Disparities in Clinical Trial Enrollment

In this lesson, we will focus on disparities in clinical trial enrollment, why these disparities exist and what is being done to try to overcome them. Let's start this lesson by discussing what disparities are found in enrollment for multiple myeloma clinical trials. Why is it important to have diverse representation in clinical trials? The FDA has said that it is difficult to assume that the results of a clinical trial are pertinent to everybody unless people of diverse populations are involved in clinical trials. One thing that the FDA saw between 2009 and 2017 was that the enrollment of myeloma patients for FDA approved drugs or drugs to be approved by the FDA, only 4.5% were people of African descent. If you look at the United States, the number of African Americans that have myeloma in the United States makes up about 20% of the myeloma population, but only 5% are enrolled in those clinical trials. How can I know that a particular drug will work for my patients and only 5% of African Americans are involved in that? How do I know it will work for everybody? It's important to have a diverse population in clinical trials and know that these drugs work. If it works for one group, it doesn't work for all groups, and you can't cure myeloma unless you cure everybody. Enrolling diverse populations gives us more information. It gives us more closer to that cure, closer to those excellent treatments when we enroll diverse populations. In terms of clinical trials for the myeloma population, I think even without thinking about myeloma itself, we first have to kind of take a broader lens and ask who is actually enrolling in clinical trials more generally. We see that nationally, if you look across all cancer types, that Black patients continue to be underrepresented. They represent only about 7% of those who are enrolled in clinical trials, and that number is pretty similar for myeloma, especially myeloma-related trials. We need to have African Americans or Black patients represented in trials because this is a way for us to truly tell if these therapies that have been tested in other populations are as effective in the African American or Black community. Also, we need to remember that in the real world, when we're giving these drugs, if we haven't tested them in that particular demographic, it makes it really hard to understand what is the true effect of these particular therapies within the African American or Black community. So allowing us to study the direct effects, that really helps when Black patients or the African American community really can engage and participate in medical research. How do treatment side effects vary between different ethnic groups? The perfect example of this is Revlimid and Velcade. We now know there was a paper that was published in 2021 that showed that people who are on Revlimid, Black people on Revlimid, it causes darkening of the skin, so it makes their palms darker, it makes their souls darker. And it can be pretty distressing when you're taking a drug and then your palms turn dark. The Revlimid came out in 2002, and it took us 20 years to see the side effect of Revlimid, for that to be reported. That is because when the Revlimid trials came out, that less than 5% of the people on those trials were African American. 20 years to figure that out. And there was a paper that was published by the folks at Emory that showed that Black people have higher risks of neuropathy with Velcade. That just came out in December of 2022. So it took us 21 years to know that Velcade has this neuropathy risk for people of African descent. And it's because of the lower cruel numbers. Why is there under-representation of Black people in clinical trials? So in terms of disparities that exist in clinical trials, some of those include not presenting clinical trials upfront as a treatment option for many patients of minority backgrounds, and also recognizing that some of the eligibility criteria for clinical trials do prohibit some of these patients of being likely to participate. The reason for this, I think, is multifactorial. I really think it begins with, one, not having the knowledge and awareness about when a trial may be appropriate for them. And so this comes down to education. And so whether or not we are in the communities educating African Americans about the role of clinical trials in their care. The other part that it comes down to is thinking about the role that the providers play when thinking about who should be offered a clinical trial. We looked at this earlier at ASH, and we showed that there is a potential role of discrimination on the part of the providers where they make assumptions about patients that may lead to them not offering patients clinical trials. So with those two things, I think those really drive why we see this differential ability for Black patients in particular to enroll in trials. There's other factors that we always have to think about, and those include things like trust. And so a long history of medical mistrust really limits the Black population or the African American community from really trusting the medical research. And so that may make them more reluctant to actually want to engage in medical research. Because we don't have enough African Americans in clinical trials, the disparity is going to continue to be there. And I know that people, when they hear clinical trials, they automatically think about Tuskegee and the things that were done to Blacks back then and all of the say one thing and do another and the lies that were told to the people. Because that's ingrained in Black people, they always have a mistrust of doctors. They have a mistrust of trials because it sounds like you're going to be a guinea pig. You're going to be experimenting on you. And the only way to break that, I believe, is for doctors to say what they mean and do what they say. And then for patients to understand that this trial is to help other people. You're not a guinea pig. There is no cost involved in it, but it's there to help you. And so I really, really, really think that the trust has to be there between the doctor and the patient in order for the person to feel comfortable enough to go ahead with the clinical trial. Number one was fear of randomization, that they're going to be randomized to a placebo. In myeloma, when there's a randomized trial, it's either the best possible care, best care available versus the best care available plus a bit of icing on the cake. And so if you're enrolled in a clinical trial that's randomized, you will receive the best possible care. There's no way that will, any other way that will happen. And you might get the other drug, I'm saying the other drug, the best possible care plus a little bit extra. Is that little bit extra going to help or is that little bit of help just going to keep things the same? That's the point of the trial, but you'll get the best care no matter what. The other thing that people worry about, they're going to be a guinea pig in a clinical trial. The African-Americans worry about the atrocities that happened decades ago, which is still very prevalent, still very in the minds of researchers. But we've done a lot of work to ensure the safety of the clinical trials, that they're no one's a guinea pig anymore. There's lots and lots of training. To be an investigator in a clinical trial, you have to go through training and training and training and training to be absolutely certain that clinical trials are safe, that no one's a guinea pig. You're receiving the best care in a clinical trial for sure. The other worry is, will my family, the community engagement? And so talk to, if you're going to go on a clinical trial, talk to your family. Don't just make that decision by yourself. Talk to your family, engage your family and show them what the clinical trial and get their input. We want to hear that. I don't like seeing a patient talk about clinical trial when they're alone, because I know that's a lot of information. Bringing people around and engaging your family is so important and makes doing the clinical trial so much easier. To learn more about the history of clinical trials that led to medical distrust in the Black community, watch this Health Tree University video about the history of clinical trials and the healthcare system. What are some things that could be done to increase participation of Black patients in clinical trials? There's several things being done to increase African-American accrual in clinical trials. Some of those include adjusting the eligibility criteria for clinical trials to ensure that we're not necessarily boxing out patients who may have renal insufficiency, which is more common in patients who have long-standing hypertension or long-standing diabetes. There are certain hematologic conditions that are more common in African-Americans, including a lower neutrophil count. It's a normal phenomenon in some of these populations. So making sure that the clinical trials include that in the eligibility criteria, some of these are being considered. And also ensuring that the informed consent is written in such a language that is much more amenable and understanding to patients broadly, not just African-Americans, but most patients in general. How can we improve the accrual of African-Americans in clinical trials in the United States? And I think the very first thing is making awareness that there is a problem. I think that every mile on my doctor has an awareness, and the FDA is now very aware that we have an accrual problem. The second thing is, it's also already happened, that we needed to really make sure that investigators have an idea of how they're going to accrue people of different ethnicities and races in clinical trials. And the FDA in April of 2022 set up guidelines that every clinical trial that asks for an IND, which is the step before you open a clinical trial, has a diversity plan built into it. And that the investigators know for the trial how many people of diverse populations need to be included in a clinical trial. They set a number. They then make that accrual goal of different ethnicities and races, and then have a plan to maintain that. So that is built into the clinical trial paradigm, that when you write a clinical trial and when you want it approved, because every clinical trial has to go through the FDA for an IND, that they review that. And when I've talked to folks at the FDA about how well will you enforce that, they say, is part of the plan that you have to submit. So that's been achieved. So now the real question is, is how do we now we're ready for the boots on the ground? How are we going to get people actually of different ethnicities and races involved in these clinical trials? And I think the other part is awareness among the community, is having the community aware that they need to be involved in clinical trials. And I think that if the community saw that, you know, why do people go on clinical trials is for them to personally benefit and for it to benefit their community. We can now go to the communities of ethnicity and races and say, this is why you should be on the clinical trial, that when people of diverse populations aren't on clinical trials, we miss efficacy and we miss side effects. And then the other thing is to decentralize clinical trials. That right now we have what, about 24, 25 myeloma centers that accrue patients of clinical trials. And we know that people of different ethnicities and backgrounds, people of different socioeconomic status, older people, don't engage these big medical centers. And so their efforts right now to try and decentralize clinical trials, instead of the patient leaving their home, leaving their community to come to a big institution for a clinical trial. Well, let's bring the clinical trial to them and make it at their doorstep and make it at the clinic that they're at. Trial enrollment can be looked at from many facets and say, well, yeah, there's many problems to tackle here. Is it about trust? Is it about historical injustices? And those are all relevant issues. But I think there's certain really easy low hanging fruit. When you speak to patients about enrollment in studies, ultimately, and this has been studied as well, ultimately people are people. If they trust you, if you trust your doctor, and if you're offering something that could actually benefit them, then in my experience, patients don't say no. So I think one of the major things that we really need to do right now is say, look, there needs to be a minimum number of African American, Hispanic patients within the context of studies. And that's going to reflect our community if we're going to approve drugs. This is not a small thing. But how do we get those trials to people? We just need to open up in their community. So we need to open up trials where patients are seen. The truth is that many of these patients go to different hospitals. And that's for many reasons. That's financial. That's because of payers. That's also because of distance. So we need to make sure that we don't neglect entire segments of our community in terms of where we open up trials. I think very similar ideas go for rural communities where we have similar data that rural communities don't get access to many of these treatments. There's a lower utility of things like, utilizations area of things like stem cell transplant. So same deal for those communities. We need to make sure that we're opening trials at centers that serve those communities. So it's a big question. It's a very complex question. I think there is a lot to unpack there. But if we say that there are doctors that this community trusts, they should have access to those studies. And they will reliably put those patients on trial. I can guarantee you. So in order for us to really think about strategies to build, bridge this gap, we need to be thinking about strategies on multiple levels. We need not only to be thinking about how we build trust with individuals, but we also need to think about ways in which we make our institutions more trustworthy, that patients will feel comfortable coming to us and seeking out trials. We also need to be focusing on increasing education and awareness, especially in the African-American community, so that they recognize the value of participating in clinical trials and recognize that their input is truly necessary. To summarize, we've discussed disparities that exist in clinical trial enrollment, why diverse populations are needed in trials, and some ways to begin to make trials more diverse. Education and awareness were discussed as ways to increase diversity in clinical trials. To learn more, we encourage you to check out our video about clinical trial myths.