By Deborah Borfitz

December 17, 2024 | The U.S. Food and Drug Administration (FDA) expects sponsors of certain clinical studies to submit a Diversity Action Plan outlining enrollment goals, their rationale, and means of achieving those intentions, as the agency spells out in some detail in its much anticipated draft guidance issued in June. At the same time, pushback against diversity, equity, and inclusion (DEI) initiatives has been ramping up in industry hallways across the land to the point where merely uttering the term “DEI” can evoke sneers. 

It is a situation that is exhaustingly frustrating to people like industry veteran and medical affairs expert Marcus Dortch, PharmD, who has worked in various industry roles with clinical trial responsibilities. Political activists have turned a fundamental right to equitable healthcare into a divisive issue and it is “completely unfortunate.”  

Even without all the push-pull, it has been proven confoundingly challenging to increase the representation of diverse participants in clinical research, thereby ensuring the findings are applicable to the populations they’re intended to help, he says. And that is unlikely to change if companies don’t recognize the shortcomings of current approaches.  

The inconvenient truth is that the under-enrollment of marginalized groups is a multifaceted problem with no quick solutions, says Dortch. Too often, it is viewed as just another company initiative that can be tackled by a dedicated project management team with a task list and deadlines. 

From his perspective, needed change will only come from grassroots efforts where sponsors are putting their money where their mouth is. “We have to go out into the community and meet with not only our investigators but also our potential patients” and, like it or not, that takes resources and meaningful engagement with the community, he says.  

‘Competition for Attention’ 

So where, exactly, are DEI efforts going wrong? What exactly is DEI and who does it impact? Dortch believes one central issue is that all the attention being given to diversity has caused many groups to emerge who see themselves as marginalized. “Consequently, it seems to have become a competition to be noticed, quite frankly,” he said.     

For one trial in a disease state prevalent in African American men, diversity goals included their recruitment as well as that of transgender individuals born male but who identify as female—another key marginalized group for which research is desperately needed but is severely scant to date. In the end, “we cast a large net, and I feel that neither population got the focused attention that was warranted.” 

Attempts to mesh efforts across the two groups presented challenges, he explains. There were references to “intersectionality,” based on the idea that people have multiple identities, such as African American men who are also in a sexual gender minority (SGM). 

The problem then became how to focus on SGM individuals who are white, or non-SGM African American men who may be homophobic. “Would you speak to a group of people in a non-native language or dialect that is foreign to them, yet expect them to comprehend? This is all to say that an individualized approach may be needed for each affected population group,” says Dortch. “Identify your target, put forth the right resources to address that specific target, and don’t assume that things are mutually inclusive,” he advises. 

No ‘Magic Wand’

Mistrust can also be a major pain point when it comes to recruiting individuals of African American descent, says Dortch, referencing a discussion with one principal investigator (PI) in Birmingham, Alabama, working with younger-aged patients unfamiliar with the infamous Tuskegee experiment. “For whatever reason—only part of it having to do with the pandemic—there was just a mistrust toward healthcare in general that proved to be a hindrance to their practice and, specifically, outreach to minority populations.” 

Geography plays a key role, he adds. “I think one of the things we miss [on the sponsor side] is that we are putting a lot of pressure on sites to go out and target those [minority] populations, and majority populations as well.” Since sites “treat patients as one,” the onus is on companies to work with the right sites in the right geographies to properly diversify trials. 

In geographies like Birmingham that have a huge minority population, would-be participants are “just walking through the door,” notes Dortch. It was the reason the PIs here had success in recruiting them—not because they waved some “magical wand” to bring them in. “They were trusted providers within the community, so patients came to them organically.” 

Dortch says if he could wave a magic wand, he would begin by building alliances with disease-focused patient advocacy groups and community organizations. One big mistake he believes many sponsors are making is that they go cold into the community to recruit patients with whom they have no prior relationship.  

Instead, he would suggest that they build those alliances beforehand to educate and raise clinical trial awareness among people who, while perhaps at risk, are still healthy. “If they do become sick or come down with lung cancer or multiple myeloma, they’ll already know where to look for help... [and] where to send their afflicted loved ones or friends that they’re caring for,” he says. 

With no genuine rapport with the community on the front end, the unsurprising question on people’s mind is why the sudden appearance, he adds. In the absence of relationship and information, the suspicion of some will be that they’ll be treated like guinea pigs or lab rats. 

Taking Chances 

One problem impacting DEI efforts is that companies tend to go to the experienced, trusted sites first because they want to get contracts signed and studies set up as quickly as possible, Dortch says. They understandably wish to lower the risk of potential errors or missteps that might prompt an FDA audit. 

But resources need to be devoted to the training and mentoring of PIs of minority descent, as sponsors are doing in collaboration with National Medical Fellowships, to equip the research-naïve PIs best positioned to enhance trial diversity since they can double as a proxy to the community, says Dortch. Bloomberg Philanthropies also recently announced its support of future healthcare providers from diverse backgrounds to foster a new generation of PIs who will reflect that diversity in clinical trials, he points out. Companies should bear in mind that “a lot of patients from minority communities have better outcomes when they receive care from an individual from their same ethnic or racial group and there is data to prove that.”  

Dortch says his passion for research was ignited in 1998 when he completed an elective course on clinical trial design at the University of Tennessee Health Science College of Pharmacy. But as a young clinical pharmacist, he was getting nowhere on his own trying to make the pivot to industry—until one pharmaceutical company “took a chance” on him.  

Because the company “decided to take me under their wing, train me, nurture me... [and] put me on their speaker's bureau and advisory boards, to this day I feel some sort of allegiance to this company,” says Dortch. Sponsors should do likewise with research-naïve PIs from minority backgrounds, thereby building alliances with these individuals so that they become investigators able to recruit the minority patients needed in clinical trials. 

Technology Barriers 

A variety of technological solutions have emerged that are intended in part to reduce the barriers to clinical trial participation and reach underserved populations. To some degree, they succeed in doing this, says Dortch, citing J&J’s Research Includes Me educational website as well as tools such as electronic informed consent and patient-reported outcomes (ePRO). 

But technology can also be a hindrance when trying to meet ambitious diversity goals, particularly among people in rural communities, he says. In one recent study requiring participants to wear devices and make ePRO entries, for example, a lot of participants “weren’t comfortable using the devices and had a lot of technical issues with logging in and resetting passwords and not having reliable internet service.” 

It is important to remember that many people don’t have much experience using the kinds of technologies being deployed, or even have the desire to use them, Dorth points out. “We need to take that into consideration as we develop these technologies and... make sure the patient voice—including individuals from rural communities and from minority populations, and individuals who may have a lower education level—is part of the design of these products.” 

Technology vendors should be motivated to more broadly beta test their products, given the diversity mandate study sponsors are now under, he says. Sponsors will be directing their business to the players that can accommodate those needs.  

In the meantime, protocols might be designed such that they allow caregivers to help study participants with documenting information in an ePRO solution and utilize paper-based diaries as a backup, Dortch suggests. Sponsors also might want to think about providing support, either locally and in person or via a 24-hour tech helpline. From the perspective of rural populations traveling 60 to 90 minutes to a study site, telephonic assistance may be the only practical option.  

Machine Learning Models

There are at least two roles for machine learning when it comes to improving clinical trial diversity, says Dortch. Algorithms can be used to predict which sites and locations are more likely to add the targeted populations and to identify patients for prescreening from a merging of datasets, including electronic health records (EHRs), census data, disease prevalence data, social determinants of health data, and claims data.  

One challenge here is that machine learning algorithms can have biases, he adds. But that could be overcome by assessing the accuracy of their predictions and tweaking models as needed. “We have to allow them to do what they can [and] update them on the next run.” 

Some of the potentially useful data sources constitute proprietary information because the companies developing these resources understandably don’t want to just hand them over to their competitors, says Dortch. Fortunately, the more readily available data sources are themselves quite good—and, beyond identifying sites, might shed light on how successful patients will be throughout the study. 

Similarly, the reasons certain sites have a high screen failure rate might be predicted with machine learning algorithms. To that end, he says, “we need to document those reasons and put them back into the model to enhance its accuracy” in identifying the variables that matter, including protocol issues.   

Several private patient matching companies now exist that are applying machine learning to EHR data to highlight patients for prescreening, says Dortch. Depending on the disease state, “the time crunch can pose a challenge,” which might be remedied by putting devices in the hands of providers at the bedside entering the study criteria to make the match. 

Getting those who meet the prescreening criteria to then go carry out the screening remains problematic, he adds. “There are a couple of companies out there doing it with various successes... but the turnover of [prescreened] patients actually getting enrolled in a trial is fairly low.” His hope is that tweaking the models using smartphone apps or other EHR popups will help identify patients a lot sooner.  

‘Sky’s the Limit’

Pharmacists, being the “most community-connected provider,” have an important role to play here, says Dortch. Historically, independently owned pharmacies were visible “pillars of their community” and pharmacists behind the counter could be approached by simply showing up at the store, no appointment necessary. 

Pharmacy technicians, meanwhile, have been given more authority to carry out certain functions in the pharmacy setting, he continues. This leaves pharmacists with more patient-facing time, for example, to assist clinical trial participants using a required ePRO device to document those outcomes. Study participants might also use the Wi-Fi connection at their local pharmacy if connectivity is a problem at home. 

“Pharmacists are uniquely positioned to assist with clinical trials but they’ve just yet to be [so utilized],” says Dortch. Part of the problem is that many of the mom-and-pop pharmacy shops were bought out by the big chains that are now shutting down vast numbers of these locations. Both Walgreens and CVS recently announced plans to close many of their stores around the country due to low performance. 

Dortch is optimistic that more independent pharmacies will reopen, which is exactly what a friend of his did in Murfreesboro, Tennessee. Reeves-Sain Drug Store was bought out by Fred’s, which in 2019 filed for bankruptcy. That left a gap in the community that so bothered its founders that they reestablished the practice last year. The fact that it is again an independent pharmacy means “the sky’s the limit in terms of what it could potentially do from a clinical trial standpoint, or any pharmacy service standpoint.”  

When it comes to health disparities, whatever tactical approach is ultimately taken must be preceded by an acknowledgement that inequities exist—across racial, ethnic and sexual gender minority lines—and “it causes detriment but is completely fixable if we just put our heads together and give it the attention that it needs,” says Dortch.