This is the first of two parts on the developing participant diversity movement. In this part, WCG subject matter experts discuss the significance of the recent FDA guidance on trial diversity planning and how sponsors and sites should work together to position their trials and medical products for agency approval. Next week, part two will look at inclusion strategies sponsors and sites already are using.

The FDA’s recently issued guidance on diversity planning is more than the usual agency advice, experts say. By strongly encouraging sponsors to develop in-depth strategies for broadening participation of minority populations in their trials, the guidance is a signal to sponsors and sites that they need to get serious about inclusivity if they want to win FDA approval.

And with FDA Commissioner Robert Califf announcing loud and clear that “achieving greater diversity will be a key focus” across the agency, some industry-watchers speculate that trials with participant populations that aren’t fully representative of the general population will be viewed by the agency as inferior in quality.

The guidance, issued in April, outlines the key components of a diversity plan, which begins with an overview of pathophysiology data in underrepresented racial and ethnic populations. Different applications or uses of currently available prevention, screening or diagnostic strategies and treatments should be described and known similarities or differences in disease/condition among the underrepresented population should be discussed, it says (CenterWatch Weekly, April 18).

Trial diversity is also being pushed for on Capitol Hill, with one notable bill being the DEPICT Act, which would actually mandate diversity strategies and enrollment target reporting (CenterWatch Weekly, Feb. 7).

Lori Abrams, WCG’s executive director of patient advocacy and diversity, tells CenterWatch Weekly that despite the guidance’s draft status, the FDA is already asking some companies to submit diversity plans in their drug and device applications. The incentive for developing strong strategies, Abrams feels, is avoiding an FDA call for a postapproval trial if the agency questions a trial’s diversity.

And the consequences can be worse, according to WCG Vice President of Client Delivery Cristin MacDonald, who notes that she has seen an increasing number of trials sent back to the drawing board or completely rejected by the FDA for failing to meet the agency’s diversity expectations.

“The burning platform really hits the explosion scale when the regulatory agencies start holding organizations accountable in ways like study rejections, 483s, etc.,” MacDonald said. “We can talk about many things — quality by design, innovation adoption — but the moment that the FDA starts pushing back in these ways that have real implications for pharma organizations, the quality teams will take note and begin implementing more proactive approaches with their organizations.”

There’s a strong link between diversity and trial quality, says Emily Ricketts, WCG’s vice president of operational strategy and planning, and nondiverse trials could ultimately translate to hazards for patients.

“One of the dimensions of quality is patient safety and efficacy, and certainly if you’re not testing the drug in all segments of the population that has that condition, you’re taking a quality risk,” Ricketts said. “You want to have some way to say, ‘we know the risk is there, we want to mitigate it, we’re building it into our plans.’”

Ricketts says WCG has been getting daily calls from sponsors asking for help crafting their plans. Not all sponsors have been considering how to increase diversity in their trials over the past few years, she says, and while some already have diversity strategies and initiatives in place, others, such as newer biotech companies, may not yet have resources dedicated solely or extensively to diversity efforts. The same can be said for sites.

While a plan should begin at the sponsor level (with the sponsor determining what’s needed to support it, the financial costs, the process changes/strategic decisions required and the epidemiology of the disease/condition), it’s absolutely essential that sites are part of the conversation, Ricketts said. Although there are sites that are already well-versed in reaching out to and connecting with underrepresented groups, some may need extra support from sponsors. Conversely, sites shouldn’t be afraid to communicate with sponsors when they need a helping hand.

“You cannot have a sponsor-level diversity plan without including the sites in your plan,” Ricketts said. Sponsors may have some sites that are diversity leaders that don’t really need help, but other sites do. “It’s not that sites don’t know how to do it,” she added. “But they need support because they don’t always know where the patients are outside of their own systems or how to reach out to those patients.”

One solution is using large datasets that show sites where physicians are located in a particular geographic area. These data are highly valuable, Ricketts said, but they’re also expensive, and sites aren’t likely to have access to such information, nor should they be expected to know on their own where physicians are located. Because these datasets can be used to locate and connect with more diverse groups of patients, it would be wise for sponsors to share them with sites in an effort to help them forge referral pathways.

Sponsors could also consider bringing sites into their organizational, national-level relationships. These connections could then be tapped into at a regional and local level to introduce sites and connect them with patients and physicians in the surrounding community — for example, a sponsor could pay for site staff to attend events put on by one of its community partners and pass out flyers for trials as part of a diversity plan, she said.

“The guidance is forcing sponsors to sit down and think of a viable plan, looking at various aspects that they may not have looked at before,” Abrams said. “In the past, they looked at the sites they use over and over and said, ‘how can we help them add more diversity to patient populations?’” But now they need to consider multiple approaches to their diversity plans that they may not have considered previously, including bringing in new and more diverse investigators, building new sites in underserved areas, teaching sites with access to diverse patient pools how to tap into them, and others.