In this episode of The Scope of Things, Deb Borfitz speaks with Murray Aitken, Executive Director of the IQVIA Institute, about diversity in clinical development, DEI methods that are and are not working, and the impact diversity has on clinical trials. Aitken also discusses FDA-issued policies to advance diversity and efforts to reduce disparities between subpopulations. He also talks about factors that contribute to those disparities, such as socio-economic backgrounds, genetics, and trust in the system. Finally, he delves into the importance of having diverse groups of participants—particularly Black and Hispanic Americans—in clinical trials to ensure that patients receive the best treatment options and healthcare access.
Links from this episode:
Clinical Research News
Scope Summit
IQVIA Institute
In this episode of The Scope of Things, Deb Borfitz speaks with Murray Aitken, Executive Director of the IQVIA Institute, about diversity in clinical development, DEI methods that are and are not working, and the impact diversity has on clinical trials. Aitken also discusses FDA-issued policies to advance diversity and efforts to reduce disparities between subpopulations. He also talks about factors that contribute to those disparities, such as socio-economic backgrounds, genetics, and trust in the system. Finally, he delves into the importance of having diverse groups of participants—particularly Black and Hispanic Americans—in clinical trials to ensure that patients receive the best treatment options and healthcare access.
Links from this episode:
Clinical Research News
Scope Summit
IQVIA Institute
Hello and thanks for joining us for this month's edition of The Scope of Things, a no-nonsense look at the realities and enigmas of clinical research based on those closest to the action who aim for great and, if need be, are willing to shake things up. I'm Deborah Borffitz, senior Science Writer for Clinical Research News. In today's episode, i'll be speaking with Murray Aitken, executive Director of the Icubia Institute for Human Data Science, about what's working and what's not when it comes to advancing diversity in clinical development, in particular, the participation of Black and Hispanic Americans. Welcome to the show, murray.
Speaker 2:Thanks, deborah, great to be with you.
Speaker 1:Okay, at this point in time, i cannot imagine there is one company out there that doesn't have diversity, equity and inclusion, dei, on their radar, if not a fully developed strategic plan for erasing the disparities once and for all. But, as you and I both know, not a lot has changed after many decades of effort, so is this in some sense just politically correct lip service being paid to a serious and intractable problem?
Speaker 2:Well, you start with a good question. I mean, the short answer would be no, it's not just lip service. I think we've definitely turned a corner on this issue since the pandemic highlighted the stark disparities in COVID-19 outcomes among different racial and ethnic groups. We also had the death of George Floyd in 2020. That, i think, was a turning point for a much greater focus on the issues of race and racism in this country. We also turned a corner at the end of last year with the passage of the so-called Fedora Act, which includes the requirement for diversity action plans to be developed and submitted and approved by FDA in advance of pivotal trials starting. So that's a requirement that definitely puts some teeth into the guidance that had previously been issued by FDA, and it also is a step up from the reporting requirements that came into effect a few years earlier. So you add all that together and I would say we've definitely had a sort of a gathering of steam, a collective focus, and I don't see it letting up. I would say we also see real change happening. In addition to the public commitments and statements, on the ground, we're seeing things play out differently and I'm sure we'll get to talk about that as we go through. So, yes, yes, so things are changing, but it does take time And, to your point, we've been at some version of this for a few decades and the reported progress whether it be through the from the FDA snapshots report that they publish annually or research that we've done at the Icubia Institute on the data that's being uploaded to clinicaltrialsgov that progress shows it's been relatively limited and in some sense it's actually going backwards.
Speaker 2:So we reported in our recent research that for phase two and three completed trials, black or African American inclusion was at about 80 to 90% of the US demographic level in the early part of last decade, but it's fallen since 2016 and was only at about 50% of the US population level in 2028.
Speaker 2:And for Hispanics, it's been sort of in the 40 to 50% range of the US Hispanic demographic level over the entire last decade. So we're not seeing in the data that is being reported for completed trials. It's a bit of a lagging indicator, but we're not seeing strong signs of progress, at least through that lens. So I think it's fair to say there's been more public commitments and public statements of intent than there has been documented progress. Again, at least in trials that have been completed and where the population demographics have been uploaded to CTgov as required. But we're optimistic that we're about to see a turning point that will see the results of the efforts that have been going on and the commitments that have been made over the past sort of two to three years and that that will show up in the reported metrics. But it's not showing up yet.
Speaker 1:Right. So we'll remain hopeful and waiting to see the numbers move. But I want to back up just a second because, despite all the talk about diversity, equity and inclusion, it may not be obvious to everyone out there why it matters so much. It might be obvious to you and me, But so let's just spend a minute there, if you would, Marie. Why does it matter?
Speaker 2:Right. So I think it is important to keep our eye on the ultimate prize, which we think of as being a reduction in disparities in outcomes among different subpopulations in this country. So you know we look at the differences in mortality. You know we see it in mortality rates among black African Americans that are 20 to 90 percent higher than for the overall population, depending on the disease much higher mortality for patients with diabetes, for patients with cancer, with cardiovascular disease, as well as with COVID-19. So we know that there are real and meaningful significant disparities in those outcomes. We know there's a lot of factors that contribute to those differences and outcomes. There's some genetic or biological differences, there's healthcare service access differences, there's socioeconomic status differences, there's social equity and trust in the system issues. So there's a number of reasons for those disparities and outcomes. But we do know that participation in clinical trials, in clinical development programs, is one of those factors And for those of us with a focus in this area, we have to sort of step up to our responsibility to do what we can to contribute to the reduction in those disparities And that will bring direct, but also maybe indirect benefits to patients who are affected by these disparities.
Speaker 2:And what I mean by that is, you know there's a broader consensus that confirmatory trials should be conducted with subjects who are representative of the disease being treated. But we can imagine that bringing those subjects into the trial will have a downstream benefit of more of those subjects or people from that subpopulation ultimately being treated with the drug that is undergoing the trial, because the participation of subpopulations in those trials brings greater confidence in the appropriateness of the particular drug in treating the subpopulation that's represented in the trial. So that is sort of a we actually think is a more significant and bigger impact that we can imagine It happens downstream. But it is another reason why this is such an important topic And, again in the context, that our ultimate goal here is to reduce these disparities in health outcomes.
Speaker 1:Yeah, well put, well put, And talking about the responsibility that we have as an industry, we can do what we can do. we contribute to a bigger effort that's a bunch bigger than industry itself. for sure And Ikevia's report on the topic issued last fall you had referenced the point is made that it takes everyone in the clinical development ecosystem to move the needle. I'm wondering if part of the problem is that the commitment level of different stakeholder groups is uneven. Besides patient advocacy groups that have historically pushed the agenda on diversity and staged some pretty major trial awareness campaigns, and these multiple cycles of legislation on this front in Congress, who is truly rising up to lead the charge in a meaningful way?
Speaker 2:Well, i would draw attention to the role that sites play in this clinical trial ecosystem. I think they really have a very critical role to play in the research that we did, where we were looking at again so who's really stepping up, as you say, in a meaningful way. In a meaningful way, we highlighted a couple of sites that we interviewed and met with. For example, we highlighted the Monroe Biomedical Research as an example of a site that responded to the call to include more Black and African American patients in trials. It's seen that its patient-centered approach results in enrollment rates that are well above that of the surrounding population. And when we talk to Ben Kasai, one of the co-founders, he attributes those results to what he calls, or we would call, an organically grown, patient-oriented staff in a thoughtfully designed trial environment. So what does that mean? It means that when he talks about a patient's trust stemming from the experience that they have with the site's study team, it's important that the patient sees a team that is passionate about what they're doing, because that helps the patient perhaps expect the same in turn. But also, if a patient observes a racially diverse staff who are cooperating, respecting one another as they work together, then patients of color may well expect the same treatment as a result, and that helps to contribute to this establishment of trust which is so much at the core of the broader issue and where the site has such a critical role to play. So, you know, ben talks about bringing in staff to his medical center who are not only representative of the local community but who also share a passion for patient care, because he believes that's what comes through when the staff interact with potential study participants, and that's really sort of where the emphasis is placed. So you know, that to me is just, you know, an example. It's a good example of a site that is stepping up to the challenge and leading the way forward.
Speaker 2:We also, i think it's fair to say, see sponsors who are adapting their approach, whether it be in the design of the trial protocol or the consideration of the inclusion and exclusion criteria, which we know have an impact on enrollment, the selection of sites, culturally tailored outreach approaches I mean these sorts of things. We do see many of the sponsors again stepping up, adapting their approach, and I think they're also more likely to be tracking enrollment and dynamically adjusting their approaches, you know, having dashboards that provide real time tracking and can therefore enable them to adjust screening and randomization activities. A lot of this, by the way, you know, really came to the fore in the context of the COVID-19 trials, where the sponsors of those trials again were very much aware of the importance of having representative trial populations and actually achieving results by doing some of these things, which are now more likely to be implemented in other trials. So, you know, those are things that we see. You know stakeholders stepping up to.
Speaker 2:That being said, there's still some cross currents, mostly around who's paying for it And what are payers going to reimburse, what are they willing to reimburse, particularly around the standard of care, you know, treatments and so on. There can also be, you know again, conflicts between the investment that may be needed in training site staff, in creating the infrastructure, but and again, but who's going to pay for that? And so you know it's not as if there are no tensions in the system. There are even. At the same time, we recognize that you know we all need to be in this together in order to move things forward.
Speaker 1:Yeah, yeah, and while efforts to improve diversity in clinical trials, you know, the efforts are all focused primarily on race and ethnicity. Other dimensions matter too, as you well know, and in any case, as we just talked about, ultimately differences in patient outcomes is what really matters, and that's a much bigger nut to crack. How do we keep our eye on the bigger picture here and not miss the forest for the trees, so to speak?
Speaker 2:Yeah. So I think there's a couple of important things here. One is, yes, the issue of disparities and outcomes can be looked at through the lens of race and ethnicity, and that's an important lens to look through. But there are other lenses to look at as well. Gender is one, and I do notice a lot more attention being given to representation of women in trials or therapeutics that affect women differentially or where women may have a differential response to the therapeutic, and there's a lot more to be done on that dimension.
Speaker 2:I think age is the other one, where over 65-year-olds do get a lot of medicines that have only been filed on patients under the age of 65.
Speaker 2:So I think we're going to see some movement in order for the demographics, the age demographics, to be more representative as well. And then there's the bigger, broader and more difficult socioeconomic status as a dimension of disparities in outcomes and therefore a dimension that should be considered in a clinical trial design. I think, if you actually read, though, the diversity action plans and the draft guidance already out from the FDA, that is requiring all relevant factors to be considered And for that consideration to be documented in the diversity action plan that gets submitted, so we are going to be getting a lot more focus in these other dimensions, at the same time, that race and ethnicity remains probably in the foreground, at least for some time. So it is a bigger issue. There are many dimensions to it And I think fundamentally it comes back to designing and executing clinical trials that include study participants who are representative of the patients who will ultimately be treated potentially with that medication, and that's the core of the issue, and we've got a long ways to go to really get to that level.
Speaker 1:Yep, but we're having a conversation and that's where things start changing. We were talking a minute ago about just the cost of all of this, and so I was going to ask next about sort of the business case for sponsors spending the time and money on improving diversity and trials. Now, obviously, the reduced regulatory risk has to be part of that business case. I'm sure there's more to it And I'm sure you speak to sponsors about this as well. What is your pitch to them about what the business case should be, if they don't already know?
Speaker 2:Yeah. So I think even the quote business case, I think, starts with an acknowledgement that for companies that are operating in the healthcare system and the nature of the social contract that exists between pharmaceutical manufacturers and the rest of society, addressing these issues is the right thing to do. So, again, it may not be considered a business rationale but it is a part of that social contract which does in fact underpin the business environment that companies operate in. But yes, you're right, It's also useful to have a business case. I think the FDA requirement for diversity action plans again puts teeth into this.
Speaker 2:A rejected plan by the FDA will delay a trial start. These plans will have to be they'll be signed off or not within 60 days of submission, but that's a real timeline that could ultimately delay the trials. We've also seen the regulator of the FDA issue complete response letters and in some cases require post-approval commitments linked to the lack of diversity in a pivotal trial. So that's a real consequence that we see. But I think this other issue I touched on earlier, this linkage between trial diversity levels and the subsequent use of new medicines once approved, is another way to think about the business case. So we hear about hesitancy by patients, by clinicians in using drugs that have been approved by the FDA but have not had representative participants in the trial, So that can have a real impact on the uptake of new medicines. That has a business consequence.
Speaker 1:Long term.
Speaker 2:And we've longed absolutely long term And we think that that explanation, if you like, of the downstream impact of greater representation in trials is one that hasn't been fully explored. But we think that is an important one to actually better understand and indeed may form part of the so-called business case.
Speaker 1:And I know that you mentioned a great site, example of this site stepping up to the plate in this arena. But is there any sites collaborating actively with study sponsors on this front in any meaningful way, or anything with a proven track record we can talk about and point to as a model for others to follow?
Speaker 2:Well, i think every sponsor has their examples of sites that they are investing in and collaborating with in order to achieve high levels of representation in their trials. Again, that investment can be financial. So that comes, as we discussed earlier, with its sprinkles. I think the other point is that we still haven't gotten over this issue that one sponsor that has one trial, or even a few trials, is unlikely to be able to justify the investment in setting up an entire site or serial or site network to conduct the trial, because at the end of that trial They're going to go away and they may not be back for several years with another drug candidate where that site or those sites would be optimal.
Speaker 2:It's a lumpy business. I think we ran a or hosted a symposium in Chicago at ASCO, really talking about this issue that if actually some of the sponsors got together they could collectively be able to do more in supporting site development, particularly community sites. That's really what we're talking about rather than the academic centers, because among them they'll have more, they're more likely to have an ongoing stream of trial activity, more so than any one will have on their own. So I think that's one area where we've still got some work to do in terms of how that relationship between sponsors and sites evolve.
Speaker 1:Yeah, yeah, diversity. Data collection itself is relatively new, and so even having a good handle on how we're doing is a big deal to even get to that And maybe you can talk a little bit here about a QVS analysis on this front what you've been learning about what's how we're doing now, i guess, and how much and where specifically we need to improve.
Speaker 2:So there's definitely a few things that we've come across as we've been looking at this more intently over the last year or so. One is the well, the FDA snapshots report. Let's start there. That's something that was mandated by Congress as an annual report to show the race and ethnic makeup of participants in the pivotal trials for approved drugs. That's somewhat helpful, but it has gotten difficult to interpret, i would say, in part because it doesn't distinguish global trials from US-only trials. So the reality is a large number of clinical trials are conducted in more than one country and more than the US. That being said, actually we were surprised about 40% of trials have only sites in the US, so they are what we call US-only sites. By the way, they're not enrolling populations representative of the black, african American or Hispanic populations either, but they're certainly doing better than the trials that are spread across multiple countries.
Speaker 2:And I think one of the gray areas in all of this is how can a global trial be considered representative of the American population, especially if the US sites are a very small percentage of the total And no one's?
Speaker 2:there's no black or white answer to that, but and again, the snapshots report sort of ignores that issue, we would say, and we think actually the snapshots report would be much more helpful In addition to giving the overall sort of trial composition showed for US sites of that trial, what was the race, ethnicity composition and then for the ex-US site, what was it.
Speaker 2:I think that would help clarify a little bit what sponsors are doing, at least with the sites that are based in the US.
Speaker 2:We know that the reporting that is done in the metrics that we can measure only tells a part of the story, but it is something tangible, it is something that we can track over time in an effort to know whether in fact we're getting better or we're getting worse. Of course it is important we would say that the sort of comparator that is being used when looking at trial participation is the prevalence or incidence or prevalence of the disease being studied in the population, so not the sort of total US demographic share of the population, but rather for that disease, because we know that triple negative breast cancer affects African American women disproportionately than compared to white women, or sickle cell disease clearly is disproportionately affecting black Americans and so on. So we've got to be careful about the comparator that gets used And in fact to have the epidemiology data to know what that comparator is, and there's another whole set of issues around that that I don't think we have time for today but, i, just put out there as well.
Speaker 1:It sounds very tricky. Obviously, companies can improve what they don't measure. Which brings us to IQVIA's inclusivity quotient. It's a tool for quantifying how much a clinical trial departs from rural world patient distribution by education, provides a comparison across trials and drugs and identifies the factors contributing to the deviation. Please talk about that, tell us listeners. When was it developed? How much uptake has it had And, most importantly, if the output is changing the way companies operate, or is it too soon to say?
Speaker 2:So it's a tool that our data scientists developed over the last two to three years as a way to have a more meaningful way of measuring the representativeness of a clinical trial, And it does a couple of things well. One is it brings it deliberately brings in the epidemiology data for the underlying condition for which the trial is testing a new drug. It also looks at both the absolute and the relative difference between the sort of desired demographics for a trial and the actual enrollment of subjects into that trial. It's also a tool that can be set up and used in real time by clinical operations, folks or CRO to monitor the screening and an enrollment rate for different subpopulations as a trial is progressing, so that there can be a shift in the activity level or pulling back on some sites that are already sort of reaching their goals, putting more resources into others. It's a tool that has a dashboard that lets you really sort of see the progress as it's being made.
Speaker 2:So we're getting good feedback from sponsors because it helps pull everything together. It gives them a sort of an epidemiologically based way of looking at their trial enrollment performance And, you know, and again, it is proving helpful in terms of, you know, adapting the approach in real time to ensure that a more representative population ends up in that clinical trial. So you know again, it's an evidence based approach. That's what we like. It uses real data, hard data, and we think we need more of that sort of embedded in the overall approach taken to not only executing trials but also designing the protocols for the trials, Because we know that has a big impact ultimately on the study participation as well.
Speaker 1:So, marie, it sounds like it's going to happen, but it may take a while. inch by inch, step by step, the industry is getting closer and closer, perhaps, to reaching its inclusivity destination, but we have to strive to do better, to try new things, to listen more and invest in the right stuff. I hope this message gets shared with the right set of ears, and I'm counting on listeners to help make that happen. Thanks for being my guest today, marie, and doing your part by crunching the numbers.
Speaker 2:You're very welcome. We're very passionate about the importance of advancing in this area And again to your earlier point, not limiting it to race and ethnicity. There's more dimensions to look at as well, but overall this is a way forward to improving our healthcare system and bringing those benefits to the entirety of the population who benefit from medicines being tested in clinical trials. So we're in this for the long haul, for sure.
Speaker 1:It was so good to hear Marie again. Thank you, and, as always, a big thank you to everyone out there for listening in. If you're not subscribed to this podcast yet, please consider going to Apple Podcasts and doing so right now, so you don't miss your monthly dose of news and perspectives. You'll be hard pressed to find anywhere else, and if you're up for it, i'd be so very grateful if you'd leave a rating and review on Apple Podcasts too. One final note If you like today's conversation, it is only a glimpse of what you can expect from the presenters and panelists we have on tap for CHI Summit for Clinical Ops Executives Europe, aka Scope Europe. Please plan to join us October 17 and 18 in Barcelona, spain, and please be sure to use discount code SOT10 for a 10% discount off any current rate. For more information, visit scopesummiteuropecom. Bye for now.