Clinical trial diversity

The FDA has taken another tangible step toward boosting diversity in clinical trials. The agency recently released a long-awaited draft guidance revealing more details about how sponsors can create Diversity Action Plans to enroll trial participants who more fully represent the people using products once they hit the market.

The guidance, which applies to some phase 3 trials, replaces an earlier, less detailed guidance document issued in April 2022. 

“Congress sought to fix the underrepresentation of minority patient populations in clinical research by requiring companies to submit their plans for enrolling trial participants that truly represent the patient populations for the products tested in the trial, otherwise known as diversity action plans,” said Rohit Nambisan, CEO and cofounder of Lokavant, a clinical trial intelligence platform. “The recent FDA’s draft guidance is the first step in carrying out the new law.”

Testing drugs in a diverse population helps ensure they work safely in a variety of patients. Older adults, for example, may take longer to metabolize certain medications, increasing the risk of toxic reactions at standard dosages. Of course, genetics can also play a role.

The FDA’s Diversity Action Plans call on sponsors to identify the ideal patient mix for a trial and outline a detailed recruitment plan.

The new guidance also spells out which trials need diversity plans, the nuts and bolts of plan formatting, timing and submission, and the waiver process.

“The guidance also urges sponsors and investigators to consider the many dimensions of clinical trial diversity, even those that extend beyond age, ethnicity, sex and race to enroll populations that represent the patients who will be treated if the product is approved,” according to a press release from the FDA. 

Challenges ahead

While pharma has generally been supportive of diversity initiatives, getting new faces into clinical research is not always easy and many trials are falling woefully short of diversity goals. 

Determining the right combination of participants may be challenging for some trials designs but straightforward for others, including common conditions where patient demographics are well understood, according to Dr. Pamela Tenaerts, chief science officer at Medable, a decentralized clinical trials software company. 

A recent Office of Inspector General report found that many NIH-funded trials weren’t attracting enough people from underrepresented groups. 

However, this new guidance may create another hurdle for sponsors to clear. 

“While the FDA’s requirement of diversity plans baked into protocol designs shall eventually yield many important benefits to clinical sciences, and humankind … [and] clinical trial sponsors are now saddled with even more complexity to manage, more data to absorb, and more risk,” Nambisan said.

Although the guidance isn’t final, organizations should prepare and note similar state laws cropping up across the country, said Julie Ozier, senior vice president of IRB review at Advarra. 

“For example, Washington State passed a Diversity in Clinical Trials Bill requiring investigators to collaborate with community-based organizations and use methods recognized by FDA to identify and recruit underrepresented populations,” she said.

The FDA’s 2022 draft guidance called on organizations to create Diversity Action Plans, and after later analyzing 91 oncology submissions, the agency found that 13% omitted required elements. Tenaerts recommends that drugmakers review these findings to help avoid common missteps.

While many companies already have their own diversity plans in place, changes to real-world outcomes will likely be incremental.

“Now that we have a draft guidance outlining the requirements for diversity action plans, we will see more organizations developing smarter plans,” Ozier said. “But I think it will take time to see meaningful results and improved representation in clinical trials.”

When it comes to fomenting distrust in medical advances among people of color, the infamous Tuskegee experiments still play a major, disquieting role. Residual effects of the study that left hundreds of Black men untreated for syphilis without consent in the 1930s — and subsequent confirmed suspicions of scientific misconduct — carried through to the ongoing fight against HIV and into the COVID-19 pandemic in which so many more lost their lives.

While that distrust is deserved, it makes it more difficult for public health professionals to close disparities faced by minority populations in the U.S., said Dr. Reed Tuckson, a physician and founder of the Black Coalition Against Covid. He has also served as the commissioner of public health for Washington, D.C., in the 1980s and a vice president at UnitedHealth Group.

“It is frustrating to me that we have done nothing in 40 years to take Tuskegee off the table — that the No. 1 thing I would have to fight with HIV was Tuskegee, and the first question I was asked in my first town hall on COVID was Tuskegee,” Tuckson said. “It is a terrible indictment of America’s healthcare delivery, its health policy and its health promotion and prevention industries.”

A momentary success

In a recent paper written with James Mansi, Moderna’s vice president of North American medical affairs, Tuckson and colleagues reported that “uptake of the 2023/2024 COVID-19 vaccine was far from optimal,” falling particularly hard among U.S. minority groups. The decline followed a period of success when vaccination rates among Black Americans were reported in January 2022 to have risen sharply due to a large mobilization effort, closing the gap for a short time between the “two Americas,” Tuckson said.

That initial turnaround was a surprise to Tuckson and comprised one of the major lessons he took from the pandemic: reaching a community with factual, easily understandable health information can be accomplished. Still, a lack of consistency in messaging and required funding lies at the heart of health disparities in the U.S., he said.

“Black communities and health organizations are underfunded and only episodically funded for the disease of the week, crisis to crisis,” Tuckson said. “We jump from ice floe to ice floe without any sustainable infrastructure — there’s no garden, no oasis, you just see individual plants poking their heads through cracks in the concrete despite the sporadic funding year after year.”

The relative success of Black communities to rally around COVID vaccinations and preventive care came despite many hurdles, he said. Clinical trials with underrepresented minority cohorts, limited supply causing inequity in vaccine distribution and miscommunication among health professionals to communities of color all created challenges that leaders had to face.

“Success is relative,” Tuckson said. “We’re proud of the things we’ve done, but there’s such a long way to go and every day that trust is being eroded in every way possible.”

Calling on trusted messengers

From failures in the healthcare delivery system to misinformation and disinformation still rampant today in prevention circles, “that work [to build trust] is still very hard,” Tuckson said.

One lesson ingrained during the pandemic is that trusted messengers are key, he said. From pastors and ministers to fraternal organizations, as well as nurses, physicians and other health professionals of color, factual information from people in the community is crucial to sending the right message.

Dr. Kizzmekia Corbett, an immunologist who helped bring about COVID-19 vaccines through the NIH’s Vaccine Research Center, was an important role model and symbol for overcoming distrust, Tuckson said.

That’s where pharma can play a part, as well, he said.

“I would urge the pharma community to continue not only its hiring of the best scientists but to make sure they’re hiring excellent clinicians and scientists of color in responsible positions,” Tuckson said. “It’s important for the nation to know that we are in the room, not like the Tuskegee experience, but in decision-making power.”

Proactive, coordinated effort

The pharma industry has a notorious reputation problem, and not just among people of color. But rather than try to step back and let that reputation fall into the shadows, pharma companies — and other sectors in healthcare — need to step up and engender trust proactively, Tuckson said.

“Every single component of the health and medical care and policy system has its own challenges, and we cannot afford to have any sector decide to walk away or to be driven from the conversation,” Tuckson said. “Lord knows the history of misbehavior on the part of physicians, pharma, health insurance, you name it — every sector therefore has to be in the game and has to accept responsibility.”

The COVID pandemic illustrated that the disparate parts of the healthcare system can work together to handle a worldwide crisis, Tuckson said. Even with the missteps along the way, the cohesive effort has built momentum for the next health scares down the road.

“We’re in a better position because the resources at the community and national level are now more aware of one another, more coordinated,” Tuckson said. “The real issue now is to build on everything we’ve learned with the funding necessary for a sustainable infrastructure not only for the next pandemic, but for the high-priority epidemiological challenges that have always inflicted and plagued the Black community.”

Tuckson praised efforts undertaken by pharma companies to support higher vaccination rates among people of color, build trust through key messengers and make vaccines easier to find. Moderna and others, for example, have pushed for approval of a combination flu and COVID shot to improve vaccination rates. 

While the staggering loss of life in times of health crisis has shown the shortcomings of a health system not built with everyone in mind, Tuckson said, the efforts underway to close the gap make him optimistic.

“What is common to both COVID and HIV is the sub-optimal availability of an organized, engaged community infrastructure that has the strength and resources to fully exercise its capacity,” Tuckson said. “What is also common to both [HIV and COVID] is the extraordinary resolve and energy and determination by community and faith-based organizations in the minority community to fight for their own lives, and that was dramatically demonstrated in the COVID pandemic.”

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Oncology clinical trials are different. They have complex trial designs and with advanced treatments only getting more precise, the complexity will continue to increase. Oncology trials demand thorough attention to detail and a streamlined process to ensure that promising therapies reach patients swiftly and safely.

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Navigating the Phases and Challenges of Oncology Clinical Trials

Oncology trials are designed to evaluate the safety, efficacy and optimal usage of novel therapies for specific indications, offering hope to the millions of people affected by cancer. These trials are broken up into four phases:

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The path to developing effective oncology treatments has its own unique challenges. Patient recruitment is often a significant hurdle, as finding suitable candidates who meet the specific criteria for each trial can be difficult and may require broad reach across multiple geographies. Additionally, the diversity of cancer types and variations in patient responses add layers of complexity to these trials. Precise data collection is extremely important when it comes to ensuring accuracy and reliability. Overcoming these challenges necessitates a combination of experience and scientific expertise, enabling researchers to design robust trials and interpret complex data.

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Stay connected with insights from our experts. Follow LabConnect on LinkedIn for the latest, including excerpts from our blog, project examples and case studies and current job opportunities with our world-class team.

Among the strategies Big Pharma is employing to achieve more equitable health outcomes, AI is now playing a larger role. For AstraZeneca, a series of AI-based partnerships and screening initiatives is setting the stage to gather and use data for cancer patients in neglected ZIP codes.

As it stands, innovation is outpacing health equity, widening the gap in oncology between patients who have access to novel medicines and those who do not, said AstraZeneca’s senior vice president and head of U.S. oncology Mohit Manrao.

Black Americans have higher death rates than any other racial group for many cancer types, according to the NIH’s National Cancer Institute. Furthermore, people without access to healthcare are more likely to be diagnosed later in their disease trajectory, putting them at greater risk of death.

“Science is moving so fast, but the job isn’t done after that,” Manrao said. “The challenge we have at a local level is that disparities are increasing, and more and more people fall through the cracks. Everyone in the system has good intent, but it’s important that as an industry, we embrace opportunities and collaborate to solve for it.”

AI is one of the most promising opportunities for improved health equity, Manrao said. By teaming up with diagnostic makers and AI companies, AstraZeneca wants to use data to expose the disparities in care, and address screening and access issues that exacerbate them. Manrao said AstraZeneca’s mission goes beyond developing oncology meds like the blockbuster Enhertu, which was originally approved for breast cancer in 2019 and recently scored a new expanded indication, and AI can find patients who need it.

“There is no reason that a Black woman with breast cancer in New York should have different outcomes than a white woman living in California or Atlanta — the ZIP code lottery exists today,” Manrao said.

Here, Manrao discusses the effect data-driven AI can have on the understanding and mitigating disparities in cancer care, the partnerships AstraZeneca has sought to bring AI into the fold, and how the feedback loop will also help drive better R&D for more equitable outcomes down the road.

This interview has been edited for brevity and style.

PHARMAVOICE: How do you characterize the impact that AI can have on patients, particularly from a health equity standpoint?

MOHIT MANRAO: Availability of data has multiplied in a multitude of ways, both in terms of genomic data and multi-omics data at a patient level and a customer engagement level.  Similarly, science, technology and data are converging very quickly, and that helps us believe we can have an impact on patients at every level. From a health equity lens, beyond our bread and butter in biopharmaceutical innovation, we want to start looking at the entire patient pathway and ask new questions. Are patients getting screened? What are the risk factors? Are they going to screening centers? Are they followed up appropriately in the system at the right intervals to be detected early?

Because of the socio-economic determinants of health, we need to have individualized interventions to solve for specific barriers that get in the way of a specific patient.

Because AI is trained using past examples, bias often finds its way into algorithms. How do you advance AI so that it can actually introduce progress rather than remain with the status quo?

It’s a super important point. Being aware of bias that would get into a system and putting checks and balances around it can help us look at health equity. Across the pharmaceutical value chain, it starts with inclusive R&D. We have drugs that get developed based on biosamples, and we’re working on creating diverse biosamples that are representative of the populations we serve. Of course, we can’t do that alone. So working at a local grassroots and community level to bring those diverse biosamples into drug development helps ensure that patient recruitment meets those goals. 

For instance, at a clinical trial centered in a community in New Jersey that is 18% Black, we work with them to ensure that not only 18% is recruited from that community, but more so that we can help dig and gather data. And all this serves to help AI predict without bias.

Your AI strategy has been heavily partner-focused. How does a potential partner stand out within the AI boom?

When ChatGPT came out, it exploded into the world in a visible way, but we have been using AI in different parts of the value chain already. We have more than 700 data scientists who are AI experts working in different parts of our organization from early drug discovery to development to commercial organizations and operations. We’ve embedded them to think in terms of looking for partnerships — we can’t move forward alone. So looking at the right partners with the capabilities, values and vision in terms of transforming cancer care is very critical. For example, in early detection, there are a multitude of challenges. If we see that tissue-based screening is a challenge, we work with blood-based companies to look at how we can help improve their assay. That led us to work with Grail in that space. 

Companies like Qure.ai can use technology to find lung nodules on X-rays that a naked eye couldn’t see, and companies like Clinithink have natural language processing that can go into electronic medical records. These are all important steps.

At the same time, let’s take the example of lung cancer — screening has been approved in the U.S. since 2013 and even a decade later, the uptake is dismal at only 5% to 6%. Socio-economic determinants are a barrier to lung cancer screening, and we’ve worked with the Association of Cancer Care Centers to understand and work with local communities, and use that rich data to inform where the pockets are, such as a rural Appalachian screening program for lung cancer in Kentucky. 

Similarly, we just announced a partnership with the University of Maryland system across counties in the state to identify at-risk populations. These academic and community institutes play a big part in the data-gathering process.

As you collect data, how does that feed back into the drug discovery and development process?

It’s critical that we put patients at the heart of drug discovery and development. All this data, in many ways, unlocks opportunities to uncover true unmet needs for patients, and the bigger picture is we want to eliminate cancer as a cause of death. Understanding through these datasets why the disease is progressing and informing R&D by identifying patients earlier. The partnership with Grail, for instance, helps us not only identify patients but also to look at the data and [see] which patients within this group are high-risk and the kinds of interventions they need. So this is integrated across the internal value chain.

The secret sauce for us, and it’s not truly secret, is external collaboration. We don’t shy away from partnering with the right party. What stands out for us and for anybody who wants to move the needle for patients is that we can’t work in silos.

“Men with prostate cancer” is a common phrase in clinical trial protocols for prostate cancer treatments. But for pharma and biotech companies that want to move the needle on improving clinical trial diversity and including more LGBTQ+ people in their research, a problem has emerged with these phrases.

“There are lots … of individuals who have prostate cancer who don't use the pronouns he/him,” said Mark Wildgust, vice president of global medical affairs for J&J's oncology division and PharmaVoice 100 honoree. “There are lots of individuals who have prostates that are transgender women, nonbinary or intersex.”

That’s why J&J is actively working to de-gender its clinical trial protocols by replacing gendered words like “men” and “women” with neutral and inclusive words like “people” or “patients.”

“De-gendering a protocol means using inclusive language that removes this idea of gender,” Wildgust said.

Changing the phrase, “men with prostate cancer” to, “people with prostate cancer,” effectively kicks open the door to a clinical trial for people who would have otherwise felt excluded.

“We believe that we should understand how our medicines work in all people,” he said.

It’s part of a larger effort at J&J to improve clinical trial diversity.

“As a patient, you want to know that what you’re taking works for you,” Denise Bronner, director of diversity, equity and inclusion in clinical trials at Johnson & Johnson Innovative Medicine, told PharmaVoice last year. “And if someone like you was never included in the data, but this drug is approved, how would you take that? Would you even want to take that type of medication?”

Excluding transgender and nonbinary people from clinical research is an ongoing challenge for the industry. Although an estimated 1.6 million Americans identify as transgender or nonbinary, less than 1% of U.S. clinical trials include patients from these communities, according to a Parexel report.

Moreover, Wildgust said the pharma industry hasn’t historically done a good job including or engaging with the LGBTQ+ population in general. Some companies don’t even collect sexual orientation and gender identity (SOGI) data in their clinical trials.

“The first part is making sure our trials are inclusive. The second part is [doing] a better job of understanding if we are including those individuals,” Wildgust said. “To be counted, you need to count. Imagine if you had a demographics table in a study report and didn’t say if patients are African American or white or Asian.”

How J&J is making changes

At J&J, the shift started with LIBERTAS, a phase 3 clinical trial in prostate cancer that Wildgust said is J&J’s first de-gendered, transgender-inclusive research study in cancer. It’s actively enrolling now.

“When a lot of people think about prostate cancer, they think about men. But there are many individuals who have prostate cancer, who have prostates, who may not identify as a cisgender male,” Wildgust said. “By de-gendering or removing gender terms … or gender biases, you can show inclusivity to all individuals.”

The LIBERTAS trial involves J&J’s Erleada, which became the first approved drug for non-metastatic castration-resistant prostate cancer in 2018. Now a blockbuster med, J&J has continued developing Erleada, and launched a once-daily option for the drug last year. The LIBERTAS trial will test if the drug improves progression-free survival and other quality-of-life measures when used in combination with intermittent — versus continuous — androgen deprivation therapy.

The company is working to make these protocol changes in its other clinical programs.

“LIBERTAS was the first across our oncology organization,” Wildgust said. “We de-gendered … our master clinical trial protocol within our oncology division, which means that every study we write is inclusive. And it created an enabling environment for the sexual and gender minority community to participate in these trials.”

One strategy has been to de-gender informed consent to broaden the eligibility criteria.

“We don't recognize a cancer by sex. We recognize it by somebody who has a prostate,” he said. 

In addition to making changes around protocols and data collection, J&J provided culturally inclusive training for its internal teams that cover everything from understanding disparities to using the right gender-affirming words and terminology to build respect and trust with patients “so those individuals feel comfortable and safe participating in clinical trials,” Wildgust said.

To do this, they worked with an internal J&J employee resource group called Open&Out, as well as with Eli Green from the Trans Affirming Training & Consulting group to create internal education materials and build cultural competency. They’ve also built a scientific and patient advocacy steering committee “that reflects the diversity of who we wanted to include in our studies.” That guidance has helped create protocols, informed consent, recruitment materials and educational resources, Wildgust said.

“We’ve been thoughtful and very intentional looking at inclusive practices, and we've done that through strong internal and external partnerships that we’ve built,” Wildgust said.

Creating broader change

In addition to its internal work, J&J hopes to be a leader in gender inclusive clinical trials across pharma. For instance, it’s creating an educational toolkit for building welcoming and affirming LGBTQ+ clinical studies it will use internally and then offer to other companies for free later this year.

“We're in the process of building that material, and our plan is to give that toolkit away to anybody who would like to get access to it. On the pharma side sometimes things are competitive, [but] some things are non-competitive,” Wildgust said. “We believe this educational toolkit will be a very tangible way in which [pharma companies] can remove some of those barriers around data collection and have really good culturally responsive ways in which to engage these communities.”

The exclusion of women from clinical trials is rooted in historical tragedy. In the 1950s, when nearly 20,000 Americans took part in clinical trials for the drug thalidomide, including 600 pregnant women hoping to ease morning sickness, the study resulted in a massive wave of serious birth defects, including missing or deformed limbs.

The wide-scale shock helped prompt a 1977 FDA recommendation to exclude women of childbearing age from phase 1 and phase 2 trials, stalling a growing push at the time to bring more women into scientific research.

However, scientists found that excluding women from early-stage clinical trials came with its own set of consequences, including limiting the understanding of how women respond to various medications. So, in 1986 the NIH took the first in a series of steps to bring women back. 

Today, trial participation among women has increased, but they are often still underrepresented. 

A 2022 study found that women only made up, on average, 41% of more than a thousand reviewed trials — numbers that were often lower than the percentage of women affected by the diseases studied. In psychiatry, for example, women comprise 60% of patients but only 42% of trial participants. 

There is a renewed push to encourage more female participation and more studies geared toward women’s health. 

“Historically, conditions that primarily affect women have just not been researched at the same rate as indications that affect men,” said Cara Brant, CEO of Clinical Trial Media, a global recruitment and retention company. “And this is throughout the healthcare industry, both government and private.” 

But recently, progress is being made in research for diseases that primarily affect women, including breast cancer and endometriosis, Brant said. In March, President Joe Biden announced a new initiative to expand and improve women’s health research, which adds to ongoing efforts to diversify trial participation. 

“It's starting to feel like there's momentum around women's health research,” Brant said.

Encouraging participation

Enrolling women in clinical trials is crucial because women often react differently to drugs and have different presentations for many diseases, including cancer and cardiovascular diseases. 

“Our bodies are different. We process and metabolize medication differently,” Brant said. “Understanding that, I think, will help to improve drug effectiveness, safety and tolerability.” 

Women are also disproportionately affected by diseases such as Alzheimer’s disease and autoimmune disorders, and need better options for female-specific problems, such as menopause symptoms.

Women appear willing to sign up for trials. COVID helped raise awareness about the role and availability of clinical trials, Brant said. 

“It opened everybody's eyes to this industry that helps bring medications to market faster, and creates opportunities to see specialists and to get expert medical care in under-researched areas,” she said. “Interest is through the roof right now and I think women are just as interested as men, if not more.”

Although they may be eager to sign on, logistical barriers can block their path. Often they are the primary caregivers for children or aging parents in addition to work and may struggle to balance those responsibilities with that of a clinical trial commitment. 

“It’s almost impossible for moms to find time for themselves, much less the time that’s needed to participate in a clinical trial,” Brant said. “One thing that we hear consistently from women is that they have challenges with childcare and coming to appointments and just finding time for a scheduled visit.” 

Sites looking to increase women’s participation need to make changes to encourage participation, she said.

For one, they need to increase appointment flexibility, she said. Adjusting site hours to include later appointment times or weekend visits makes it easier for women to make the schedule work. 

“We have to look at how to be flexible and adapt to their lifestyle and their needs,” Brant said, pointing out that remote visit options offer another convenient option. “Maybe there's a telehealth visit or they can have their labs done [locally] as opposed to attending the site — it takes a lot of thoughtfulness and creativity, but I think that's what's needed at this moment.”

Trials should also make space for children, so women who can’t find childcare don’t have to cancel appointments or drop out. 

“I do think that when sites create a friendly environment for a woman who may have to attend an appointment with her child, it’s going to go a long way.” Brant said. This can be as simple as offering puzzles and games to keep children entertained in the waiting room. “Women love to know that their children are being thought of. That's a reflection on them and it makes them feel more relaxed, more comfortable. They don't have to feel on edge about bringing their child.”

Sites also need to open the lines of communication to get better results, Brant said.. 

“What we hear frequently from any participant is that for people [who] are new to clinical research there’s a lot of anxiety around what to expect: Where am I going? What happens at the study visit? How many visits are there? How long is it going to be?” Brant said. 

Providing guidance and information can ease uncertainty and make women more willing to participate. Asking participants for regular feedback to identify improvement targets can also help. For example, a survey might reveal that parking at the site is challenging, adding 20 to 30 minutes to the visit. 

“This person, who was showing up for a visit on time, is now going to be late to work,” she said. “That's a problem. It's such a small thing, but it's real.” 

Because trial participation can be taxing, sites should also let women know they appreciate the effort, acknowledging the sacrifice participants make. This might include a handwritten thank-you card or a small, inexpensive token of appreciation that shows you're thinking about them, Brant said. 

“I think women, like everybody, want to be heard, so give them an opportunity to have a voice and be included in the clinical trial process,” Brant said.

Improving clinical trial diversity remains an industry and regulatory linchpin in efforts to boost overall health equity — and by some accounts, progress has been frustratingly slow.

Recently, Congress thrust the issue to the forefront by mandating diversity in clinical trials within the 2022 omnibus spending bill. The FDA has since taken up the charge, publishing a draft guidance that would require industry sponsors to develop and submit a diversity plan, including enrollment goals for underrepresented racial and ethnic participants, before pivotal clinical trials for drugs. The law required the FDA to draft more guidance addressing how and when drugmakers must submit these plans by the end of 2023, but the agency hasn’t made it available yet, and some lawmakers are asking the FDA to produce it.

Meanwhile, major pharmas have devised their own strategies to tackle the issue. Japanese drugmaker Takeda Pharmaceuticals, for example, has set a lofty goal of achieving “unprecedented patient diversity” in phase 3 trials for a key psoriasis candidate, according to Karen Correa, vice president and head global clinical operations at Takeda. 

The company’s TAK-279 is enrolling participants in a phase 3 trial with the ultimate goal of participants matching real-world data and the overall patient population. Takeda reported positive results from its phase 2b studies last year for TAK-279, an investigational oral allosteric tyrosine kinase 2 (TYK2) inhibitor, for treating plaque psoriasis and psoriatic arthritis.

Takeda acquired TAK-279 last year from Nimbus Therapeutics in a deal worth $4 billion, with high expectations the drug candidate would bulk up Takeda’s immunology portfolio. The candidate has been plugged to rival Bristol Myers Squibb’s psoriasis drug Sotyktu, which reached $170 million in global sales in 2023, according to the company’s end-of-year earnings report. As part of the deal, Takeda will make two additional and separate $1 billion payments to Nimbus after sales from the TAK-279 program reach $4 billion and $5 billion. 

The phase 3 trial designs include a diversity action plan that Takeda based on the FDA’s initial guidance, according to Correa. In fact, the company has added diversity action plans to all new clinical trials since June 2022. 

“I don't feel [there’s] pressure [from the FDA],” Correa said. “I think if anything, it's more about holding us accountable to do the right thing.”

Slow burn to overtake industry standards

In psoriasis, a lack of trial diversity can lead to critical gaps for physicians’ understanding of the disease and the way it presents. For example, psoriasis, which can cause scaly patches, can appear differently across skin tones. 

“With patients of different color skin, you will see a difference in the disease,” Correa said. “For a lighter skinned patient, plaque psoriasis may present as red or pink; in a darker skinned person it may present as gray or violet; and in Hispanic patients it may appear as salmon colored or white-silver in appearance. If the research and prior studies are all white patients, and the data and the information and the imaging were all put in for white patients, imagine a physician or healthcare provider trying to diagnose a patient and leveraging the tools they have in front of them that might not represent the patients sitting in front of them.”

Beyond diagnosis, people of different races, ethnicities and sexes can also react differently to drugs and medical products, according to the FDA. But creating a trial that matches up to real-world patient populations requires an intentional approach, Correa said. Operational barriers and access to clinical trial sites can lead to underserved demographics and underrepresentation. 

Takeda’s diversity strategy includes its PAVE approach — partnering with community stakeholders; addressing operational barriers that impede patient access; verifying that diversity and inclusion goals represent real-world data; and enhancing the diversity of investigative sites. In particular, partnering with community stakeholders has been effective, according to Correa.

“We have a really big awareness campaign where we're making sure we're collaborating and coordinating with other organizations within plaque psoriasis, [such as] pharmacies and different types of organizations and campaigns that help ensure people understand what is going on in complex psoriasis, and then making sure they have awareness of our trial,” Correa said.

Within their diversity action plans, Takeda is aiming to be above the industry standard when it comes to enrollment. 

“We are tracking well above the industry benchmark, which is 25% or more of our clinical study sites are enrolling at least one patient from an underrepresented minority population,” Correa said.

However, the benchmark itself could be considered low. 

“It's definitely a place of improvement, which is why we have the requirements going forward,” Correa said. “We have to start somewhere. [If] more than 25% of sites have at least one patient of an underrepresented population, you're still moving in the right direction.”

With a more diverse patient population represented in clinical trials for psoriasis, Takeda is aiming to improve outcomes down the line. The implications are broader than the company’s own phase 3 studies.

“Maybe what we'll see is more patients will be diagnosed earlier … they will be treated sooner and their quality of health will be better,” Correa said. “And that's the really important part to impact health disparities.”

Among the many falsehoods surrounding diversity in clinical trials, the notion that people of color simply don’t want to be part of drug studies is one of the most harmful, said Quita Highsmith, Genentech’s vice president and chief diversity officer.

Following a global study the biotech giant conducted during the COVID-19 pandemic that enrolled a large majority of Black and Hispanic patients, Genentech’s latest shot across the bow for clinical diversity was a trial exclusively in patients with multiple sclerosis from those communities. Genentech sells the blockbuster MS drug Ocrevus.

Highsmith, a former PharmaVoice 100 honoree, said the trial achieved a breakthrough in proving that reaching diverse patients isn’t a detriment to the science. Black and Hispanic patients make up almost 20% of the MS population but clinical studies often fall way short of that representation, according to the company.

The problem, Highsmith said, has been that trials haven’t historically been designed to accommodate the needs of these communities. So when a trial like this one — called Chimes — meets people where they are and finds common ground with advocacy groups and clinical investigators, patients receive more equitable care.

At a time when political backlash has been rising against diversity initiatives at corporations, and in education and healthcare systems, Highsmith said it’s even more important to question the status quo.

Here, Highsmith discusses the myths surrounding a lack of diversity in clinical trials, how collaboration can benefit the biopharma industry in its efforts to change and how health equity rises above political posturing.

This interview has been edited for brevity and style.

PHARMAVOICE: What are the greatest challenges to diversity in clinical trials as you see it?

QUITA HIGHSMITH: There are a lot of myths. One is that patients of color don’t want to participate in clinical research. Myth No. 2 is that, if they participate, it’s going to slow down the research, and we’re not going to be able to get the products on the market. Myth No. 3 is that patients are not going to be compliant. And these myths have meant that they have been excluded and have lower participation rates. In our research, when people of color are asked to participate, they do so at the same rate as everyone else. They want to be part of the solution. When we select sites in areas with high unmet need and populations that are going to be representative of patients of color, we’ve found that these sites are enrolling Black and Hispanic patients two times faster than other sites with the same study. If you go where the patients are and ask them to participate, they will.

These myths sound like they come from a lot of false assumptions. Can you talk about how you get past these assumptions?

One of the things we did during the pandemic was a study called Empacta, looking at hospitalized patients with COVID, and 85% of study participants came from communities of color. And what we learned was that if you go to patients, they will participate. And if you partner with sites, even if they haven’t done clinical research with us before, they are willing to work with you to overcome barriers so that you have a real-world patient population versus a fairy tale population.

Then, when we took a look at the unmet need of multiple sclerosis, we had those learnings from COVID to do this study called Chimes. The scientific question we wanted to address was that many people believed that multiple sclerosis was a disease that impacted white women. And what we know is that the epidemiology shows that Black and Hispanic patients oftentimes are disproportionately living with MS, but they’re diagnosed later. So, working with the community and Dr. Mitzi Williams, a neurologist out of Atlanta who was the lead author of the study, we were able to enroll ahead of schedule and retain those patients. And we found that safety and efficacy was the exact same as the general population, which gives organizations comfort knowing that you can bring in real-world patients to a clinical study and get a similar outcome.

With these gaps in data, how can Genentech and others in the industry use technology to improve patient diversity?

Actually, one of the areas of concern I have is artificial intelligence. The reason for that is if we look at the genome-wide sequencing database, it’s not very diverse. There’s very little data out of Africa — less than 1%. And when we think about AI using algorithms to make treatment decisions, and that algorithm doesn’t have data from people of color, we have to be very mindful that we don’t continue with the issues of the past. We’re thinking very proactively about ensuring that we have representation in the datasets we’re using. One of the things I’m excited about is the FDA’s omnibus legislation that all phase 3 programs have a diversity action plan to be considered for approval. That kind of ripple effect from the agency is going to advance opportunities to ensure patients are actually in the clinical trials.

Do you feel that Genentech’s efforts with the Empacta and Chimes studies give you a leg up with those action plans?

We’ve been working on advancing inclusive research since 2017, and as we think about the things we’ve done differently, we think about our site recruitment strategy. We think about how we engage with patient advocacy organizations, how we engage with clinical trial research organizations, and we now have in place unconscious bias training to account for study validity. I do feel like we’re better prepared to take these steps. And we’ve been writing articles and sharing it because we don’t want to hold all the secrets. We’re trying to transform society, and we have a responsibility to lead as a founder of the biotech industry.

Is there room for more collaboration in these efforts?

Absolutely. We all need to generate evidence, and a lot of startup biotech companies use the blueprint that we have because they don’t have the same resources. When we do something, it has a ripple effect across the industry.

In these politically divisive times, there’s a lot of backlash against diversity efforts. How do you promote health equity and diversity without getting caught up in the political fray?

We believe in a world where all individuals have access to the best-quality healthcare, and the work we’re doing is to include more people and be more equitable for everyone. Can anyone fault somebody for wanting to ensure people who have a disease actually have a chance to be treated? We’re not thinking about the politics of health equity. We’re thinking about how we ensure all patients have access to innovative clinical therapies and that we’re not leaving patients behind. 

We’re also not blaming patients of color because they don’t have access — we’re thinking about real solutions that can address people’s concerns. It’s not about doing things differently — it’s about doing different things. If we continue with the status quo, then we won’t have the opportunity to treat medically disenfranchised patients. I have a motto that we want to treat every patient like they’re our mother, and if we do that, we’re going to find solutions.