Chapters Transcript Keynote: Increasing IDEA (Inclusion, Diversity, Equity and Access) of Underrepresented Patients in Clinical Trials Course: Health Disparities in Obstetrics and Gynecology: Approaches to Understanding and Improving Care This topic is really near and dear to my heart because as you see it combines my two passions, which are clinical trials and um improving um diversity and equity. Uh, so, um, I also want to say that while I'm a GYN oncologist, I think what I'm gonna speak about today can is really applicable to all specialties and Within OBGYN but even within all of medicine, because these are, you know, um, things that are not unique just to cancer. Um, I think it's, these are my disclosures. They are really non-relevant um to this presentation, but I do a lot of clinical trial work. So today what I'd like to do is walk you through kind of um a brief history, uh, and then speak about diversity and why it's important, and then talk about drug development and disparity in clinical trials, um, and then delve a little bit into some of the molecular differences and how that can impact differences in efficacy. And then um you've already heard a lot about the determinants of health and the social determinants of health, um, but I'll, I'll kind of review it again, um, in, in how it impacts um access to clinical trials and then finally, um, address kind of what we're doing about um addressing improving um clinical trial enrollment of diverse and underrepresented patients. So I think um let's start with 1845. James Sims um was noted to begin experiments on slaves regarding the surgical management of vesicle vaginal fistulas. He ultimately performed more than 30 surgeries on black women, you know, and we have the names here, without anesthesia, without consent until he perfected those procedures. Horrifying, right? Um, he even documented several that nearly died due to unsafe surgical conditions and infections. Fast forward about 100 years later, 1932 Macon County, Alabama, where it's estimated that 82% of that population was black, the median income, $1 a day, um, and this is, this is where Tuskegee was born. They recruited black men without informed consent for free healthcare in return for participation. 36% of those residents had syphilis and 99% of the blacks were never treated. Men were falsely treated with aspirin, iron tonic, vitamins for their syphilis, and they were monitored for the sequelae of syphilis. They had unauthorized biopsies, blood draws, um, you know, all performed without appropriate consent. And even after the introduction of penicillin, um, in 1943, the study continued and didn't end until 1972, and there was no formal apology until 1997 by President Clinton. So this um really triggered what uh the nation for a formal review of human research, and that is when President Nixon signed in 1974 the National Research Act in order to develop guidelines for human research. And I think all of you are probably familiar with the Belmont report which um highlighted the three important ethical principles um with research respect for persons, beneficence, justice, and you know, and this was a really important. Um, report that, um, was utilized by the IRBs for consent, for assessment of risks and benefits and the selection of subjects. These are things that we are, um, really tasked to look at on a daily basis when we do clinical research. So why is why is diversity important? I think we would all agree that the world is changing, and if you look here, um, the um uh percentage of people in Greece, Sweden, Canada, and US say that over the past 20 years, the ethnic, religious and racial makeup of their country has become more diverse. And you can see this is the um Pew Research Center 2020 data. You can see that Europe and Asia were home to the most international migrants, and you can also see that um the international migrants made up um more than 20% um in Oceania, um, and India, uh, with 18 million migrants, um, was the top origin country. So what about the United States? So this graphic gives us a glimpse of the current diversity in this country. It utilizes the 2020 US Census data, and you can see here that 60% identify as white, 18% as Hispanic, 12% black, 6% Asian. Um, and then, uh, lower percentages of native Hawaiian, Pacific Islander, American Indian, and Alaskan Native, and I think what's important is, um, you can see here about 3% identify as multiple races, but that's going to, um, more than double by 2060. But even more important is that um you can see here that the percentage of non-white um individuals is going to be increasing and it will be greater than 50% by 2045 and maybe even sooner. So, What about clinical trials? Well, the generaliability, um, currently the approval of a medicine relies on the evidence from a sample of the overall target population, and that approach relies on the expectation that the data evaluated arises from a representative sample of the patient population. And so, um, in order for us, um, to really know that this medication, um, uh, can be utilized by the um entire population, this, this population must be representative. So what are the consequences of lack of representation? So it can compromise the generaliability of your research findings. It can lead to huge research um costs, hundreds of billions of dollars. Um, for instance, with diabetes, um, you know, there could be a loss of $5 trillion through 2050, and this could be related to morbidity, mortality, loss of work, heart disease is estimated to be $6 million and hypertension even more. In addition, lack of representation, it hinders innovation, new discoveries, um, and it also may lead to um lack of access to effective medical interventions. Um, for example, the HIV drug Dyscoy, um, females were excluded, so we have no idea if this drug was really even effective in this group of patients. And finally, the lack of representation actually exacerbates health disparities in already underrepresented populations. And this is particularly true of phase one studies. So if you don't include underrepresented patients in these early drug um trials, you may not see signals of efficacy, and they may never move on um to later phases. So I'm gonna talk a little bit more about this because I think um people underestimate that. Let's consider the population that we passionately take care of, um, female participation in clinical trials, um, from 2014 to 2021. Um, these are, um, a review of studies from the FDA and Women, while overall represented 51% of um the participants, the representation varied greatly, and when you look particularly at cardiovascular disease, the yellow and infectious disease, the green, they were less than 50%. And given that known health disparities and biologic considerations, it's really important to consider um sexual and gender minorities and include them in clinical trials and research. Um, they're more likely to experience violence trauma that is associated with the anxiety, depression, and suicide, and this population is also at greatest risk for other comorbid conditions like cardiovascular disease, MI, HIV. And what's shocking, in 2013, there were no reported transgender recruited studies. Additionally, the majority of clinical trial registries, like if you go on clinicaltrials.gov, they only list male, female, or all as gender options, and there's no absolutely no information on sexual orientation. So, um, kudos to PrideNet, which enrolled over 13,000, um, sexual and gender minority people, and this serves as a great network for researchers who can use existing data or even propose new studies um uh through the Prideett, allowing for interaction between um subjects and researchers. Well, when looking specifically at research, um, in obstetrics and gynecology, um, Steinberg at all reviewed, um, obstetric clinical trials from 2007 to 2020 for disparities in the United States. Only 11% of the over 1200 trials on clinicaltrials.gov actually reported race and ethnicity. And overall, while you do see that increasing over time, you can see here that Latinx, Asian and American Indian, Native Alaskan were underrepresented um when compared to um the uh population. What about in oncology? So study populations vary by institution and cancer type, but patients from minority racial and ethnic backgrounds are consistently underrepresented. Black patients, they represent 15% of people with cancer, but only 4 to 6% of trial participants, and Hispanics 13%, but again only 3 to 6% of trial participants and, you know, similar to, um, you know, the obstetric trials, less than a third of cancer trials actually reported on race and ethnicity data, and this underrepresentation is probably even more. And you know, this point about phase one trials is so important, you know, the phase 1 trials particularly do not represent the population with the greatest medical need. So when we look at race reporting and representation in clinical trials that led to drug approvals over a decade, you can see there were 230 trials and while and with 108 drugs approved and approvals increased over time, but less than 50% of these led to um approvals um. And in less than 50% of these trials that led to approvals even reported on non-white races. And then on the right here you see um compared to white patients, you know, um black patients and Hispanic patients were um significantly underrepresented relative to their proportion um in the US cancer population. So this study looked at disparity in phase 1 G1 oncology clinical trials, and you can see here these were 300 phase 1 trials over 1985 to 2018, and with the exception of cervical cancer, white patients represented the majority of. Patients in these phase one trials and then enrollment when you look here, enrollment of black patients was less than expected from disease incidents across disease sites ovary, endometrial, and cervical cancer and more importantly, none of the phase one trials met enrollment expectation of black participants. What about immunotherapy? So, um, a lot of you might have heard of immunotherapy. It, um, has been revolutionary in cancer treatment, you know, leading to cures, um, and so this this study looked at enrollment of black patients, um, in studies of gynecologic oncology and breast cancer. And you can see here that um you know, black women were disproportionately represented in trials across female malignancies, you know, an 11-fold to 32-fold lower in ovarian cancer. So again, really significant disparity in just the studies. So, um, you know, I put this slide in here because I was talking to some of my colleagues in Europe and they're like, oh, we don't have a problem with disparities or underrepresentation. So, um, so I think it's important to highlight this is a global problem. Um, from 2007 to 2022, um, about a quarter of all clinical trials in the UK even reported on race or ethnicity. So very similar to the US, and of those that did, only about 50%. Reported no Asian participation and 43% reported no black participation in their trials and then when they looked when we look at um cancer trials, phase two and three breast cancer trials conducted in Europe with at least 200/250 patients, um, they found that race and ethnicity of 10% was reported and of those that did include it, you found that black patients and Asian patients represented 1%, 3% identified as Hispanic or Latin. So, and then, you know, in Europe, their largest ethnic minority, the Roma, they were not even included or even mentioned in any of these studies. So in terms of, um, you know, I think we also have to talk about underrepresentation in low middle income countries. So by 2030, um, 3 quarters of cancer deaths will be in low or middle income countries, and that means 1 in 8 will have a cancer diagnosis in their lifetime. 1 in 8. So most of this increase is going to be from low middle income countries, 400% in the low middle income and 168% in the middle income, and these are due to the rising population, increased life expectancy, and growing urbanization. And then of all phase three trials of anti-cancer therapies, only 8% were initiated and conducted in low middle income countries and In addition, we know that racial and ethnic minority populations are underrepresented even in high income countries, in cancer trials, so this is just a huge problem. So why do we need inclusive participation? So to reflect the racial and ethnic diversity of the population expected to use the medicine, to understand the potential differences in safety and efficacy, and then to mitigate help mitigate racial and ethnic disparities in health outcomes, and then finally to promote equity and justice, but. And ASCO actually states that access to clinical trials is a critical component of high quality cancer care, so really, really important to be able to offer everybody clinical trials. It's access to new medications, um, so let's focus a little bit on endometrial cancer, um, and I'm just gonna use this as a model. So endometrial cancer um has rising incidence and mortality both in the US and in Europe. In the United States we are seeing a um. Increase in aggressive histologic subtypes as well as an increase in the obesity epidemic, so both of these are contributing um to the increasing incidence, but the mortality is probably related a lot to this um increase in um high risk histologic subtypes. And when you look at um outcomes, um, this was a really nice study that was published, um, you can see here that ovarian cancer mortality is going down and endometrial cancer in the red is actually increasing, and that increase is greatest in the non-Hispanic black population, and you can see here they have um twice, um the mortality as um white patients, and this was so much of a problem that got highlighted in the New York Times. These are, um, I put this up here because I think it's, it serves as a nice framework to think about um how we should be looking at um incidents prevalence, um, and probably the best way to think about, you know, what is the right proportion of patients to include in your trials is if you're looking at an early stage trial or um a, a newly diagnosed cancer that's early stage, you probably wanna think about. Incidents and mirror the incidents in terms of that group, but if you're thinking about um a late stage trial or a recurrent disease trial, then you really should be thinking about prevalence when you're trying to come up with your metrics on what you want to mirror for um appropriate underrepresentation. Uh, appropriate representation of underrepresented patients. So let's talk a little bit about molecular differences. Um, so this study is a nice example of um why it's, um, why you need inclusive research to um reveal potential variations in outcomes of subgroups. So Elanib, um. was used in um previously treated non-small cell lung cancer, and women of Asian descent had higher response rates than the overall trial population. And when they looked further, they found it was due to the this specific EGFR mutation that was more common in Asian women. And so without really identifying race or reporting it, you would never know this. So this is a um a study that um Doctor Olivia Lara who um did with me when she was a fellow here, she's now um an attending at UNC um she is giving me this manuscript, so hopefully you'll see it published soon. um but what we did was we looked at endometrial advanced and recurrent, um, endometrial cancer patients and. Um, we that had NGS testing, and what was really interesting is we found that when we um looked, um, we found that the black patients comprised 47% of uterine serous cancers, and they comprised 31% of carcinosarcomas and so these are the higher risk histologic subtypes that have worse outcomes when compared to your garden variety endometrioid um cancers, and they only represented 11% of those, the ones that do better. So then we went on to look at, so what mutations did we see in these patients, and we found a higher proportion of CCNE1 amplified in the uterine serous subset. Um, and then really when you broke it down, there were none in the white patients and 38% in black patients. And then when we looked at outcomes, we found that patients who had a CCNE amplification actually had worse outcomes, the blue, compared to Um, the red here. So really kind of shows you why the molecular, um, you know, uh, differences are important. Another study um that um we did with um my colleague Doctor Angelus Alvarez Secord at Duke was looking um at real world data from an endometrial cancer consortium, um, where this was over 800 patients with advanced and recurrent endometrial cancer across the nation, um, and what we found was, again, really interesting. Um, that black patients had, um, a, uh, lower proportion of the favorable mutations, the PI3 kinase, the P10, and the beta-catenin, and they had a higher proportion of the TP53, which portends a poorer prognosis. Um, in addition, MSI and DMMR, um, you know, the, the biomarkers that we use to select for immunotherapy were more common in white patients compared to black patients. Um, so again, really, these molecular differences are there and they are also important in terms of driving outcome in these patients. Um So, um, we know that we're gonna transition a little bit into disaggregation of race, um, and ethnicity. So we know that not all Asians are the same, yet they're all aggregated together when we report it. So you can see how many different types of Asians there are. Um, and in our study we grouped these into East Asian, South Asian, Southeast Asian, and then, um, Um, Pacific Islander. And so what we found that was in in endometrial cancer, we found that um the um uh uh the Pacific Islander subgroup did had the worst prognosis, and it was very similar to that of the non-Hispanic black race. And we also found that the South Asians did the best, and this was controlled for demographic, stage, histology, and treatment, and this. work that Sarah Lee, our senior fellow, worked really hard on and really spearheaded, so I'm really proud of her, but, um, you know, it really is important to disaggregate race because you can see here that there are differences and, and we're going to need to know these differences so we can tailor treatment resources. So this other study that also is really interesting, um, this was done by one of my colleagues, John Chan and and his trainee, um, Doctor Reddy, um, and what he did was he disaggregated Hispanic um ethnicity, um, and so he looked at um the United States um Cancer Statistics database, the NCDB, and the World Population Review. And he looked at cancer um trends by demographic characteristics, histologic subtypes, obesity rates, and, you know, um, among Mexicans, um, South Central Americans, Puerto Ricans, Cubans, and Dominicans, and um it, it turned out that Dominicans had the greatest proportion of um uterine cancer that were more advanced and had higher risk histologic subtypes, and this could be because of um They could be of the Afro, um, uh, more of the Afro-Caribbean descendants, um, kind of the same thing that we see in the black population where we have those higher risk histologic subtypes. And then they also found, um, so that was nice because they were, were able to use the world population um review data and get obesity rates and, and they found that um Puerto Ricans, um, actually had the um highest endometrioid, the ones that are estrogen driven. Um, and, and you can see here on the right, um, they had very high obesity rates and they had the highest, um, proportion of these, um, endometrioid adenocarcinomas. So again showing you why it's important to kind of, um, disaggregate, um, uh, Hispanic ethnicity. So we've talked a lot about kind of. Issues, um, and, and, you know, uh, but I really now want to focus on barriers, um, to, um, increasing, um, diversity and equity, um, as well as um some of the social determinants and how they come into play. So. Barriers to achieving in uh in clinical trials, so we can break them down into these four buckets, um, clinician, patient, institution, and trial barriers. In terms of the clinician barriers, um, you know, there are a lot of implicit biases. There is, um, the belief that minority patients won't travel or won't comply with um trial protocols, um. In addition, clinicians are limited with their time. We're all, um, you know, we all have to meet our RVU targets, we have to see, you know, X number of patients. So really to try to think about, oh, what trial is this patient eligible for, it becomes, you know, difficult. Patient barriers, so limited knowledge, um, financial barriers, uh, you know, lack of access to transportation, food insecurity, distrust, um, given some of the historic atrocities that we, um, you know, briefly glanced on earlier, and then language barriers. In terms of institutional barriers, um, access to clinical, um, trials, having the right trials open, you know, for the patients that you serve, but sometimes that's a big problem. Um, in addition, there's been data about diversity of research staff, so, um, it's really hard to sell, um, a clinical trial to someone, uh, as given the fact that you are using a novel treatment. There are adverse events, um, they don't speak the language, and so studies have shown that if you have um people that look like you that explain these things to you, um, they can relate from a cultural, um, uh, standpoint and are more open to clinical trial participation. Um, but I also want to point out that, um, you know, and this goes in it. You know, in line with the the physician bias that most patients if actually asked to participate in a clinical trial, will actually go on, and that percentage is like 70%. So ASCO actually has um partnered with um ACCC um and they have come up with a just ask training, um, which is really to try to remove some of that clinician bias and really just ask patients about clinical trials and participation. Um, and then trial barriers. So we all know that clinical trials can be very onerous on patients. Sometimes they have very restrictive eligibility criteria. And that becomes really important because these are the patients that we know black patients have a higher incidence of diabetes, hypertension, their creatinine clearances are gonna be lower. And so um we have to keep that in mind as we're designing trials. So unless that is important to the medicine you're studying, don't make it a restrictive eligibility criteria, um. There's actually a wonderful document um that um it's called the AsO Friends document that actually, you know, um, points out that you really need to be thoughtful so you do not limit eligibility eligibility of these um patients. And then finally, um, numerous visits, right? So there's all these safety visits, there's PKs, so we have to be thoughtful about that. Um, one, can we, um. decentralize this? Can we do some of this through telehealth? Can we um cut down the number of visits that they have? Can they get local labs? Do they have to schlep into the city, for instance, if they're out in Brooklyn? So all of these are important considerations. So I think um we'll move on to the determinants of health and the social determinants. So I think the determinants of health can be best summed up in the context of 10% being driven by genes and biology, 10% by physical environment, 10 only 10% clinical care guys, 30% health behaviors, and 40% your social determinants of health. Um, so, you know. This is so important that um the ICH actually um in their guideline, they advocate for both the intrinsic as well as all these extrinsic factors that are that are important to be taken into account early in drug development. And we talked a lot about social determinants of health, so I don't want to belabor it, but it's really just the conditions into which you're born, grow, live, work, age in, and the and they're the fundamental drivers of cancer outcomes, um, and they can lead to lower screening rates as we've heard, later stages of diagnosis, higher rehospitalization rates and higher mortality. And but how do they affect clinical trial participation? So, you know, in terms of the economic, um, you know, the explicit costs are rare, like, but the implicit costs are real to these patients. Transportation, how are they going to get back and forth to these like numerous visits that you're expecting them to do? Childcare, right? They need someone to watch their kid, um, parking, loss of income from missing work, they need their paycheck to put food on the table. So these are all very overwhelming to patients um without economic resources. In addition, you know, we talked a lot about this um the neighborhood and the environment. So, um, of course the lack of transportation, but what about access to medical centers, affordable childcare, the community outreach from researchers, um, all of these can contribute to disparities in um clinical trial participation. And then education, we know that there's lower health literacy, um, so I mean it's hard enough for them to understand their diagnosis, let let alone trying to explain a research um trial and go through a 20 page informed consent. So, you know, they are often complex, difficult to interpret and comprehend. So I think the onus is on us to really simplify that message, um, and the onus is also on us to simplify those consent forms. Um, and they're supposed to be at the 8th grade level, but they never are. And then community and social context, so really exposure to discrimination makes you not want to reach out to the broader society and get, you know, uh care or enroll in trials and the mistrust that develops from that. Um, and then finally, um, we talked about this already access to care, poor quality of care, and low insurance coverage. That's another reason that um patients um cannot participate in research studies. And you know, um, this is a study that Michelle Lightfoot and Sarah Lee, um, did, and I'll just briefly summarize it. It really is demographic reporting and language exclusion and GY and oncology trials. They looked at endometrial cancer trials. There were 260 of them. Um, 27 or 10%, 1 in 10 endometrial cancers over the last three decades did not allow non-English speakers to enroll in clinical trials. And then again to reiterate this point, less than, you know, um, only more than 40% of um trials published endometrial cancer trials did not include, um, race and ethnicity, um, in, in, in this, um, evaluation. So, um, you know, so what do we do about all this? So ASCO ACCC, um, put out a nice joint statement, um, which I think is really well done. They outlined six key recommendations to increase racial and ethnic diversity in cancer trials, but as I said, I think these are applicable, um, and these recommendations apply to trial sponsors, investigators, organizational leadership, clinical and research teams. And I want to just briefly, I'm gonna go through, I won't spend too much time, but I think they're important. Um, the first is to ensure that all patients have opportunities to participate in trials. So that means we have to commit to this, right? We have to have a clear mission, we have to measure the people that we screen, enroll, and the barriers that we encounter. Um, we have to report these metrics, and then we have to like figure out ways um to mitigate the issues if once we uncover them. The other thing is we have to screen every patient. So again, this removes any of those implicit biases we have too. So we have to develop standard protocols to screen every patient, and this is a true challenge because we have very little manpower. I mean, you know, we barely have manpower to Have to enroll patients and keep them on trial. So to have a pre-screener to identify patients is really difficult. So I'm gonna talk a little bit later, but you know this is where we can utilize the AI and there are some really cool things happening in this arena, um. We also need to collect and analyze um the demographics, again, as I said, screening, participations, and the reasons for not qualifying or or staying on trial. And then we have to design trials with this in mind. So one, we have to decrease overly restrictive eligibility criteria, and then we have to involve patients. I mean, this is a conversation that we had earlier today, like involve patients in, you know, in the study design and so we're starting to do that now. We're starting to put them on our PRMC so that they can review and comment on the studies that are moving through. um, so I think this is really important. And then in terms of um increasing the diversity of trials at your site, so um I talked about this earlier open trials that are most relevant to the population that you care for and make sure you have trials to address the diverse population, um, especially because they have poorer health outcomes, and then, um, you know, make sure that you um develop relationships between small and large research sites, um. And then broaden your, this is more for um sponsors, but really making sure that they, you know, fork out the money to um include more community sites which, you know, may be harder for them to get on. Um, and then form long standing partnerships with communities. So, um, these partnerships should happen at all trial stages, so, um, increase the collaboration with community health workers, community leaders, patient advocates, you know, participate in community advisory boards, and then share the results. So, um, share the results with the patients but also with the communities that you engage with. We often forget, we do the research and then we get this great data, but then we don't tell our patients. So we have to tell our patients what the study showed, thank them for their participation. Um, and then we have to develop education resources, um, with partners, so making sure that they're culturally sensitive is really important. So not having, you know, um, Uh, a pamphlet or a video on clinical trials only in English. So, let's put them out in other languages with, you know, other, um, races and ethnicities reflected on those, so people can connect and really, really understand what we're trying to do. Um, require all research members to complete training in cross cultural competencies, bias, and building trust, um, so really having, um, you know, doing these but also evaluating the successes and areas for improvement, um, we're in, you know, in our clinical trials office we're actually going to mandate that everyone does the EO just ask training. Um, and then, you know, uh, we're gonna also incorporate a few few other measures because I think every investigator should undergo that training, um, because it's very eye-opening. Invest in programs to increase idea by all stakeholders, so really you need money to make this happen. So you need to have um funding for travel, parking, accommodation, um, and then patient education, right? You need, you need trial consents, you know, translated into other languages, ideally before you start, as well as PROs like patient reported outcomes, they shouldn't just be in English, they should be translated. Um, and we need to understand how it affects all people. Um, so all of these things require, um, resources, and so the onus is on us when we're, you know, when you're interacting with sponsors to do a trial, make sure that they're doing these things. Um, build and maintain a diverse workforce, um, you know, obviously I think that's self-explanatory, but that's across, you know, trial sponsors, healthcare organization, research sites, um, and we talked about that earlier today as well. And then, um, yeah, having. The infrastructure to to meet the needs and here I think is really critical is the clinical trial navigators which um there is there are ample data to suggest um how clinical trial navigators um really improve um enrollment as well as retention on clinical trials. And then collecting and publishing so we I highlighted the problem, right? We don't do this so um really to make sure in all your publications that you include these, um, and then finally share strategies that are successful and share um uh also publish data on effectiveness and so what's happening, you know, um on a broader level so. In the US, the FDA has issued a guidance on diversity plans. Um, the WHO has, um, a guidance on underrepresented populations in clinical trials. The Australian Clinical Trials Alliance has provided recommendations. Health Canada has a draft guidance, um, the New England Journal has some requirements, and then finally, um, the GOG, and I'm gonna just run through this quickly. So these are the FDA guidance on diversity plans to improve enrollment of um participants from underrepresented racial and ethnic populations. They are now saying any drug that you are going to apply for a marketing submission with the BLA, you have to have a diversity plan, any phase 3 trial, so they have to have diverse groups to be part of the study to evaluate whether it's safe and effective, um, and they, and to know whether there are differing side effects between one group or the other. Um, in addition, sponsors need to dis uh, to present, um, uh, and, and report effectiveness and safety data by gender, age, and ethnic group, um, and any modifications of dose or dose intervals needed for specific subgroups, um, and then there they need to have in their plan, they need to put in the strategy, how are you going to enroll a diverse population and how is it going to reflect the population that you are studying? Um, and then finally, um, yeah, this, as I, I already mentioned this, that they need, um, they need to, this is a requirement. So the WHO draft guidance um for best practices for clinical trials, um, their key message is that we need to have strenuous efforts to be able to recruit diverse populations into clinical trials and especially in low middle income and resource limited um settings and children and infants, women, elderly, um, all need to be those with comorbidities and disabilities, um, and people of racial or ethnic backgrounds. So, um. You know, all people should be afforded the opportunity to be included in research, and ESO really strengthened that, stressing that the trial population should be really representative of the real world. Um, In Australia, they came up with the summary of recommendations and you'll see a lot of similarities, which is a good thing, um, that community led engagement, um there should be community led engagement and involvement, um, that you should embed learning and building capability to support um uh culturally and linguistically diverse, um, people, and then finally, um, really strengthening their clinical trial system to promote inclusion um of diverse um people. Health Canada's draft guidance um is a document for sponsors who are going to apply to market their drug for human use, and they want they really um are promoting disaggregated data and subgroup analysis to look for differences in efficacy and safety between clinically relevant and um different prognostic subgroups and. And they want to increase the transparency um in terms of race and ethnicity for, for um their um products. So, As I said, the New England Journal um is improving, um, as well, um, they now have requirements um to really make sure that um they um look at a sex and gender, age, race, ethnic, um, race and ethnic group, and any other considerations as well as the overall um representativeness of this trial. So all really important. And then finally I'm gonna end with um what are we doing in the GOG um so we're addressing it from four different aspects education access, research and policy and in terms of the education front, so we have um partnered with SGO, which is the Society of Gynecologic oncology, and we have um now published a joint um paper, um, which will, which serves kind of as a roadmap, um, to how we can address these issues. Um, in addition, um. I represented the GOG Foundation as the diversity expert at our GC at first, um, endometrial consensus conference, and now IDEA will be included in a consensus paper that was accepted to Lancet and it's gonna be incorporated into all future endometrial cancer trials globally. Um, which I'm really happy about, um, given that they didn't think it was a problem, um, and then in, uh, this past winter we had, um, at our NRG, um, meeting we had an educational symposium that, you know, as I said earlier, um, that we had over 230 people, we had, um, it was really great we had Nadine Barrett, um, who really was the who spearheaded the um As or Just Ask program come and speak and. Um, and, and it was, um, uh, really a workshop where we address these issues in, in detail, um, and then, um, we are putting together some idea educational modules, um, about commitment, um, community engagement study planning, study conduct, workforce development, accountability, advocacy, um, and that's in progress right now. In terms of access, um, so we really, um, in terms of really increasing, um, and removing um social and financial barriers, so we, um, advocate all our GOG partners trial budgets include financial compensation to address these um uh social determinants of health like. Transportation, you know, food, whatever it may be, childcare, um, in addition, we are, um, we have an idea call with all our sponsors that we work with, um, really educating them, um, on the importance of not um excluding patients, um. And we all of our investigational um initiated trials should also be doing this, and we're putting in some processes in our own CTO to also be looking at this, um, and we probably should be doing it in OBGYN as well, um. In addition, um, we are including, we're, um, really trying to include more community sites to increase um trial access to diverse patient populations, and currently we're actively collecting data on our ongoing trials to evaluate sites and come up with diversity metrics so we can make sure that the sites that we select, we will be able to enroll that diverse population, um, and then working with advocacy groups, um, and organizations to promote clinical trials in the community, so. I've worked with all of these groups, share, Icon, Clarity, see me, um, and it's really, I think, important to get out there and speak with the people in the community. Um, they need to hear why we do clinical trials. I mean, we change standards, you know, when we do clinical trials. That's, that's where, you know, our standard of care is determined and, and it's so important that we have, you know, patients from all different groups represented um in these trials, uh, and, and when you sit and talk to them they get it, uh, and so it's really important to be in the community and network with them. Um, in terms of research, um, So we are working, as I said, with sponsors on education. Also, um, we, I actually review these diversity plans, um, and make sure I hold them accountable. I make sure that they're putting in there like that they're gonna capture race, reporting of gender, make sure that they are setting their enrollment goals appropriately, making sure they've looked at. Incidents prevalence, um, and, um, and then, you know, it's important to also have interim monitoring of goals and you know what, we're actually seeing improvements. So our first, um, one of our recent endometrial cancer trials which looked at lenvatinib and pembrolizumab, and I wanna say that was in um 2019 or 2018 maybe, um, 4% black patients, that's it, 4%, OK? Um, and this is a treatment that's really important, right, for black patients. We've just shown that they have twice the mortality, um, but you know, with GYO18 we've seen about a quarter of those patients, um, are of underrepresented, um, uh, backgrounds, um, and same with Ruby, we had a uh a greater proportion. Um, keynote A18 is a large phase 3 cervical cancer trial that looked at immunotherapy in the front line, um. And over 50% of those patients were um non-white, so that's, so I think we're we're starting and we're seeing these small improvements and, and I think we have to just keep doing it. Um, we're also implementing an idea study chair on all of our, um, trials, uh, especially the phase 3 trials, um, so there are gonna be the champions for making sure we have diverse patient accrual, and, um, as I said, all phase 3 IITs have diversity plans, um, and I think, you know, the onus is on us to make sure that the IITs we do within our institutions also have, um, diversity plans. In terms of policy, um, we don't do, um, we can't directly do, um, uh, advocacy work, um, but we partner with SGO, um, SGO had a fly-in, they advocated this past year for the diverse Trials Act, um. There are other things that are going on. The Fedora that was signed into law in 2022 that has provisions for clinical trial diversity and modernization really with um making sure that we do those diversity plans to try to decentralize trials and to streamline trials and then the White House Office of Science and Technology is leading a whole of government approach to this to improve clinical trial capacity to enable more diverse um participation. Um, and so we're gonna continue to work with SGO, with ASCO, with AACI, which is, um, a clinical trials group, um, and, and continue to advocate. Um, I just, you know, this was really cool because navigators are now CMS approved, um, and they work for, um, you know, um, principal illness navigation which cancer falls into, as well as other high risk conditions. Um, so I think we should really be including these navigators cause they improve outcomes, um. And this only happened about, I want to say, we learned of this in end of February. So this just happened and we're we're looking into how to implement navigators um within our clinical trials infrastructure. So, like, um, like others, I don't like leaving with just problems, but I like solutions, and especially as a surgeon who likes to cut things up and fix things, I like solutions. So, um, so this, this is just like, you know, breaking it down, you know, what are the um barriers and what are the solutions. Um, it's not this simple, obviously, but it's, it's nice to have some framework. So in terms of the financial toxicity, making sure we have reimbursement vouchers for cost of travel, meals, child care, social services, um, cultural barriers, um, and you know, in terms of the social services too, I just, there are, you know, some new things that I've just learned, um, there's a company called Unitas, um, that really, um. Allows you to have patience, access all the services in the community. So, um, and what we're now looking at doing is getting, you know, sponsors to pay for this. If they want us to do this trial and they want diverse patients, like, let's help these patients. We don't have enough social services in in our clinics. We have one social worker and we have a lot of patients, and each one of these patients requires so much. So there's there's newer solutions that are out there and we need to be able to access these. Um, there are cultural barriers such as language and trust that we talked about, so really translating all those patient materials into multiple languages with appropriate cultural references, um, there are physician unconscious biases, you know, we talked about this, right? Um, really, um, the diverse workforce, the cultural humility training, the anti-racism, the unconscious bias training, um, there are the Asco Just Ask program. Um, and then reviewing, um, in terms of the inclusion criteria and comorbidities and organ dysfunction, um, just reviewing all these protocol inclusion and exclusion criteria, really identifying items that are not critical for trial and getting rid of them, um, and then really being mindful of these excessive visits, need for PKs and visits and seeing if some of these safety visits can just be done as telehealth. And then in terms of um site barriers, um, the lack of um uh sites um really engaging with more community cancer centers. Now this is like sounds great, it's not easy, this just in time activation where you can try to get like a site activated just in time so they can go on. Um, this is something we'd love to work towards, but it's this is not easy, um. And then they're also working with community cancer centers, um, so really making sure your community cancer centers understand what trials are open. So I often have these conversations with, you know, community centers in Brooklyn, so they know what trials we have open and they can send us patients, um. So, and then really identifying those sites with diverse populations, um, and then um this pre-screen, so really providing services for pre-screening. As I said, it's um really hard to use, um, you know, a human um time to do this. It it takes a lot of time. Um, but there are, you know, some epic-based, um, AI algorithms. They're not perfect, but we're gonna, we're actually, I've been interviewing these companies for about a year and a half now, and we finally settled on one that we're going to move forward with, um, here at NYU and um we'll see how it works, but it's a start, and, um, and then, you know, when you're doing sponsored studies, like, you know, use your voice and ask for these supports cause they're the they're willing to provide it, so. Um, you know, there are, you know, um, rewire or Vostar or additional resources that you can ask sponsors to provide you, so you can do some of this pre-screening. And so this is just our um paper that we published the joint paper um looking as, you know, to really just serve as a a a little bit of a roadmap. Um this is our website and it has um it actually has our winter energy educational symposium on there as well as our, um, the idea modules be going up. And then this is our GCIG global brainstorming where we were able to come together to really um propose global solutions and tackle global problems and come up right we talked about why the low middle income countries are so important in this um really my plug is really we do need to to make um inroads in this area so important. Um, I wanna thank my NYU family here. Um, this is the GY Oncology group, um, who've been so supportive in allowing me to do all this work, um, and this is my, um, clinical trials, um, group, and I, I like, I just wanna use this, like I wanna show you, like this is the diverse group that I have. And yes, I am lucky that I'm in New York and I'm able to recruit all these, um, you know, people of diverse backgrounds, but Um, I think if you, if you can, you really should try because it does help. If you can't, there's, you know, I think, um, really cultural humility training and really trying to understand people and where they're coming from, listening to kind of their barriers, I think are all really important. And I think with that, I'm done. Published May 3, 2024 Created by Related Presenters Bhavana Pothuri, MD View full profile
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