Plotting the way forward on clinical trial diversity

As the old adage goes, the first step towards solving a problem is admitting you have one. For pharma’s clinical trial diversity problem, that first step was a monumental undertaking, but in the last few years, it’s one that seems to have been cleared. The next steps won’t be easy either. Making clinical trial diversity the status quo will require flexibility, accountability, collaboration, and an openness to new ways of thinking about trials. To find out more, we spoke with experts from across the industry who are doing the work to learn what it’s going to take to make real progress.

Clinical trial diversity has been gaining currency, at least as a talking point, for the last several years. And, most would agree, it’s about time.

“We’ve been doing trials the same way for five decades,” Christopher Boone, AbbVie’s vice president and global head of health economics and outcomes research, told pharmaphorum in an interview last year. “Truly, the exact same way. So, if there’s any area that’s ripe for disruption, I would say clinical trials are it.”

Like so many other industry disruptions, the recent prominence of clinical trial diversity work seems to have been pushed along by COVID-19, which disproportionately affected racial minority communities, as well as nationwide protests in the United States after the killing of George Floyd by police in Minneapolis in 2020.

“When the George Floyd murder happened, and the civil unrest in America happened, right around when we were in the throes of lockdown, it forced, not just Moderna, but the industry and the world overall to pause and take a look at what those racial inequities were and how we as an organisation and organisations across the globe needed to address them,” said Jameka Hill, senior director of clinical trial health equity at Moderna.

That reckoning gave way to pledges and reports and eventually an FDA guidance later that year. This has been followed by further guidance and even legislation: a 2022 omnibus funding bill signed into law late last year by US President Joe Biden included provisions requiring companies to submit diversity action plans for phase 3 drug studies and device studies.

“I think that with the omnibus that came out through the legislature at the end of 2022, it’s really applying more pressure to pharma to say, like, this is not only an ethical responsibility of yours, it’s a scientific and a medical responsibility,” Medable CEO Michelle Longmire told pharmaphorum. “We need to have more diversity in the clinical trials.”

Non-representative trials that don’t match the populations that interventions will be used in are a scientific concern, as well as an ethical one, as Longmire points out, because they affect the validity of the research, particularly when it comes to how treatments work in the excluded groups. But clinical trial diversity is also an equity issue, because, increasingly, clinical trials of new therapies are the best option available for treatment. And if that option isn’t available to a certain subgroup of the population, then their outcomes will suffer.

Ricki Fairley, founder and CEO of TOUCH Black Breast Cancer Alliance, shared her own experience – in which she survived triple negative breast cancer with a two-year prognosis because of experimental drugs – in a recent DiMe webinar.

“As I started my advocacy, I looked back at the history of the drugs that were standard of care [for triple negative breast cancer] and there were no black women in those trials,” she said. “Black women under 35 get breast cancer at twice the rate and die at three times the rate of white women, well before they would have that first mammogram at 40. We don’t have the drugs that would work most effectively because they were never tested on black bodies.”

So, what is being done so far to increase trial diversity, and what still needs to be done?

Getting away from the same old sites

Research sponsors never set out to run 80% white trials. The lack of diversity in clinical trials has arisen from systemic factors. For instance, pharma companies have historically liked to work with the same large, academic medical centres when it comes to trial sites – centres that have well-honed operational procedures, comfortably large patient bases, and an existing, low-risk relationship with sponsors.

Liz Beatty is chief strategy officer at Inato, a tech company that has developed a marketplace model to help connect smaller community sites to large sponsors. But the early days of that project were eye-opening, she says.

“What we realised rapidly was that no matter how much data we put in front of sponsors, around a wide range of research centres, they still pick the same sites they’ve always worked with before,” she said. “You already know how to contract with them. You already know something about their budget. Even operationally, there’s less risk because you’ve worked with them before.”

Many interventions have focused on de-risking and cost-consciously scaling the prospect of working with smaller sites that are more tied to the local community. Inato’s model is predicated on creating a two-way marketplace where community sites can actively woo sponsors, as well as being vetted to some extent by the platform.

Some pharma companies have simply taken the plunge to identify and work with these community centres themselves.

“At Moderna, when we are designing our clinical trials, we do so with inclusion in mind,” Hill said. “We select sites with the representation of the community in which we’re looking to serve and where the intended audience is in mind – as opposed to traditionally what’s happened is it’s kind of first come, first serve basis, right? You bring on the sites and the research facilities that, you know, historically have done a good job and they then bring in the participants from whatever background as quickly as possible.”

And this desire for diverse sites has brought whole new players into the market – players like CVS, Walgreens, and Walmart, which have all launched clinical trial groups in the last three years.

“Combating, working towards, and frankly, doing away with this notion of lack of diversity in clinical trials, it’s been a core part of the mission here and integrated into pretty much everything that we do,” Dr Owen Garrick, chief medical officer of clinical trial services at CVS Health, told pharmaphorum. “So, we got involved as a company with recruiting, identifying subjects for the COVID vaccine studies, and in those situations, we were extremely successful in helping the sponsors at that time increase the diversity of the participants. And that really prompted the enterprise to think about expanding more broadly and more thoroughly into clinical trials.”

Awareness and trust

Community sites are important not just because of demography but also because of the human challenges of clinical trial recruitment – which is to say, to get people into a clinical trial, they need to be aware of clinical trials, and they need to trust in the institutions carrying them out. This can be a tall order for communities that have been historically mistreated in the name of clinical research.

Awareness, at least, has increased in the wake of COVID-19.

“More people are aware of clinical trials for no other reason than what they saw and experienced during the pandemic and getting vaccines,” Abbvie’s Boone said. “So, layman’s understanding of clinical trials, I would say, is at an all-time high. And that sort of nets out a greater interest, curiosity, and hopefully participation in clinical trials.”

Trust is a harder nut to crack than awareness. One surefire way to garner trust, however, is to let people hear about clinical research from people who look like them.

“Who an individual receives their information from matters, especially in minority communities— it’s about trust and who’s going to keep me safe,” Hill said. “And we have found, and the data has proven that … especially in minority communities, if that individual is a person of colour, the trust increases, which also means likely that the retention increases, and our attrition rate decreases.”

Inato’s Beatty adds that these community sites are just better equipped, often, to have the kind of deep conversations that engender trust.

“Some of our sites in our research centres in the community actually have very deep ties to certain subpopulations, and they know that community very well. In and out. Those are the people they serve every day,” she said. “So, they know how to approach the conversation. They know how to involve their families. They know that sometimes you have to sit down, serve coffee or tea, and have a longer conversation, because those are the types of relationships that matter long-term in a very important healthcare decision.”

The importance of flexibility

COVID-19 spurred a rise in decentralised trials, utilising telemedicine and sensors, as well as home visits. And while it’s a separate trend from the push for diversity, there’s no doubt that they’re related.

Essentially, decentralised trials increase access and make participation easier for people who might be hampered by socio-economic factors that are often correlated with membership in a minority population— not having reliable transportation, not being able to take time off work to come into a clinical site, or not having access to childcare, to name a few.

“We want to try and look at ways that we can decrease that burden,” Hill said. “Can you go to your local pharmacy in order to have some of your follow-up visits as opposed to having to travel for two hours? Can we leverage telehealth? Can we even cut down on the overall number of visits? I mean, I think, as researchers, we’re always trying to gather more and more and more information, but we have to temper that with, well, what’s actually necessary that doesn’t increase the burden to those participants.”

Just being in those community sites goes a long way toward improving that access, as Beatty and Garrick pointed out, and technology can go even further. All of this is important because retention is just as important as recruitment for truly diverse treatments.

“You don’t want patients of any kind dropping off, but you want to make sure that a lot of the work that you spend in terms diversifying those that are recruited doesn’t go to waste, and they are part of the data set that is available at the end of the trial,” Garrick said.

Ultimately, every patient and every patient experience is different, so if you want to retain patients, you have to give them flexibility and optionality.

Curebase’s vice president of clinical trial innovation, Jane Myles, paraphrased Acclinate CEO Del Smith, who gives a good illustration.

“His example is, and he tells his story better than me, lots of people who are underrepresented in trials think of their home as a sacred space. All the things out in the world are hard, I have to overcome things out there, and when I go home, it’s my place. And so, his point is, not everybody wants to invite people in from the outside world to their place. You can’t assume that by adding mobile nursing visits, you’re going to meet the needs of those underrepresented people,” she said. “What you want to do, and what’s hard right now for trial teams, is build parallel workflows. Like, okay, if you want to go to the site, you can do that. You want to do this at home, you can do that.”

The way forward: Measurement and collaboration

Inato works with a variety of different pharma companies. Beatty said that there’s a range when it comes to dedication to the work.

“We see a wide variety of engagement and strategic focus on this topic. Some are really trying to be forward-thinking. It’s a problem they want to be a part of solving and a really critical part of their clinical trial strategy. Others are trying to figure out how we will do it,” she said.

Patient choice, trust, access, and shifting the locus of trials to community sites are all promising paths forward for clinical trials. But how can the industry writ large codify these best practices and make sure they become standard across the board?

Just before this story went to press, the Digital Medicine Society (DiMe) launched a DEI toolkit for digitised clinical trials, working with a number of industry stakeholders including several pharma companies to create the resource – and example of the kind of collaboration that will be needed going forward.

One aspect where industry collaboration will be key will be in standardising benchmarks and measurements, so everyone can get on the same page about what’s working and how much progress is being made.

“We have really shifted the paradigm of how we conduct our trials so that now every program we run has a rigorous kind of checkpoint of, okay, are the sites selected with inclusion in mind? What are the demographics that we’re leaning into?” Hill said. “Because, like with anything, if you don’t know where you’re headed and you’re not measuring it, you never know if you’re succeeding.”

Internal measurement – which is to some degree now being mandated by the FDA guidance – is a first step, but cross-industry conversations will be essential.

“We realise that even if we solve this with all of CVS’s patients, we touch a third of the population,” Garrick said. “There are still another two-thirds of the population that we don’t currently serve on a regular basis. So, we will, one, share the roadmap, frankly, because we think it serves US public health. Secondly, we’ll also engage with regulators at FDA and other places as FDA begins to implement some of the policy from recent legislation around, say, having a diversity plan as part of your research, what that could or should look like, and we can give some examples of what has worked well and what hasn’t worked well.”

Ultimately, it will take collaboration between pharma sponsors, research sites large and small, tech solutions, and, of course, patients to reach the goal of diverse, representative trials.

“I think this is a really complex problem,” Beatty said. “It’s not going to be an easy solution that gets there.”

Jonah Comstock is a veteran health tech and digital health reporter. In addition to covering the industry for nearly a decade through articles and podcasts, he is also an oft-seen face at digital health events and on digital health Twitter.

Don’t miss your complimentary subscription to Deep Dive and our newsletter

Plotting the way forward on clinical trial diversity

Getting away from the same old sites

Awareness and trust

The importance of flexibility

The way forward: Measurement and collaboration

About the author