The topic of improving diversity in clinical trials has been at the top of the agenda at most health conferences over the past few years.

This is something which has been heavily acknowledged by the industry, including the US Food and Drug Administration (FDA), which has recently spoken out a lot about the lack of diversity in US-based clinical trials.

On June 26, 2024, the FDA released guidance on recommended steps for sponsors and drug developers to take to improve diversity in clinical trials. The guidance applies to both drug and device trials.

Sponsors are asked to consider several factors including site locations and community-based care as a way to make it easier and more accessible to diverse populations to be more involved in research.

Esther Krofah, executive vice president for health at Californian-based think tank, the Milken Institute, told the Medical Device Network that after years of campaigning, it is good to see such cohesive and stringent guidance in this area.

Abigail Beaney: Explain what is contained in this guidance and what precautions sponsors need to take when they are setting up these Phase III and pivotal trials.

Esther Krofah: We at the Milken Institute have advocated not only for the creation of these diversity action plans but generally for the increase of diversity in clinical trials so it's great to see this long-awaited guidance. The expectation of the US population is that we are including clinically relevant individuals in the study of new products, new interventions and new devices. When I saw the guidance, I was really encouraged to see the thoughtfulness of the FDA both in the range of the requirements and the structure of the guidance which was rational and cohesive while it allows sponsors and industry to respond.

We recognise that clinical trials are complex, and there are many considerations along the way. From a community perspective, however, what we are all looking for is that the industry has a good understanding of the disease being investigated - the epidemiology and prevalence of the disease and enrolling the patients that are represented by that data. As sponsors are pursuing the post-market and real-world setting, it is vital that those kinds of individuals were included in earlier clinical studies.

AB: What do you believe to be the biggest barriers as to why historically sponsors haven't been getting more representative and diverse populations enrolled in trials and does this guidance really address those barriers?

EK: The Milken Institute released a report on this topic recently that shows we still have a challenge, one of those being distance. In trials, we still have largely academic-driven clinical trials which happen primarily in academic centres on the east and west coasts. Patients can live upwards of two hours from these clinical trial sites so that is a challenge that needs to be addressed. Another challenge is: do you have the right principal investigators? We need to train and educate the clinical research workforce in such a way that it reflects the populations that we are targeting and addressing. Individuals want to be asked by someone who looks like them, so we need to have coordinators who are in that community or community health workers or other navigators, particularly given the lack of trust. What I saw in this guidance was the FDA acknowledging that outreach needs to happen and that sponsors need to target different kinds of sites and settings. What is key for that is that sponsors look at sites with a deeper lens and not just work with those sites that they're accustomed to working with, who can enrol as quickly as possible, but they need to work with sites that are going to allow them to engage with the right patient population. Following this well-laid-out guidance, the question is going to be whether the sponsors are following this up and are building up the infrastructure to increase diversity. It’s also not just the responsibility of the sponsors, there's a lot of work that needs to happen at the ecosystem level to get community health centres built up and able to recruit these kinds of patients that we desperately need in our trials.

AB: How far have sponsors got to go for people to feel that they can trust these companies to be involved in a clinical trial?

EK: Think about the Tuskegee trial or Henrietta Lacks, the community lacks trust so it is going to be very difficult for some people to come around. The biggest problem however within the community is that we are never asked in the first place. It is not just that trust question, we need to take it and flip it on its head to say, we need to create opportunities and long-standing relationships with the community to build up that trust. It's really going to be about the sponsors partnering with community-based organisations. This is not about any individual company coming and trying to resolve trust with them, it is about the industry as a whole showing that it cares about this issue of diseases that are prevalent within these communities and showing how they are going to partner with community organisations that have been there to support these communities and will continue to be there.

That's what I'm seeing and that's the approach that sponsors are taking. We have a lot of great examples of how these partnership models have worked really well. A great one is called Beacon of Hope, which involves several sponsors and academic institutions that are pulling their dollars together to build infrastructure at the community level. This kind of programme shows that we are going in the right direction, we just need to keep moving that way and not go back to the days in which we hovered and kept sites and trials limited to provide efficient execution of what sponsors needed for submission.

AB: Do you think that sponsors will be happy to make these contingencies like increasing the number of sites to increase the diversity in clinical trials given the financial implications attached to these?

EK: Sponsors now recognise that they need to be part of the overall solution around the broader issues of health outcomes. The most recent report from the National Academies called 'Unequal Treatment' showed that we have made no significant improvement with health disparities in this country in 20 years. These cost the US hundreds of billions of dollars annually, so we need to have a solution that is about the ecosystem driving toward the same goal.

AB: In the guidance, the FDA is providing a waiver for certain situations, have you any concerns that it might be used as a ‘Get Out of Jail Free’ card?

EK: What I was encouraged about was that they said these waivers will be rare and issued on a case-by-case basis, only with scientific basis or operational bases. It has been made very clear from the outset that this is not just about coming forward to say it can’t be done because it’s too difficult or because it's expensive, but rather true scientific issues or questions. While I am cautious about that, I would not say I'm worried about it. We need to make sure the early examples of how the FDA grants those waivers are proper.

AB: How vital are clinical trials to improve health equality across the US?

EK: What we are seeing in the data for many disease conditions, chronic disease conditions, cardiovascular cancer, diabetes and more, is that health outcomes for these underserved populations can be two to three times worse in either morbidity or mortality. We are now seeing in pockets of the country where life expectancy is declining. This is happening in the very communities that are left out of clinical trials and clinical research. With current innovations, sometimes access to clinical trials is considered standard of care so we are in some ways denying standard of care, by not being thoughtful and including populations that have the most prevalence of disease. It's not just a moral obligation, it's a scientific obligation, and a care and outcomes obligation. We must fix this, even now in 2024 there are still trials in the US with 80% white Caucasian men – something has to change.