just got off the school
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bus.
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With that gone, you're going to be paying tuition to college for a long time.
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Mitch, I will not be retired or a professor emeritus for many years to come.
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Let's see.
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I was in a high school band, but it's not near the performance ability of my colleagues
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here.
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I will say that I have some athletic talent, sort of.
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I was a national champion ultimate Frisbee player.
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And that is how I met my wife.
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And were you on scholarship for that at UVA?
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I can't remember.
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If only a scholarship existed for that.
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Dr. Carson.
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What's he say?
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He will say that I'm the chief of cardiology for Hoboth Beach.
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How's that?
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What about me?
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Well, I aspired to be a lifeguard.
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That was my first job and placed in the Master of Nationals in swimming just a couple of
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years ago.
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And I'm looking to see in my retirement if I can make it back to the lifeguard stance.
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So there you go.
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Well, let's get back to the topic at hand.
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And that is the Heart Failure Collaboratory.
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What is it?
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Why is it an innovative concept?
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Dr. Fousa?
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Sure.
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So the Heart Failure Collaboratory is it formed organically out of a think tank meeting.
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It's a public-private partnership with the FDA and includes a number of different stakeholders.
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We have patients, most importantly.
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A lot of industry members, both drug and device developers and a number of academics, many
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represented here.
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And then we have some NIH and payer participants.
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And then a lot of the FDA is also participating.
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So it's quite a good blend of various stakeholders that participate in clinical trials and really
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came from the concept of stimulating innovation and development in the field of heart failure
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where a lot of other therapeutic areas have received attention from investors and investment.
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We found that they were starting to move away from cardiology because of the nature of our
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trials and the cost.
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And so this really was meant to stimulate interest in continuing to develop therapies
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for patients.
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And really, when you talk about the development, Mitch, and what the Collaboratory can do,
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this process is really broken.
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When you look at how long it takes from discovery of a molecule or device to get it into clinical
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trials, all the phases of clinical trials, get it approved with meaningful endpoints
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and results and trial designs, and then have third party payers accept those results.
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I mean, this ecosystem right now is really challenged.
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Could you comment on that?
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Dr. Mitchel-Kelsey, M.D.
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I mean, I think you described that perfectly, which is there are all these barriers to getting
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a conceptualized idea to a new product that has been tested, has a very high risk of failure
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all the way along, preclinical testing, clinical testing, phase one, phase two, phase three.
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And once you finally can get that very small percentage of new investigational therapeutics,
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either devices or drugs, through that evaluation system, you've generated the evidence, you
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manage to get it through regulatory approval, and then the final barrier is payer approval
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so that patients actually have access to it.
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That is a huge task.
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If you take into account the entire ecosystem of options, millions to hundreds of millions
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of dollars and many, many years to actually get something to patients, the failure rate
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is so huge that the financial and time commitment outlay is massive, such that only very few
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companies can really participate in that system.
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And there's a huge disincentive to really take a ton of risks because of the cost of
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getting something through that process.
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Well, let's jump into that a little bit deeper, Joanne, particularly on the device side.
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And I'll ask Bill Abraham to also comment on device development.
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Have there been any innovations, any movement in this space to make it easier?
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I mean, at one point, almost all devices were being developed overseas and not in this country.
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That seems to have pulled back, but we still have challenges.
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We can get the devices through the clinical trials and it still takes time.
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But then we've got the third parties there too.
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So Joanne, what do you see as the challenges in 2022 for device development?
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The device trials, there are far fewer patients, but they're still very difficult to recruit
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patients because there's a lot of centers that aren't involved in devices.
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And they're often small companies with limited budgets.
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So part of the thing has been the breakthrough designation, which allows us to have devices
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approved for intermediate endpoints and then get out on the market and then develop them
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so that these small companies can anticipate some funding to keep those trials moving on
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to get some results about heart failure, hospitalizations and mortality.
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So it's been very important there.
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And as you said earlier, the number of device trials has gone down.
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These are almost always small companies that then are later bought up by larger companies.
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So I think this has been incredibly important getting everyone involved in that space.
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Bill, what would you say to that?
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Yeah, no, I agree completely with what Joanne has already said.
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I may expand just a bit.
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There are unique challenges to device development, but the climate, the environment for doing
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so in the U.S. has improved.
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The FDA's early feasibility study program encourages first in human and early phase
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studies in the United States.
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So that less and less of this first in human work needs to be done offshore.
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I think that's a positive development.
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Joanne mentions the breakthrough devices pathway for approval, which tries to streamline the
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approval of innovative devices for the treatment of human disease, life threatening and irreversibly
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debilitating disorders like congestive heart failure.
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And so I think FDA is doing its job in trying to bring innovative technologies back to the
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U.S. and streamlining their approval.
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But with all of that said, there are still plenty of barriers, not the least of which
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is just enrollment in the clinical trials that we do.
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And I think that might be said for clinical trials in general, both drug and device trials,
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although there may be different challenges in enrollment in device trials.
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But that process of completing enrollment and follow up in these trials takes much longer
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than it should.
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I think part of the mission of the Heart Failure Collaboratory in developing lean case report
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form, standardized definitions, focusing on underserved populations, the work of the Heart
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Failure Society of America in developing a research network and so on and so forth, are
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all designed to try to move this process along much more quickly than it moves along today.
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And then when we contrast that with drug development, Scott, what are the similarities?
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What are the differences?
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I mean, it still takes a long time.
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I mean, in your career, my career, if you do this in series, we're going to be on the
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beach like Peter Carson pretty soon.
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Yeah, absolutely.
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I mean, look, we have therapies, drugs that have been tested for the last 20 years that
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are still not in the market.
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For example, on the camp to McCarbel, that program started a long time ago.
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I think one of the goals of the Collaboratory and I think a goal that we're actually making
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some headway with is thinking of ways to make this whole process a lot more efficient.
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One of the great things about it is that those of us who are involved in pharmacologic therapies
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are able to hear from people like Joanne and Bill and the companies that are working on
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the device side and the people at the FDA who are thinking about devices so that we
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can start to think a little bit differently than we normally would be thinking about the
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development of new therapeutics.
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And that's been fantastic.
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And I don't think there's any other way that we would have been able to really get people
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together, not just the device and the pharmaceutical people, but also the academics, industry,
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FDA, all in the same room, thinking about the same kinds of problems.
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You also alluded to the fact that once a therapy is available, it's like the tree fell in the
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forest, but was there anyone to hear it?
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We've seen that it can take years and years and years from the time of successful clinical
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trial, FDA approval, even guidelines before we have implementation of the therapies in
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the patients who need them.
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And we've lived that over the last four or five years in the collaboratory, looking at
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what happened with sucupitrile valsartan, for example, which was taken up really quite
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slowly after fairly strong evidence in clinical trials.
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And that's helped us think about what are the other factors that influence how both
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physicians and payers and the very complex group of people, Mona keeps reminding me,
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it's not just the insurance companies, it's the PBMs and so forth that are involved in
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determining who gets what therapies when.
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Lots of challenges.
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I want to ask Peter Carson, who's one of the big impediments, I think, to efficiency
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in clinical trials because he's been at the head of more clinical events committees, probably
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than anybody in the world.
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And these events committees are expensive, they're laborious, they take a long time,
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and he only tries to advocate for the very high endpoints like mortality, which means
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that about 80% of the patients going through these trials don't contribute to the endpoints.
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So Peter, what could you say you would have done differently with your life and with your
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body of work that could have helped the efficiency of trials?
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I think with that preamble, I'm going to have to go to the beach.
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So it's been nice talking to you all.
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But let me just shift this around a little bit.
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I'm going to be a little bit contrarian here, and I'll take you back many, many years to
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a meeting where the upper level Novartis people after Valheft came down and talked about their
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business, if you will, to a group of people that were assembled to discuss the Valheft
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results.
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And the head of the research group went on to describe how many billion dollar drugs
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the company needed to keep going in its current form.
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And this incidentally was, what, 22 years ago, maybe?
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Like the old joke about if you really don't like somebody, you get them a St. Bernard
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puppy for Christmas because then the puppy grows into a giant dog that each had a house
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and home.
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I'm not clear the drug companies, how much they really want to get smaller, particularly
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the larger companies.
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There is an entrenched bureaucracy that exists.
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And I'm not altogether sure how much the FDA wants to get smaller to.
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And as part of that journey that you described, Chris, of doing endpoints and variety of things
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in clinical trials in the grassroots level, I'm always amazed at the things that we are
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required to go and look at.
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And we're all happy to do it.
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That's a way we all go by.
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But I do remember on one of the phone calls with the collaboratory, someone brought up
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the notion of saying, well, the agency is saying they want to move faster and that they're
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more user friendly, et cetera.
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And then industry people said, yes, but when we go and talk to the agency, that's not the
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answer we're getting.
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So higher level on the collaboratory calls, it all sounds very good.
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Then you ask the companies, well, why are we doing all these things?
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They said, well, because the FDA tells us we're supposed to.
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Now we've gone back sometimes to the FDA and said, well, are you really asking for the
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companies to do all these things and document this, document that?
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And the FDA says, well, no, actually we're not.
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They're moving that themselves.
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So where does that come?
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Does that come back to the internal bureaucracy of the companies?
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Does it come back to everyone always likes to blame lawyers?
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So is it the risk management people within companies that then are saying, well, no,
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no, we have to go do these things.
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And the FDA says so.
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And then the FDA, when push says, well, no, we're not.
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But the companies say, well, they tell us they are.
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So to me, the jury is a bit out on how much the really big stakeholders want to move to
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become smaller and more efficient, even though the word is that they should.
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And the story with the small device companies, of course, is they start off small, but then
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they often end up being swallowed up by a big company with a big bureaucracy.
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And that's sometimes the goal, sometimes the way it moves.
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I wish I could feel better about the notion that things would move to a more smaller,
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more efficient system that would move faster.
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I guess I'm waiting to see that happen.
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Wow.
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That's a point of view, Scott, to get to what Peter was saying.
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I mean, this it really can't be true, right?
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That companies want to have they obviously have these big organizations in order to keep
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them going.
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They've got to there's got to be an ROI from all this research investment.
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But they really don't want these 10 year, 12 year timelines of development and then
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10 years of implementation.
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This is way out of bounds for what would make sense from any model that would be beneficial
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to patients.
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Oh, yeah.
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Clearly.
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I mean, they would love to have a two or three year development cycle and then much longer
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time frame.
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But, you know, one of the things that we've been fortunate in the last seven or so years
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of cardiovascular medicine is that we've had some wins and that's been seen by industry.
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And they've seen that, yes, we can do trials that are successful.
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We can come up with new therapies because it had been a while before that.
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And I think that's reinvigorated the field very much.
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And then putting that together with the kind of discussions that we've been having at the
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Heart Failure Collaboratory, particularly in improving efficiency, novel methodology,
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for example, we've spent a lot of time talking about novel statistical approaches to doing
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trials, including trial designs, adaptive designs, things that can make us much more
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efficient potentially and move faster.
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And we get a chance to bounce those ideas off people at the FDA, our colleagues, other
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industry.
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And that, I think, allows us to think about ways to move much faster and much more efficiently.
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I couldn't agree more.
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Now we want to wrap up here and just get sort of final thoughts from everyone.
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Let's go around the room and say, if the Collaboratory could identify a success in a year or two
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or three years, what would that be?
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What would it look like?
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What would success look like, Bill?
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Well, first, I would say that I think that Collaboratory already has a number of successes
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in terms of organizations like this in which I participated over the years.
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I think there have been more deliverables of substance from the Collaboratory than any
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other group that I've worked with.
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The development of lean case report form, standardized definitions, statements about
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the representation of underrepresented minorities and women in trials and so on and so forth,
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very important.
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And in fact, at FDA, at least my experience on the devices side has been that they actively
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promote this output from the Collaboratory, recommending the use of the Hart-Schleier
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Collaboratory Lean Case Report form for Hart-Schleier clinical trials, for example.
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But I think we have to continue to build upon that.
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And ultimately, I think we can track our success in terms of the adoption of these tools and
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the shortening of timelines to regulatory approval on the device side in particular,
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because the technology development cycle and the iteration of technology occurs so quickly
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that quite frankly, the device that you take into a clinical trial today is replaced by
20:13
a next generation device a couple or three years from now.
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So these cycles are very fast and we have to match a development program that lines
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up with that.
20:25
Mitch?
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I would agree completely with Bill, but I want to shoot for the moonshot here of what
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the Collaboratory can accomplish.
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And I think that is with the payers.
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And I think that if we could get the payers to collaborate on the process that we are
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describing where we have all other stakeholders providing input on how to create and design
20:46
development programs and clinical trials to generate evidence that then leads to regulatory
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approval.
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If at the same time we were generating evidence that would lead to payer approval and utilization
20:55
and patient access at a reasonable cost and a reasonable tier of payment and coverage,
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I think that is where we know that we have truly been a success.
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But I think, as I said, I think that is a moonshot and I think that will be our goal
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for many years to come.
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But I think we've made great progress because the payers are involved and engaged and now
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we just need to figure out how to take it forward.
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Peter, what say you?
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If timelines are able to change and the amount of material that is brought in is streamlined
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with the concept of a lean CRF, that's one move.
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But I really like what Mitch said that bringing the payers into the game.
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So this ends up being a process that does not end up being disjointed between approvals
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and then payers paying for the way things are reimbursed.
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Perhaps the Sucubus and stories, one of those, a good example of that.
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If we can move that all in the same direction, that would be really a tremendous advance
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forward.
22:02
Joanne?
22:03
I agree with all those things.
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There have already been a lot of successes.
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Another one, the Hartford Collaboratory is very quick to respond.
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The COVID recommendations was talking about statistics involved in clinical trials and
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what should we do with these clinical trials that are ongoing right now?
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We have to make decisions.
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It was an important one.
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I think also we're going to be able to have a pretty big impact in diversity, both in
22:24
more diverse patients and more diverse investigators, I think because we have everybody together.
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But I would say, I agree with Mitch, but I would think the real moonshot would be with
22:32
all these people together.
22:33
If we could develop a research infrastructure within the United States that was something
22:38
like the cancer folks have, where people could be supported in this endeavor and that people
22:44
could be paid for their work in clinical trials and that payers would pay into this, but Medicare
22:48
potentially too, would to me form a really incredible structure in which to do clinical
22:54
trials rapidly in the United States.
22:56
Fantastic.
22:57
Scott, can you top that?
22:59
Well, I can't top it, but I'm going to add to it and bring up something that we haven't
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talked about today, which I think is also one of the great gems of the Collaboratory,
23:08
which is that we've included a lot of junior people who are early in their training.
23:16
And remember, clinical trials is the kind of thing that you can't really learn unless
23:21
you do them and unless you're part of them.
23:24
I'm really proud that we've brought in a lot of junior investigators who've done amazing
23:29
work and Mitch, you used to be one, but you're not anymore.
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But it's just been really fabulous to see that they have been able to contribute as
23:39
much as some of the senior people.
23:42
And I think that if we have a legacy, it will be to train the next generation of clinical
23:47
trials.
23:48
Really well stated.
23:49
Mona, you get the last word.
23:51
All right.
23:52
Yeah.
23:53
I think the points that everyone made are exactly spot on.
23:58
You know, we started the first meeting through a think tank about learning from our colleagues
24:04
and oncology was one of those that we stressed.
24:07
And so if you think about that, their success in getting patients in trials, efficiency
24:14
of development, how quickly they have been able to move their field and actually have
24:19
an impact on mortality.
24:21
I think that's what we really are aiming to do and get those patients new therapies faster
24:29
and also keeping the companies engaged in developing products for heart failure.
24:34
So we're not turning to something that could turn a profit much quicker, but taking just
24:40
a few days off of development time has huge investment benefits.
24:46
So I think all of those things combined are really important and then as others have mentioned,
24:53
we have had a focus on diversity, both including diverse patients in our trials and training
24:59
the next generation of diverse investigators to attract diverse patients into trials is
25:04
another area we can save for the next podcast.
25:08
Well, this has been a terrific conversation.
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Thank you so much for joining us today and talking about the Heart Failure Collaboratory,
25:16
how we can make the development process better for our patients.
25:21
And we're looking forward to continuing this conversation.
25:24
It doesn't end today.
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And our next podcast for the Heart of the Matter will be discussing statistical concepts.
25:33
So we're going to have to make this, that one very conversational.
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And so brush up on your math and we'll see you in a couple of weeks.
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Thank you very much.
25:41
Good day.