We live in an increasingly diverse world, and in order to deliver the best quality healthcare, we need to embrace and improve patient diversity in clinical trials. But how do we improve clinical research and expand treatment access to a more diverse patient population? In the second and final episode of our Clinical Research Series on the Science with a Twist podcast, our host Lloryn Hubbard welcomes Nik Kolatkar, VP of Scientific Operations & Evidence Generation at Genentech. They discuss the impact of inclusive research on drug development and decentralized and virtual study approaches that can reduce barriers and improve clinical trial participation for disenfranchised groups.
⚡ What are the ramifications from a clinical research perspective if diversity is not appropriately represented in a clinical study populations? Even as diversity becomes increasingly important across different sectors, minorities continue to be left out of clinical trials and medical research studies. So, why is diversity so critical in clinical trials? Nik explains, "I think in terms of the ramifications if diversity is not appropriately represented — I think we, unfortunately, saw this clearly playing out during the pandemic when we were seeing a lot of the data emerging that many underrepresented patients, particularly black and Hispanic patients, were having worse outcomes with COVID. Yet when we were looking at a lot of the trials for vaccines and therapeutics, those patients were not being included in the studies. And then as a result, from a scientific standpoint, when the results of the studies came out, people were understandably questioning, ‘Are these results that we're seeing generalizable to all the patients with the disease and especially the patients who're having the worst outcomes?’"
⚡ Recruiting and enrolling more representative populations does not mean delaying the study. Despite what many people think, enrolling diverse populations in clinical trials won't slow down the process. Nik shares his experience with including underrepresented minorities in peri- and post-approval studies through decentralized clinical trial models. He says, "The great thing was that not only did we complete that study and we had the data and that really gave us a lot more confidence in our medicine but also that trial recruited in record time, which was one of the myths that people had been saying, 'Oh, we could have a more diverse trial population, but it's going to slow the study, and we don't want to do that.' So, this study, we had 84% from underrepresented populations and actually was one of the fastest studies that Genentech ever enrolled and was published in the New England Journal of Medicine."
⚡ Clinical trials must strive to be more diverse. Enhancing diversity in clinical trials is a win-win for the entire public health system, not just for underrepresented populations. Nik explains, "We're thinking about this very carefully at Genentech, and we're trying to make sure that our efforts in terms of improving diversity in clinical trials is not just a one-off thing, that we really make this part of just the routine way that we do every clinical trial."
He adds, "I think our vision, as I mentioned, is that we really need to make enrolling a diverse and representative population a routine part of how we conduct all of our trials, which will not only increase the robustness of our research, but it will also help ensure broad patient access, and as we've seen from a few studies, not only will it not slow down studies but if done right can even accelerate trials. If we can do all of that, that can really represent a true win-win for patients, for us as a company, and for society as a whole."
[00:00:00] Nik Kolatkar: During the pandemic, we were seeing a lot of the data were emerging that many underrepresented patients, particularly black and Hispanic patients, were having worse outcomes with COVID.
[00:00:10] Yet when we were looking at a lot of the trials, those patients were not being included in those studies. And then, as a result, from a scientific standpoint, when the results of the studies came out, people were understandably questioning, "Are these results that we're seeing generalizable to all the patients with the disease and especially the patients were having the worst outcomes?" Hello. Welcome back to Science with a Twist. My name is Lloryn Hubbard. I'm the Director of Patient Diversity at PPD, part of Thermo Fisher Scientific. Safety and efficacy of drugs and biologics can vary depending on the intrinsic and extrinsic factors of our patients. So ensuring that clinical trials adequately represent the population's most affected by disease is critical.
[00:01:22] Lloryn Hubbard: It aligns with ensuring strong science, patient safety and evolving regulatory requirements. Most importantly, we, as an industry, are obligated to leave the way in developing effective and safe products for all patients. For this episode, we are joined by Nik Kolatkar, VP of Scientific Operations and Evidence Generation at Genentech, to discuss the importance of diversity, equity and inclusion in our clinical trials and how Nik and his team are working to ensure diverse populations are represented in their clinical trials.
[00:01:52] Nik, welcome to Science with a Twist.
[00:01:55] Nik Kolatkar: Hi, Lloryn. Thanks for having me. Great to be here.
[00:01:57] Lloryn Hubbard: No problem. Glad you're here. I think it's important to begin our discussion today with a really clear understanding of three principles of diversity, equity and inclusion. So can you talk us through the meaning behind each, specifically to help our audience gain a deeper understanding of the underlying barriers and value of meaningful implementation of these elements across clinical studies and, of course, through Medical Affairs?
[00:02:22] Nik Kolatkar: Sure, Lloryn. So I think it's, yeah, really important to set, set the stage with, with some of the definitions. And, um, it's been helpful that FDA actually had came out with guidance to industry o on this topic, initially back, I think going back to November of, of 2020, and has since updated some, you know, updated draft guidance in April of, of this year.
[00:02:41] And it's specifically really around the topic of d diversity, plans, you know, that sponsors should be thinking about in terms of how to improve enrollment of participants from, from underrepresented minorities in clinical trials. But it does provide a nice framework, I think, for how to think about diversity,
[00:02:57] Nik Kolatkar: equity, inclusion, the setting of clinical research. I think to make it simple, I sort of distilled it down from, from the guidance, but essentially diversity is really making sure everyone is represented. Equity is more about being fair to everyone who's involved. And then inclusion is really about creating a welcoming environment, you know, for, for everyone involved.
[00:03:17] So that's sort of how I think about the three. And, and each of the three are important.
[00:03:22] Lloryn Hubbard: Totally. Completely agree. I think, also just one way to improve health equity is through diverse representation in clinical trials, as we all can agree, where treatments are really first beginning to be tested. So how do you work to ensure diverse and underrepresented populations are participating in clinical trials?
[00:03:39] Also like what are the ramifications if diversity is not appropriately represented in a clinical trial population?
[00:03:47] Nik Kolatkar: Yeah. So one, I think one thing where we, where we've realized where we need to start off with really before we even get into a clinical trial, is just a good understanding, you know, based on the literature of, of the epidemiology of the disease for that particular trial in terms of race and ethnicity. So, you know, whether it's breast cancer or lung cancer or, you know, neurologic diseases or ophthalmologic diseases, you know, we need to know what does the epidemiology look like in terms of race and ethnicity,
[00:04:16] because it varies substantially by disease, right? So the, the percentage of black or Hispanic patients with diabetic macular edema could differ quite substantially from that in multiple sclerosis or triple-negative breast cancer. So I think, you know, we start off with really doing a, a very thorough look of the literature, and that that gives us a benchmark essentially for what we're striving for in each study.
[00:04:40] But that's only, you know, part of the puzzle. I think then we really need to help, you know, to your point, ensure that diverse and underrepresented populations actually part in the clinical trials. And there, I think, we really start from the beginning in terms of the design of the study and making sure that we're meeting underrepresented patients where they are in the community.
[00:05:00] Not only in terms of site selection, but also in terms of, you know, making sure we have multicultural patient materials, you know, in, in multiple languages, and making sure that our investigators are, are trained, you know, and how to present the, the study in a culturally sensitive way in a way that builds trust, you know, amongst the, the patients we are looking to participate.
[00:05:21] So I think so, so those are some of the key things we're doing. I think in terms of the ramifications, if diversity's not appropriately represented, I, I think we, unfortunately, saw this clearly playing out during the pandemic, actually. You know, we were seeing a lot of the data were emerging that, that many underrepresented patients, particularly black and Hispanic patients, were having worse outcomes with COVID.
[00:05:43] Yet when we were looking at a lot of the trials, you know, for, for vaccines and therapeutics, those patients were not being included in those studies. And then as a result, from a scientific standpoint, you know, when the results of the studies came out, people were, were understandably questioning, you know, "Are these results that we're seeing, you know, generalizable to, to all the patients with the disease and especially the patients were having the worst outcomes?"
[00:06:09] So I think, we saw that kind of play out in, in real-time in COVID. And that was where, as a company, Genentech actually, you know, was, was seeing that happening in real-time. And we, we started a dedicated, underrepresented minority study inpatients with COVID-19 pneumonia called EMPACTA, which was a study of one of our medicines, tocilizumab.
[00:06:31] Nik Kolatkar: And, um, we enrolled 389 participants with 84% coming from underrepresented populations, and was really the first study to do that. And that was a positive study, and really helped give us confidence that we knew that our medicines worked in all patients. And it complimented some of the other studies we were doing.
[00:06:52] And, and the great thing was, not only did we complete that study, and we, we had the data and, you know, really gave us a lot more confidence in, in our medicine, but that trial also recruited in record time, you know, which was one of the myths, you know, that, that people had been saying that, "Oh, we could have a more diverse trial population, but it's gonna slow down
[00:07:12] the study, and we don't want to do that." So this, this study, you know, we had 84% from underrepresented populations and actually was one of the fastest studies that Genentech ever enrolled and, uh, was published in The New England Journal Medicine. So it was really a, a, a great result overall.
[00:07:28] Lloryn Hubbard: That's amazing. 84% is super impressive. And I also think that to your point around COVID, just the idea that we were all in this pressure cooker to deliver these patient populations and we all did it. And so it really did remove any of the bias or the preconceived notions that we couldn't enroll diverse patient populations,
[00:07:46] right, especially in the US. So I think that's just really a, a really good take home that, you know, the idea that diverse populations are harder to find. Sure, they might be more challenging, but we can do it as an industry. We've done it and COVID really showed that. So I think that's awesome. We know that inequities in healthcare have long existed and that disenfranchised populations have felt the ramifications of disproportionate access and care. So Genentech recently invested in a study to dig deeper into those perceptions and experiences of disenfranchised individuals to identify challenges, barriers and opportunities to improve health equity.
[00:08:22] Can you please give us a quick overview of the key findings from this study? Is this the same study or is this a different study?
[00:08:29] Nik Kolatkar: So this is actually a survey that Genentech started back in, in 2020. And this was led by our chief diversity office, and it's been repeated on an annual basis. And essentially, this is an online questionnaire which included roughly 2000 US patients. And it was essentially a thousand patients from the general population and then another thousand
[00:08:52] who specifically identified as in terms of being part of one of four groups and, and that was black, Latinx, LGBTQ+, or low socioeconomic status. And then in addition to the 2000 patients, the survey also went to around 400 healthcare providers who are, who are either physicians, nurses, or pharmacists and, and physician assistants.
[00:09:15] And really it was asking questions around inequities in the US healthcare system and kind of trends over, over time. And you know, it's a detailed survey, and some of the results on the Genentech website, but just in summary, I think some of the key findings were more than half of the medically disenfranchised patients.
[00:09:33] So I think it was 54% actually in the survey. But felt that essentially that the healthcare system was kind of, was essentially rigged against them. And they kind of overwhelmingly agreed that healthcare inequities had worsened over the course of the pandemic. 'Cause we had, we've had a chance to look at these data from 2020 to 2022.
[00:09:54] And healthcare providers also similarly agree that the system does not really seem to be serving patients, you know, as it should. And only about half of about 50% of, of healthcare providers really felt that the system was acting in the, the best interest of society as a whole. And I guess importantly, about 80% of healthcare providers also felt that health misinformation or lack of trust was kind of a serious threat to the system.
[00:10:22] But I think one thing we did find, you know, where there was agreement between both healthcare providers and patients really was that a positive trusting relationship with, with a patient's healthcare provider is one of the key factors in terms of building trust in the system overall. And we're finding the same thing in our clinical studies.
[00:10:42] So the, the trusting relationship between the investigator and the, the participant is, is super important in terms of patients, you know, wanting to be part of clinical research.
[00:10:52] Lloryn Hubbard: Really interesting. So bring us to present day. So based on these findings from this survey, what steps is Genentech taking now in, in clinical studies to make this research more inclusive? And I think you just were trying to touch on it a bit.
[00:11:07] Nik Kolatkar: Exactly. So we're really, as I mentioned, starting with, you know, making sure we have a good understanding of the epidemiology and disease. We're really looking very closely at our site selection to include both community-based and urban-centered sites, you know, who have access to, to large underrepresented populations.
[00:11:27] But then beyond that, I think we're also really trying to make sure we recruit investigators who have experience in enrolling patients, you know, underrepresented patients into clinical research and also a passion for health equity research. Because that passion comes through, you know, in how they present the, the trial to patients and, and in their ability to build trust with their communities.
[00:11:50] And then finally, we're trying to also break down, you know, any logistic barriers that maybe hindering patients from being able to participate in research. So in terms of simplifying the logistics of, of trials, simplifying things like transportation to study visits. So making, um, we're working with a number of different transportation providers to essentially create like a, essentially provide like an Uber-Like service that patients can just, you know, basically get free transportation to the trial without having to worry about
[00:12:21] Nik Kolatkar: traffic and parking and, and all of that.
[00:12:23] Lloryn Hubbard: Right.
[00:12:24] And then finally, I think, yeah, making sure we're utilizing multilingual and culturally sensitive patient materials, which is very important.
[00:12:32] Lloryn Hubbard: Yeah, all of those are really great steps. I think that especially about the sites, being able to effectively enroll and communicate and make those patients feel comfortable, make patients from underrepresented populations feel comfortable is so important. So it is powerful to hear how Genentech is actively taking accountability and moving the healthcare systems towards equity in partnerships. We know it's critical for a clinical trial population to accurately represent the real-world population who will be taking the drug to ensure the best healthcare products are developed to help the people who need them most.
[00:13:05] As is typical in the industry, many global pharma and biotech companies partner with contract research organizations, CROs, to support key clinical research functions, including solutions to ensure accessibility and diverse patient recruitment, which has been especially challenging and enlighting during the pandemic.
[00:13:24] Genentech in the peri- and post-approval studies team of PPD, part of Thermo Fisher Scientific, recently partnered on one such solution, a decentralized clinical trial, or as we call DCT. So let's talk about DCTs and what they mean for patients and drug development. First, can you explain what a DCT is, what they are, and the critical benefits of virtual trials? And possibly share an example of a recent DCT Genentech study that was executed.
[00:13:51] Nik Kolatkar: Sure. So as you said, decentralized clinical trials or DCTs is, um, there's, there's sort of a lot of buzz about this term right now. But, but at its core, it's, it's really very simply just about essentially democratizing clinical research and, and improving the patient experience by meeting patients where they are instead of having them come to
[00:14:14] kind of the ivory tower for clinical research, you know, which had been the old sort of more traditional paradigm. And I think, I mean the, the reason why it's called decentralized is it, it's, it's essentially yeah, trying to move the clinical research, you know, where the clinical research happens kind of closer to the patient, as opposed to centralizing it in, in these ivory towers.
[00:14:36] And, and you hear that same terminology, you know, there's a lot of parallels to, you hear a lot of talk about decentralized finance, for example, with, with blockchain. And, and you know, that's the same concept of, you know, how do you make finance more secure, more convenient, more efficient for consumers, you know, to access without needing to go through the large banks.
[00:14:56] So, you know, from a clinical research perspective, I mean, our approach to decentralized trials is really to take kind of a, a patient first approach to think about, you know, how a decentralized trial might help to improve either quality, speed, cost or the patient experience. Because I think unless a decentralized trial is driving improvement in one of those things, you know, it may not be the right trial to, to do a decentralized trial in.
[00:15:25] So, for example, we do many complex cancer trials, which require IV infusions, you know, for where the patient has to, to come in to, to get that as well as hospital monitoring or complex imaging. And in that kind of trial, you know, a decentralized approach may not necessarily make sense because the, the patient has to come to a, a hospital or to a center to do all of that.
[00:15:49] Nik Kolatkar: But, but in other situations where you might have an oral therapy or a subcutaneous therapy or something that doesn't require a lot of sophisticated imaging, then you can do a lot more at the patient's home, you know, to, to make it more convenient. And, and a great example of this was actually a trial we did in collaboration with, with PPD, and this was with one of our medicines, called PHESGO, which is a fixed-dose combination of pertuzumab and Herceptin for HER2-positive breast cancer.
[00:16:19] And the great thing about PHESGO is that it combines the two medicines into a single subcutaneous injection that does not require in-hospital monitoring and really can be given at the patient's home. And the trial we were doing was, was actually an expanded access trial for PHESGO, which would allow patients to get access to, to enroll into the trial and get access to, to PHESGO before the, the drug was approved.
[00:16:45] And the trial was starting, you know, right at the start of the pandemic, where patients were really hesitant to, to go into clinics to see their doctor or, to get infusions or things like that because of their fear about getting COVID. So actually, we decided to do the PHESGO early access program as a decentralized trial.
[00:17:03] And we essentially, you know, we were able to, you know, use home nursing and video conferencing to essentially allow patients to, you know, get, get the medicine and have their visits from their home. And we used remote kind of patient education to help answer questions and remote platforms, you know, to help collect some of the clinical data. Which was really a win-win for both the patients, you know, who, you know, where it was much more convenient and they didn't have to worry about the risk of, of getting COVID by going in.
[00:17:34] And also for us, because it was more efficient and convenient for patients. So that, I think that was a great example of, you know, industry working together with our CRO partners and using a decentralized, you know, paradigm where it made sense for patients to really achieve a win-win.
[00:17:51] Lloryn Hubbard: Awesome. Improving diversity within clinical trials is critical to begin closing gaps in healthcare equity and to better develop drugs that serve populations and people who need them most. Where do we go from here to ensure that we as an industry continue to consider the care pathway for people from diverse backgrounds?
[00:18:12] How do we improve clinical research and expand treatment access to a more diverse patient population?
[00:18:19] Nik Kolatkar: Yeah. It's a, it's a great question and, and we're thinking about this very carefully at Genentech and, and we're trying to, you know, not make sure that our efforts in terms of improving diversity in, in clinical trials is not just a one-off thing that we really make this part of just the routine way we, that we do every clinical trial.
[00:18:38] We did the EMPACTA study that I mentioned earlier during the pandemic where we had a very good experience in terms of being able to recruit to largely, you know, minority study and record time with very high quality and really helped, you know, compliment our other trials in terms of our, you know, more robust scientific evidence in, you know, underrepresented population.
[00:18:59] Nik Kolatkar: But we wanted to make sure that wasn't just a one-off for Genentech. And we wanted to see could we, could we replicate that in a non-pandemic setting because there were a lot of unique aspects to the, to the pandemic. So we wanted to say, you know, "Could we do the same thing in, in a more chronic disease?"
[00:19:15] We took a look at a, a lot of our therapies and chronic disease, and what we realized was in multiple sclerosis, we, we have, really an industry leading therapy called OCREVUS. But what we realized was that in, in the OCREVUS registrational studies, we did not have very robust, you know, representation from underrepresented minorities.
[00:19:36] Nik Kolatkar: So we said, "You know, this could be a great opportunity to run a, a dedicated study to generate evidence with OCREVUS and underrepresented minorities and make sure that results that we found in our pivotal studies are also broadly applicable to all patients with, with MS."So we ran a study called CHIMES.
[00:19:53] And this study is still ongoing, but is now fully recruited. And where we recruited around 200 patients with multiple sclerosis. And this time 100% of the trial were was underrepresented minorities. And here we were able to, again, recruit a hundred percent of this trial with black patients, as well as Hispanic patients, in, in the US.
[00:20:14] And, and we also, for the first time, included patients outside of the US in, in countries that were also underrepresented from global trials. So we included patients in CHIMES from Kenya, in Africa. Because one thing we've realized, too, is that even though Africa represents almost 25% of the global population, less than 1% of clinical trials, you know, include patients from Africa.
[00:20:39] So, you know, we thought this could be a good op opportunity to also, you know, include a country and a site in Africa, which was very well equipped to run clinical research. And where the, with the local country felt that by generating some data in, in Kenya, it could help them in their, in their discussions with their local payer to get broader reimbursement in Kenya, as well as accelerated regulatory approval.
[00:21:03] So that, the good news is that trial is now fully recruited, has over 200 patients in it, and it, and also just like EMPACTA, it recruited in record time. So we, we recruited that study almost three months early that we're expecting data from that study in Q4 this year. So that's just another example of, of really where we're trying to make sure that these are not one-off studies.
[00:21:26] And the goal then is to take the learnings from CHIMES in multiple sclerosis and to feed that back to our pipeline programs so that our registrational studies can also become more diverse from the outset. And, and we've done that. So the, the learnings from CHIMES we've now fed back to a phase three study we're doing with an investigational molecule in multiple sclerosis.
[00:21:49] And they're including many of the same sites and taking some of the same learnings from CHIMES into our pipeline.
[00:21:55] Lloryn Hubbard: Very cool. Really impressive stuff, guys. I mean, a hundred percent is unheard of these days. And the idea that you also went to Africa, which is a very missed market, if you will, in clinical trials, is just really, really amazing. So as we've heard from you, there is real opportunity to make a significant progress in the education and importance of diversity in clinical trials. So what is the vision for your work in the future?
[00:22:20] Nik Kolatkar: Well, I think our vision, as I mentioned, is that we really need to make enrolling a diverse and, and representative population really a routine part of how we, how we conduct all of our trials, which will not only increase the robustness of our research, but it, it will also help ensure, you know, broad patient access. And as we've seen from a few studies, now can not only will not slow down studies, but if done right, can even accelerate trials.
[00:22:49] And if we can do all of that, that that can really represent a true win-win, you know, for, for patients, for us as a company, and for society as a whole. So that's kind of our overarching vision here.
[00:23:03] Lloryn Hubbard: Nice. Nik, thank you so much for sharing your experience with us and the work you're doing to prioritize patient representation and addressing barriers in clinical trial diversity and health equity. We live in an increasingly diverse world, and to deliver the best quality care, we must really embrace and prioritize diversity by putting the best interest of every patient first.
[00:23:23] If any of our listeners are interested in learning more about the peri- and post-approval studies and real-world evidence solutions at PPD, a part of Thermo Fisher Scientific, you can visit us at www.ppd.com and click on the link to peri- and post-approval from our solutions menu in the top navigation bar.
[00:23:42] Until next time, this is Science with a Twist.