Practical Strategies to Foster Diversity in Cardiology Clinical Trials

Expert investigators are recommending steps that can remove barriers to participation in cardiovascular clinical trials, with the aim of producing research results that are truly representative.

Despite years of discussion and efforts by government regulators and funders to encourage diversity, “cardiovascular clinical trials continue to underrepresent children, older adults, females, and people from ethnic minority groups relative to population disease distribution,” the authors point out in their paper.

Senior author Harriette Van Spall, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), said the movement to increase inclusivity started with the awareness “that our clinical trials did not include those who bore the burden of disease.”

Admittedly, “clinical trials are hard work and recruitment is a challenge,” so it can be difficult for individual trialists to know how to start to enrich trial populations, Van Spall said.

This paper, she told TCTMD, emerged out of conversations that took place during the European Society of Cardiology’s Cardiovascular Round Table held last year in Vienna, Austria, addressing the future of clinical trials. The perspective that emerged from those discussions has now been published online in Nature Medicine, with first author Faiez Zannad, MD, PhD (Université de Lorraine and University Hospital of Nancy, France).

We need to go beyond internal validity and think about external validity and research equity—these are not mutually exclusive. Harriette Van Spall

Celina Yong, MD (Stanford University School of Medicine, CA), commenting for TCTMD, agreed that the scope of the problem—and its many facets—have made it hard to bring about change. “Honestly, it's just so much work to make it actually happen” in the face of limited resources and logistical challenges, she explained.

This document, she said, is helpful in that it “comprehensively lays out what needs to change across the entire spectrum of clinical trial management: from engaging with social media to using [artificial intelligence] and digital tools to changing our inclusion/exclusion criteria, screening broadly, making trial protocols feasible, and even considering adaptive trial design.”

Usefully, the paper “integrates examples of real RCTs and how some of them did it right,” Yong added. “It gives us a real sense of how to translate these ideas into practice.”

She observed: “We’re consistently underenrolling important patient populations, and the message is that if we keep doing the exact same thing, relying on the same recruitment strategies and the same trial designs, we shouldn't expect a different outcome.”

Van Spall similarly pointed out that researchers put enormous effort into designing study questions and methods to be able to pinpoint the efficacy and safety of a drug or intervention.

“But we haven't considered enough the importance of creating evidence that is also broadly generalizable,” she noted, “and we need to include those aspects in our trial design: we need to go beyond internal validity and think about external validity and research equity—these are not mutually exclusive.”

By including participants from historically underrepresented groups, “we can generate estimates of efficacy and safety that apply to them, without relying on observational data to slowly accumulate in clinical settings,” said Van Spall. This may improve uptake of interventions, she suggested.

Yong agreed, adding that “as important as it is for trialists to think about these topics, it's equally important for the people on the receiving end—the clinicians—to recognize why we need data that applies to our patient populations.” As more inclusive trials are coming to fruition, the findings they produce sometimes are a departure from what came before, she noted. “When I'm sitting in front of my patient, it makes a difference if I'm informed by studies that actually represent them.”

Representative Trial Results

Van Spall described the paper as a road map for what should happen before, during, and after a trial to ensure the results are representative, including detailed advice on how not only individual trialists but also regulatory bodies, industry, medical societies and academic institutions, and journals can make an impact.

Specific sections are devoted to tips on:

• Recruitment (use of digital technologies, patient engagement, and site selection)
• Eligibility criteria (streamlined and justified)
• Informed consent processes (addressing literacy levels, language, and cultural barriers)
• Trial design (synthetic control groups, embedded trials, decentralized trials, and adaptive designs)

Inclusion must start at the top, Van Spall stressed, citing research that shows this can affect who ultimately takes part in research. “Some of the plan for diversifying our clinical trial enterprise should also include diversifying trial leadership and ensuring that we provide the opportunities and the resources for a broad range of people to lead trials. Diverse trial leadership is associated with diverse trial participants,” she said.

Moreover, change must also happen so that potential participants are willing to engage with trials, the authors say. “There is a need for education to improve population-based health and research readiness across all groups at the societal level, given the potential health benefits associated with trial participation. Measures to combat misinformation and ensure transparency in research and data collection are needed to foster trust in science.”

For example, thought should be given to how and where recruitment happens, “harnessing the potential of digital platforms, community settings, and clinical sites that serve diverse people,” Van Spall said. While eligibility criteria serve an important purpose, they can inadvertently exclude specific demographic groups, so must be justified.

If I'm sitting in front of a patient, I might have a different recommendation or think about a problem differently if I actually have data I can rely on. Celina Yong

Once enrollment begins, “how do we obtain consent in a way that meets ethical requirements, and is also adapted to the needs of patients and their culture? By culture, I don't mean just ethnicity: I also mean gender and family dynamics, as some like to include family members in the consent discussion,” Van Spall continued. “In addition, how do we apply strategies to burden patients less with research requirements, so that the person who provides care to young kids or a spouse can participate in a trial without feeling encroached upon, without having their familial responsibilities be at risk?”

After the trial, too, more work needs to be done, Van Spall suggested. “We also talk about: how do you disseminate information and mobilize knowledge in a way that could be transformative and help populations and individual patients be more research-ready for subsequent trials? Patients themselves, when meaningfully engaged as research partners, can help us mobilize this knowledge.”

Altogether, the amount of change needed is “a big undertaking,” she said, though hopefully this summary of what’s needed will be a start.

For Yong, an asset of this manuscript is that it covers all the stages of conducting trials, from very early to the very end. There’s no single area to focus that’s going to work in isolation,” she noted. “I think really we do need to be pushing on every single one of these factors.”