Latest / Cardio Pod: Heart of the Matter / Diversity in Heart Failure Clinical Trials

Transcript

Diversity in Heart Failure Clinical Trials · Cardio Pod: Heart of the Matter

0:00
Good day everyone.
0:06
I'm Chris O'Connor and this is Heart of the Matter podcast of the Heart Failure Collaboratory.
0:11
And we're here today to discuss diversity in heart failure clinical trials.
0:15
And I'm very pleased to have an outstanding faculty with us today.
0:19
I'll go around the room and ask you to introduce yourselves.
0:22
Back again by popular demand, Dr. Joanne Lindenfeld.
0:25
Hi.
0:26
I'm a heart failure and transplant cardiologist at Vanderbilt University.
0:30
Dr. Vanessa Blumer.
0:31
Hi.
0:32
It is such a pleasure to be here.
0:33
I am Vanessa Blumer and I am an advanced heart failure and transplant cardiology fellow at
0:38
the Cleveland Clinic.
0:39
Thank you.
0:40
Dr. Melvin Eccles.
0:41
Hello.
0:42
I'm Melvin Eccles.
0:43
I'm actually a general heart failure doc, also the chief diversity equity inclusion
0:48
office for the American College of Cardiology.
0:50
Thank you, Melvin.
0:51
And just for our viewers, Melvin is not in San Francisco.
0:54
He's in Atlanta.
0:55
Dr. Nathreen Ibrahim.
0:57
Hi, everyone.
0:58
I'm a heart failure and transplant cardiologist and I'm one of the Commonwealth Fund Fellows
1:01
in Minority Health Policy at Harvard.
1:03
Dr. Mitch Sapka.
1:04
I'm Mitch Sapka.
1:05
I'm the section chief of heart failure and transplant at Nova Heart and Vastinolence
1:08
in Paulist Church, Virginia.
1:10
And Dr. Wayne Batchelor.
1:11
I'm Dr. Wayne Batchelor.
1:12
I'm the director of interventional cardiology and interventional research and innovation
1:16
at the Nova Heart and Vastinol Institute.
1:18
Thank you, everyone.
1:19
And we're really going to tackle the three topics, diversity in clinical trials, the
1:25
landscape today, what we can do to do better, and are there any specific incentives that
1:31
might enhance a more representative population in our heart failure trials.
1:36
We've done well in developing therapeutics and devices in clinical heart failure, but
1:41
where we've really not made as much progress as we've liked to is the representation of
1:46
the population, the patients, the citizens who enter these trials.
1:51
And that really gives us a difficult time in providing meaningful conclusions in the
1:57
special populations, underrepresented minorities, women, the very elderly, and other populations.
2:03
So I'm going to start with Dr. Lindenfeld and just say, Joanne, as you look at the landscape
2:08
of device and drug trials, what have been the challenges?
2:12
Why can't we have a more representative population?
2:15
Chris, I think there's a number of reasons.
2:18
I think probably one that we're trying to evaluate more carefully is that many of the
2:23
centers that participate in clinical trials are not in areas that recruit quite as diverse
2:27
of a population as what we would see across the general United States.
2:31
So I think that's an important issue.
2:33
And then I think a second pretty important issue the Heart Failure Collaboratory has
2:37
addressed is that to really recruit diverse populations that you've described, the investigators
2:42
probably need to at least to a greater degree than they do now represent the diverse populations
2:47
that we're trying to enroll.
2:48
So we know that if we have more women PIs, we have more women in trials.
2:52
If we have more black PIs, we have more than trials.
2:55
So I think really trying to encourage participation of those diverse groups in the clinical trial
3:00
leadership is going to be important.
3:02
Excellent, Joanne.
3:03
And I'm going to follow that up with Dr. Echols.
3:05
Melvin, when we recruited you to faculty at Duke University, you became part of our Duke
3:11
Community Network and built a practice in Lumberton, North Carolina, one of the most
3:15
diverse communities in the country.
3:18
Describe how you set up site-based research and the opportunities and challenges that
3:23
you faced in recruiting representative populations in clinical heart failure trials.
3:28
So I think that I completely agree with Joanne.
3:31
And I would also say that oftentimes clinical trial diversity is more of an afterthought.
3:37
So after the protocol has been designed, after everybody's figured out what they want to
3:40
do, and really you should think about it at the very beginning.
3:44
So whenever I started in Lumberton, which I have to say, because this is one of the
3:48
most diverse counties I've ever seen.
3:50
So Robeson County had a third percent African American, a third percent Native American,
3:55
and then a third percent are white.
3:56
And so it was really diverse, the Lumbee tribe in North Carolina and very closely tied family.
4:02
And so really the first thing that we had to do was just get ahead and be good doctors
4:07
to them.
4:08
I think that the more you actually are in the community and people know who you are,
4:12
the more likely they are going to want to hear what you have to say.
4:15
I was very blessed to have Dr. O'Connor at the helm whenever I first started to help
4:21
me push forward the initiatives in the community.
4:23
And then you have to have really community and the hospitals there.
4:27
They have to want clinical trial research in the area.
4:30
In doing that, we actually had a large heart failure population.
4:33
My patient panel was 2,500 and it was a wide range of heart failure.
4:37
And so I think just in general, they have to go where the patients are.
4:41
And then you also have to make sure that you are a part of the community.
4:44
And not just dropping in for a particular purpose.
4:47
Melvin, you did a terrific job there.
4:49
Now the only problem is that we need you to go to about 15, 20 other communities through
4:55
the country.
4:56
So we're lining you up for various employment opportunities throughout the country so you
5:00
can do what you did in Lumberton, which was really special.
5:03
One more thing, there is the community-based participatory research model.
5:07
I do think that we need to focus a little bit more with the community in terms of bringing
5:12
clinical trials as an overall process.
5:14
And not just one specific trial.
5:16
The communities themselves have to understand the purpose of clinical trial research and
5:21
be a partner with you as you roll out these trials.
5:24
That's incredibly important.
5:25
And so I think as we think about how do we reach areas such as the one I was in, I think
5:30
looking at it as a community-based participatory sort of situation is probably the way to go.
5:35
And Dr. Batchelor, you've thought about this a lot and not necessarily in the heart filler
5:39
trials but in interventional trials and did some great work around the Platinum Diversity
5:45
Registry and Database.
5:48
Tell us specifically why we've underperformed in recruiting underrepresented minorities
5:53
in clinical trials and what you've identified as a potential solution.
5:58
Thanks Chris for allowing me to participate in this interesting webinar.
6:01
So several of the speakers have already commented on some of the issues related to representation
6:06
within the clinical trial leadership.
6:08
I think that this is really important.
6:10
Dr. Lindenfeld has nicely stated the importance of this.
6:13
I think until we get very good representation across all aspects of clinical trial leadership
6:18
on steering committees, DSMBs, et cetera, we'll continue to struggle with representation
6:24
in terms of patient enrollment.
6:25
So very important point.
6:27
Number two, Dr. Echols mentioned the importance of sites.
6:31
How we select the sites, perform and enroll in clinical trials is critical to the diversification
6:37
of clinical trial in general.
6:38
The demographics of patients will generally follow the geographic location of the sites.
6:44
So we've got to do a good job of being intentional about our site selection to ensure that the
6:50
diversity of the patients is represented through site selection.
6:54
Historically, we've tended to go to sites that have performed well in research and have
6:58
been previously identified by sponsors and academic thought leaders.
7:02
We've got to think a little bit outside the box by looking at new sites or training new
7:06
sites and developing existing sites to enroll better when they have good diversity.
7:12
There are some other impediments to enrollment that relate more to patient issues.
7:16
There is still a lot of mistrust of research, particularly in underserved communities such
7:21
as minorities.
7:22
We've got to dispel these myths.
7:23
We've got to do a good job of educating the populace as to the importance of clinical
7:27
research and how it's conducted and that it's done in a manner that protects patient safety.
7:33
I think we've got to do a better job of reaching out to the communities and making them understand
7:37
more about the importance of research and how it can impact their families, their future
7:42
kids and grandkids in terms of coming up with device and pharmaceutical data that's most
7:46
important and relevant to them.
7:49
And then finally, I wanted to say that the pathway to diversity runs squarely through
7:53
the United States.
7:54
It's been shown that studies that enroll patients outside of the United States are far less
7:59
diverse.
8:00
But the United States actually does a better job in most countries at enrolling both African
8:05
American or Black patients and Hispanic patients and other patients as well.
8:10
So if we don't get this right, the rest of the world, unfortunately, will fall behind.
8:15
And given that the clinical trial database is now global, we've got to make sure that
8:19
our US patients are well represented in studies that are global.
8:22
Those are just some bots and I'm sure that others on the panel will have some other ideas
8:26
as well.
8:27
Thank you, Wayne.
8:28
A lot has to be done in the planning phase to get this right.
8:31
And you outlined really three or four important issues.
8:35
The US has to be involved to a greater extent in the recruitment.
8:39
The site selection is extremely important and representation on the committees and leadership
8:44
are very important.
8:45
I want to ask Dr. Blumer to comment on the recruitment of women and Hispanic patients
8:51
into clinical trials, something that I know you're passionate about.
8:54
What are the unique challenges of those particular patients in heart failure trials?
9:00
Thank you so much, Dr. O'Connor, for that important question.
9:02
I'm indeed very interested in this topic and particularly interested in the sleeping enrollment
9:07
of women and Hispanic patients in clinical trials.
9:10
When it comes to women, there are many barriers that have been described.
9:13
I think study burning is an important one.
9:17
So pragmatic trials could definitely facilitate recruitment, distrust of researchers and lack
9:23
of understanding of the clinical process.
9:26
Also sometimes influences decision making.
9:29
Now specific to Hispanic individuals, there are many barriers to enrollment that are common
9:33
to other underrepresented groups, but they also have the unique barrier of language and
9:37
sometimes a cultural barrier as well.
9:39
In all, I think it comes down to the brilliant point that Dr. Lindenfeld made earlier to
9:44
overcome women-related barriers and increase women recruitment in clinical trials.
9:50
You need more women leading clinical trials and to increase Hispanic individuals, you
9:55
need more Hispanic researchers providing a Hispanic perspective.
9:59
I think a very nice example of this is the experience of cardio nerds with trial enrollment.
10:04
I also have to give kudos to Dr. Melvin Echols because I know he has been involved in this
10:08
and probably knows the statistics better than I do.
10:12
But cardio nerds through a diverse group of trainees have been able to increase recruitment
10:17
in the trials they have been involved and it is quite impressive.
10:20
They have been able to recruit over 50% of women and more than 80% of Black individuals
10:25
are people of color.
10:26
This has been a nice demonstration of how a diverse team leading trial enrollment here
10:31
in professional development can increase equitable trial enrollment.
10:34
Thank you, Dr. Blumer.
10:35
We're going to turn the conversation to policy.
10:38
Now that Dr. Ibrahim, who was part of our faculty at ANOVA and part of Mass General Clinical
10:43
Faculty is taking a year off to really understand policy in this area, Nasreen, can we do it
10:50
at a policy level?
10:51
One of the things I'm impressed about is how we can do trial after trial and make iterative
10:56
changes in outcomes.
10:59
Policy can make sweeping changes overnight.
11:02
The pediatric patent extension is a great example of how children were, again, afforded
11:07
the opportunity to be in clinical trials and have the advantage of clinical trials because
11:13
of that process.
11:15
And there's many other examples how policy has been favorable.
11:18
The NIH has that policy of targets.
11:20
It seems to me to have worked pretty well with a significant opportunity certainly to
11:25
improve.
11:26
But as you look at the landscape of perhaps the policy of how we approach diversity in
11:31
clinical trials, what would you say is an opportunity for improvement?
11:34
I think policy plays a huge role, like you said, in making these sweeping changes.
11:39
It's difficult though, and everything costs money.
11:42
So you have to think about, say, for example, if we're asking the FDA to mandate that pharmaceutical
11:49
industry has to create a diversity plan.
11:52
So where is this money going to come from?
11:54
Is it going to come from the FDA?
11:55
The FDA is going to provide financial incentives or is this going to come internally from the
12:01
pharmaceutical companies to create these diversity plans, just like the NIH asked for what your
12:05
diversity plan when you submit a grant proposal.
12:09
We can also think of the FDA providing grants.
12:11
We actually just discussed this an hour ago.
12:14
We had a noon conference on diversity in clinical trials and talked about potentially the FDA
12:19
providing grants to sites that are not well equipped or as equipped as the powerhouse
12:25
sites mentioned by several people on this panel to provide them the training, the clinical
12:30
expertise, whatever they need in terms of a staff to run a good clinical trial in a
12:37
space or in a neighborhood or a city, not the usual sites that we decide to include
12:43
in clinical trials.
12:45
The FDA can also provide tax breaks, but again, who's going to benefit financially from this,
12:49
but tax breaks to pharmaceutical industries that have included a diverse patient population
12:54
in their trial.
12:55
I think one big thing is we keep saying, why is this important?
12:58
Why do we need to do this?
12:59
And the professor just an hour ago said, if you have a drug that is for breast cancer,
13:05
but your clinical trial enrolled 60% men, then how can you say that the drug works?
13:11
So that's how we have to think about the trials that we're doing and where the money is going
13:16
to come.
13:17
But I think the FDA can play a big role in providing incentives to drug and device companies
13:22
to diversify enrollment.
13:24
Terrific comments.
13:25
There's a secret I'll tell you all about HF Action because of incentives and they were
13:31
incentives that you might not get your grant funded the next year if you didn't hit your
13:35
targets.
13:36
HF Action had enough power to demonstrate that actually exercise was more efficacious
13:41
in women than men.
13:42
Wayne, you don't need to go on the treadmill tonight, but Vanessa and Nasserine, Joanne,
13:47
you would benefit from it, but Wayne won't.
13:49
Mitch, you're sitting there in multiple hats working as a special employee of the FDA,
13:55
working as the head of heart failure at NOVA.
13:57
What do you think regulatory policy can do here?
14:00
Obviously, we've made some incremental movement.
14:03
It's bipartisan too, which is really exciting.
14:06
It's rare to see in DC anything bipartisan these days, but it seems like there is a bipartisan
14:11
belief that this has advantages for everyone in the ecosystem.
14:16
So what can the regulatory agencies do here?
14:19
They obviously can encourage, they can't mandate.
14:23
Tell us a little bit more.
14:24
I think that's right.
14:25
I think that as we heard from Nasserine, there are certain things the federal government
14:29
can do as a regulatory agency within the government.
14:32
The FDA can only do what it is allowed to by law and statute, but within the confines
14:39
of those barriers, we can incentivize companies to be more thoughtful about their inclusion
14:46
of traditionally underrepresented minorities.
14:49
And we can also make sure that data is clearly reported.
14:53
So not only in the collection of the data and the incorporation of patients in clinical
14:59
trials to improve overall equity, which again is the point, right?
15:03
The point of doing this is not that we can come up with, as you said, an age of action,
15:08
individually statistically significant differences between subgroups, because that is probably
15:14
not feasible in terms of the enrollment perspective, the number of patients you would have to roll
15:19
to do that for all what you think might be clinically relevant subgroups.
15:22
But it is to give a general sense that the effect that you're seeing and the safety that
15:28
you're seeing is relevant in the major populations in which the drug or device or other intervention
15:35
is likely to be used.
15:36
And I think that within that, the FDA has certainly a role.
15:41
And also if you look at the sharing of data, the communication of data that comes out of
15:47
clinical trials, that is also produced on the clinical trials communicator information
15:53
in terms of the demographics that are published for all FDA approved products.
15:58
So I think that is the role currently the FDA can have.
16:02
Certainly it could change if policy changes, but I think it is something that is acknowledged
16:06
it is something that we have that the FDA has partnered with NIH and others that can
16:11
have a more active role in withholding funding if this is not done and is something that's
16:16
going to continue to be encouraged within the federal government.
16:19
Terrific perspective, Mitch, from both angles.
16:22
I'm going to go back to Joanne here and ask her about, we worked for a decade on a journal
16:27
together, and we tried to look at the way publications were coming in.
16:32
We often saw that clinical trials did not have representation, women or underrepresented
16:39
minorities in the steering committees.
16:41
And you put forth a wonderful editorial suggesting that the journals could play a bigger role
16:46
in encouraging that publication should come forth describing the members of their leadership
16:52
teams and putting as a limitation if they didn't have representation, the broad spectrum
16:57
of clinical investigator leaders such as women, underrepresented minorities, that would be
17:01
a limitation.
17:03
Describe that and what could journals do more in this environment?
17:07
Prashil, you were a big part of that.
17:09
I think what we thought would be that if the leadership of the trial was not diverse, and
17:15
I don't know that every leadership group could be diverse in every way, but at least if they
17:19
didn't demonstrate diversity, that should be in the limitations of the study.
17:24
Why were they unable to have a diverse population?
17:27
And ultimately, I think that journals could require that to be a statement.
17:31
It's not huge, it's not really punitive, it's in the limitations, but I think it would first
17:36
encourage trials, put people on the steering committee who are diverse, which would then
17:40
encourage diverse enrollment.
17:42
So I think that's one thing journals can do.
17:44
I think they could ask editorialists to comment on the lack of diversity in both the trial
17:48
leadership and the enrollment of patients.
17:50
That's not unreasonable.
17:52
So I think every step of the way, every group that has a touch on the conduct of clinical
17:57
trials can probably do something to improve the way we do it.
18:01
I think there's lots that we can think about more in the communication venues that we help
18:07
the ecosystem building a more diverse community in the clinical trials.
18:12
Melvin, one of the things that you tackled when you were at Duke was what does the study
18:17
coordinator, the frontline person, look like?
18:20
And how important is that?
18:22
I would say it's incredibly important to the fact that, first of all, a lot of times coordinators
18:28
are going to be with the patients a lot more than the side PIs are, and they have to have
18:33
a nature of relation and the ability for the patients to trust.
18:38
But more importantly, the research coordinator needs to understand the true mission of what
18:42
you're trying to do.
18:44
And I think that's really important.
18:46
I started in Lumberton with one research coordinator, zero dollars, and we were able to be very
18:52
successful over a period of time.
18:54
But that research coordinator understood what we were trying to do, the purpose of enrolling
18:59
underrepresented populations.
19:01
And to that end, she understood the complete mission.
19:04
So it's very important for the research coordinators to be actively involved and to be a part of
19:09
the active team.
19:11
Terrific.
19:12
Let's go around the room with one takeaway comment to our audience and really to answer
19:18
the question, how can we do better as investigators, as trial leadership, as sponsors in diversifying
19:27
the population in our clinical trials, ensuring greater representation of underrepresented
19:33
minorities, women, and other special populations in our trials?
19:37
I'll start with Dr. Bloomer.
19:39
I think there's a lot of opportunities and I'm really excited that we're having this
19:43
conversation today.
19:44
I would say my key takeaway, and I could have many, but if I have to choose one, is that
19:48
we need to develop a diverse pool of investigators and staff.
19:52
And we talked about that.
19:54
But ultimately, I believe that the gender, race, and ethnicity of the investigators should
19:58
reflect the communities and the patients that we're caring for.
20:02
In addition to this, I do think that we should engage more junior generations who have an
20:06
interest in clinical trials, senior researchers should somehow provide a platform for a junior
20:12
individual, the researchers who are not only diverse, but also highly motivated to develop
20:17
themselves as trialists.
20:18
Terrific.
20:19
Wayne?
20:20
I think that emphasis should be placed predominantly on the most important stakeholder, and that's
20:25
patients.
20:26
We've got to do a better job of understanding the impediments from the patient's perspective.
20:31
There are a lot of reasons why patients either turn down research or don't continue to follow
20:35
up when you enroll, and much of that can relate to some of the challenges that relate to distance
20:41
to the follow-up institution, the hospital, or the clinic.
20:44
Some of it can be related to financial difficulties.
20:47
It costs money and time to participate in research.
20:51
I think we need to think about that and think about ways in which we can fairly compensate
20:55
patients for inclusion under the right circumstances.
20:58
I think we have to work on this dispelling myths about research, as mentioned before.
21:04
And then we also need to make the sites more capable of enrolling patients.
21:09
We've got to educate sites, develop new sites, and make sure that those sites are strategically
21:14
located in parts of the United States that just naturally have access to these underserved
21:19
populations.
21:20
And this includes patients who live in rural America.
21:23
That's a particularly challenging group to access for clinical trial enrollment.
21:27
So I think there's a lot of work that needs to be done.
21:30
I think that finally we're seeing multiple stakeholders coming together to work on this.
21:34
We're seeing a lot of interest from the regulatory side, the industry side, academic thought
21:39
leaders, and the cardiology community in general.
21:43
And we're actually going to have to do a better job of engaging patients as important stakeholders
21:47
in these discussions and our movement forward.
21:50
Great sage advice.
21:51
Nasserine?
21:52
I was going to say that as we're designing these trials, like Dr. Batchelor mentioned,
21:57
keep the patient in mind, make sure that when we're arranging how many follow-up visits
22:02
are going to be, what we're going to require of the patient, we have to keep them in mind
22:05
and make it not so time consuming that it's really not easy for somebody that's the CEO
22:10
of Fortune 500 company to take so much time off work and come in for these appointments,
22:14
but it might not be for the of less means.
22:17
So in the design of the trial themselves, make them patient friendly and that way we'll
22:22
be able to recruit more people that won't have to consume so many resources to be part
22:27
of the work that we're trying to do.
22:29
Terrific comments.
22:30
Mitch, you got to top that.
22:33
Oh, thankfully I don't have to because I'm really just going to reiterate what everyone
22:37
else has said.
22:38
I think that it is critically important to expand the investigator pool by bringing people
22:43
not only into kind of site-based leadership, but also clinical trial leadership on the
22:49
larger scale, apprenticeships within the clinical trial leadership, non-voting members, people
22:53
to educate, to bring clinical trials to more of the country and the world quite honestly,
22:59
to train the next generation of people that are coming from additional spots that are
23:05
not the kind of homogenous places where they're currently coming from.
23:10
And then just to reiterate what has been said about patients, there are many aspects of
23:14
clinical trial design where patients can have input and to improve the overall clinical
23:18
trial and evidence generation.
23:20
And it is in this area when it comes to patient recruitment, when it comes to inclusion and
23:25
exclusion criteria, when it comes to structuring the clinical trial, when it comes to educating
23:30
potential patient enrollees.
23:33
We saw what Adaptable did with having patients really on the front line of it helping to
23:37
encourage patient enrollees.
23:38
Involving patients in this process in a very aggressive way, I think will do wonders for
23:46
enrolling a more diverse population.
23:49
Well stated as always, Mitch Melvin, what's the take home message that our audience take
23:54
from you?
23:55
So Mitch absolutely took mine.
23:57
So there needs to be a lot of support in career development for the site PI as well as the
24:03
research coordinator.
24:04
I think that's very important so that they can see a path forward.
24:08
But also in the community, as we're talking about patients, the community needs to understand
24:12
the results of the trial.
24:14
Often times patients say, I was involved in this trial.
24:17
I don't know what the results were.
24:18
What can you do?
24:19
Can you give me any information?
24:20
So letting people know what the results of these trials are ultimately educates the community.
24:25
Really good point that we could delve into more at another time.
24:29
And just like our editorial board meetings, Joanne, you get the last word.
24:33
So Chris, a job for you.
24:35
I think the Heart Fetal Laboratory should lead a nationwide FDA CMS group to have something
24:41
like the Clinical Oncology Trials Network.
24:44
And within that, you would select diverse populations and within those diverse populations,
24:48
there would be salary money, money to trade junior faculty.
24:51
And that way we would have in perpetuity a large group of centers across the United States
24:56
who are training diverse people, who enroll diverse patients, where the communities now
25:00
understand their input.
25:02
It's up to me.
25:03
I think you're exactly right.
25:05
One of many of my greatest failures has been the inability to set up a sustainable network
25:11
that mirrors what oncology has done.
25:13
We tried to do that with the NIH.
25:15
It's not a sustainable model.
25:17
We go back to this sites come on, they come off, they come on, they come off.
25:22
It's like subcontractors working in the housing industry.
25:26
There's gaps of opportunity.
25:28
So having a national network of committed investigators that we know can participate
25:34
in this clinical trial endeavor that's diverse would be extremely important.
25:39
So Joanne, you got me on that one.
25:43
As she often did when we are in our editorial meetings, she always got the last word and
25:47
put me on the spot, but terrific conversation today.
25:50
Thank you all for being here for the Heart of the Matter Heartthrob Collaboratory podcast.
25:56
And we will certainly have you all back to discuss this in more detail.
26:01
Thank you very much.
26:02
européenne.ch