Diversity in Clinical Trials: Understanding Common Perceptions

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic.

Ashish Sarraju, MD:

Hello everybody. My name is Ashish Sarraju. I'm a staff cardiologist here at the Cleveland Clinic and a researcher at the C5 Academic Research Organization. And I have here with me Jenn Mitchell, who is a project manager here at the C5 Academic Research Organization. And Jenn, today we're going to be talking about diversity in clinical trials, what it is and why it's important. So Jenn, what are your thoughts on this?

Jenn Mitchell, RN:

Well, I've been a study coordinator in the past. I'm a project manager now, so I've seen a little bit on the other side. And I've also been a patient and I've had my parents that would've been great for research and they didn't want to be into research unfortunately, due to probably some misconceptions about research due to us being a minoritized population. But we can have a discussion about that. And I could tell you a little bit about my history, but we can talk about really what defines diversity according to you.

Ashish Sarraju, MD:

Absolutely. So diversity in the context of clinical trials relates very closely, I think, to inclusiveness and equity in the way we perform our science. So we're talking about ensuring that when we study a condition, we study a new therapy for a condition, we study the people who have that condition in a fair representative manner by age, by biological sex, gender, race, ethnicity, geographic origin. These are all categories by which we want to make sure that we're not excluding patients with that condition from our studies of that condition. And that's where diversity and representation in clinical trials I think becomes really important.

Jenn Mitchell, RN:

I agree. Are there any inclusive language that we as healthcare professionals should know? I know there's always updating language that we might not know about yearly, sometimes it seems like monthly that we should really know and understand as we go through.

Ashish Sarraju, MD:

Yeah, that's a great question. And language is such an important part of this entire process. The idea behind including language is to, one, make people feel included and build trust, but also help us learn and change the way we think about things, our own mental concepts. One guide, for example, that I find very useful is the American Heart Association's Guide on Structural Racism and Health Equity where they go through terminology in a very detailed manner. But really we can start off with simple things like when often trials when they describe race and ethnicity, they use the term Asian. It's very common, but we could be a little more inclusive there.

We could try to disaggregate that group into Indian, Chinese, Vietnamese origin. These are disaggregated Asian groups that have different health characteristics and different backgrounds. So I think disaggregated language is a big part of it. Also, language that acknowledges the historical context of equity and structural racism is a great place to start. Like you just said, minoritized populations as opposed to minorities. The former term in some way, at least mildly acknowledges the historical context behind the population becoming disenfranchised or minoritized. So I think thinking about language in a deliberate manner when it comes to diversity and equity is a very important part of the process.

Jenn Mitchell, RN:

I agree. Exactly. How is the lack of minoritized representation, how is it impacting trials and even future patient care as a whole? How would you think?

Ashish Sarraju, MD:

Yeah, that's a great question, right? I think part of it relates to building trust. We have poor representation from several minoritized populations because of several reasons. But one main reason, as you alluded to, and I'd love to hear your thoughts about this, is a historical mistrust. And that the field of medicine has in some ways brought upon itself through research, ethical violations and experiments in the past that have engendered mistrust in the research sort of organization. And because of that, we're going to see a level of skepticism, a level of hesitation from different populations and participating in clinical trials or experiments, which essentially is what a clinical trial is. It's a scientific experiment. So we have that.

We have logistical barriers, financial barriers. In many ways, the ability to participate in a clinical trial is an indicator of a certain level of availability of resources. You have time, you have the money to travel, you have the access to transportation. You're not under other pressures. You can take a few hours out of your day once a month or maybe even more frequently to do this. So on some level improving trial participation is closely related to improving access to healthcare resources across the board. But that again, is a major barrier. And what we see is if we don't do this we're essentially not trying to improve the mistrust that's already there. Now, if we continue to do clinical trials without representing everybody, again, that cycle of mistrust is very unlikely to be broken. Second, when we study a therapy, we need to make sure that the effectiveness of that therapy and the safety of that therapy is the same across all the patients who have that condition. So representation from a scientific standpoint becomes important. I will say there sometimes the numbers aren't large enough to look for differences between groups within a trial when it comes to the statistics, but still including everybody and giving ourselves the best shot of making sure there's no heterogeneity or differences in treatment effect between different groups is very important.

Jenn Mitchell, RN:

Right, exactly. And what you're saying about what I mentioned before, even with my parents, I try to get them in a trial and my mom was like, "Nope." She was adamant. My dad was like, "Nope." Because they think clinical trials, they think of Tuskegee, they think, "Oh, I'm going to have to pay." Or, "I'm going to be a lab rat." Or, "They just want me because I'm a minoritized population, they just want me to be a token, a quota. And they really don't care. They're just trying to hit what they need to hit and then that's it.” They don't really want to participate. So I tried, it would've been great, but there's nothing sometimes you can do. And sometimes even as a patient, sometimes on the other side, you might not be approached to be into research because they think automatically I may say no. And they might just skip over me and I won't say no. And I know a lot of people might not say no, but they just might think, "Well, I'm not even going to waste my time." And just continue on. So some others might be skipped just on the other side as well. So it's kind of a flip-flop. And even as a study coordinator, I try to recruit everybody. And no matter what they would think, whatever the patient, and sometimes there's varied reasons why some people had a decline, but a lot of people were very interested and sometimes some people just had to decline and some people were interested and got in. There's all different reasons why some people just couldn't get in or they got in or whatever. But sometimes it's just that misconception already there on both sides. So that's a little bit difficult, I think, but we have to change that. It's going to be a while, but that's changed a long while.

Ashish Sarraju, MD:

Right. And thanks for sharing. And you have such a unique perspective, right? Because you were consenting patients, you were hearing that firsthand, and you're really experiencing that on the ground.

Jenn Mitchell, RN:

Exactly. Yes, I did. That was hard. And some people think they have to pay. Sometimes it's different. But we see patients all over the world here as well, a very diversified patient population. So that is a good thing. Why is it important to have such a minoritized representation in clinical trials, especially with the cardiovascular trials that we majority work in here at the Cleveland Clinic? And what kind of challenges do you face, especially as physicians that see these patients ongoing even after the trial's in, what do you see?

Ashish Sarraju, MD:

Yeah, no, that's a great question. So first to the first part of the question, why is it important? We touched on it briefly earlier too, but just again, to drive the point home, right? One, it's about building trust. Okay? It's about building trust and fairness within the communities. It's about showing that the clinical trial organizations in the field of medicine as a whole is interested in reaching out and making the effort to overcome the historical mistrust, okay? Second, it's about representativeness so that we can make conclusions about how good our therapies are in a fair manner for everybody who has the condition. So those two are extremely important reasons why diversity is important.

But again, we have challenges like the ones you just mentioned, logistical cost, transportation, trust, time burdens, and these are all things that we see in routine healthcare when we see patients. These are the things that often prevent patients from getting routine healthcare. And a lot of that mirrors, I think, the same barriers that patients have when it comes to clinical trials. So it's in many ways a mirror of modern healthcare. Trial diversity barriers are a mirror of healthcare in general.

Jenn Mitchell, RN:

I agree. I totally agree. So what cardiovascular trials that you have seen while you've been in a role that have had actually good examples of diversified or good diversity in the trials themselves? I know there's been opposites to what we have talked about.

Ashish Sarraju, MD:

Yeah, absolutely. And one recent example from right here at C5 was CLEAR outcomes, which enrolled almost 50% women, right? And that's great. What may be useful to chat about here are strategies, what can we do? And we've talked about what the issues are at length, and I know we can talk about that for a long time. But what can we do? Well, I think there are a number of things that as clinical trial organizations think through this, pharmaceutical companies think through these. It starts at the planning stage. It starts when you're making the protocol, to make this a priority, to make this a quality metric when you're doing quality control of the trial, which is a routine part of trial planning. Second, it's about diversity in the leadership as well. So it's not just the patients. So when you think about creating the academic leadership team, the data safety monitoring board, the executive committee, the principal investigators, the site investigators, having diversity within that group is a good way to ensure that there are going to be people on that trial leadership who have an opinion that's different from the way traditional clinical trials are conducted, who can maybe make inroads into this a little bit. Third, I think deliberate planning around barriers. So is there a way we can mitigate transportation costs in an ethical manner? Are we making sure that trial materials, pamphlets, flyers are translated into different languages because we don't want language to be a barrier. So thinking through all those things in a deliberate manner and making diversity an inherent trial quality metric and ensuring diversity at the leadership level, in my opinion, is a good place to at least start this process.

Jenn Mitchell, RN:

I agree. Since we're both into cardiovascular research, so within C5 research and HVTI, what are some goals that we can strive through? I know you mentioned a lot of those to achieve, so we can have more inclusive enrollment in a lot of these trials. We have a lot of new ones coming in. We have a lot of active ones, but a lot of these new ones coming in, we're heading into a new year. We're halfway into 2024, 2025’s coming up. So how can we get some more inclusive enrollment with these new trials coming up?

Ashish Sarraju, MD:

Yeah, no, great question. And we've seen already with CLEAR outcomes and of the other trials that I've been involved in, we've already seen that a lot of the times diversity has become a quality metric that's tracked with executive committee meetings. We've seen diversity in executive committee and leadership composition, okay? So we're seeing these steps already implemented. So I think just building upon these, looking at the sites, making sure the site investigators are diverse. Making sure we're building relationships with community leaders and community partners who can help us make inroads into sites that we otherwise may not consider. And thinking about strategies that can reduce logistical burden, so digital recruitment, online recruitment, virtual recruitment, things that maybe mitigate the need for patients to travel from one place to another. These are all some cutting edge things that we can think about as the trial design evolves.

Jenn Mitchell, RN:

Right, exactly. I know that's been a big thing. The government just passed the FDORA, F-D-O-R-A. So that hopefully will be into effect hopefully by the end of year going into 2025 because we'll have action plans so we can make sure we hit those metrics and make sure our trials are more diversified, hopefully. But I know we have a long way to go. That is for sure. Dr. Sarraju, it's been a pleasure. I know we just hit kind of the tip of the iceberg. We have so much work to do, but I think we have done a lot of work. We really have. Thank you for joining me for this podcast, and like I said, we have a long way to go.

Ashish Sarraju, MD:

Thank you, Jenn. Thank you for sharing your perspectives, and this was a great discussion.

Jenn Mitchell, RN:

Yes, thank you so much.

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