Clinical trial diversity

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.”

Sponsored content

By SOPHiA GENETICS

BRCA mutations, pivotal in hereditary ovarian and breast cancers, are now recognized for their association with increased risks of prostate and pancreatic cancer. Since the landmark approval of olaparib in 2014, PARP inhibitors (PARPi) have become the gold standard for treating these cancers.

However, meeting the rising demand for testing and analysis poses significant challenges, with the integration of NGS workflows into primary care still lacking. This case study explores BRCA1 and BRCA2 analysis on the SOPHiA DDM™ Platform, showcasing the potential of decentralization to expedite access to critical genetic testing.

I. Decoding risk associated with BRCA mutations

Breast cancer genes BRCA1 and BRCA2 are the genes most commonly affected in hereditary forms of ovarian and breast cancers¹. They are crucial in regulating cell proliferation and supporting normal tissue growth. Growing evidence underscores the connection between BRCA mutations and an increased risk of prostate and pancreatic cancers².

A snapshot of the prevalence and risk of BRCA mutations among different types of cancer.

II. Standard of care for the treatment of BRCA-mutated cancers

BRCA genes play a pivotal role in DNA repair processes, rendering tumors with BRCA mutations exceptionally vulnerable to anticancer drugs that induce DNA damage. If these DNA breaks go unaddressed, it can lead to genomic instability and cell death⁷.

The discovery of the poly(ADP-ribose) polymerase (PARP) enzyme family and its role in DNA repair dates back to the early 1960s and by the 1980s, it became evident that PARP enzymes were not merely crucial for DNA repair but also that inhibiting them held the potential to amplify the cytotoxic effects of specific drugs⁸.

The first PARP inhibitor (PARPi), 3-aminobenzamide, was discovered shortly after7. AS of Q1 2024, several PARPi have been approved:

III. Challenge: Expanding access to timely BRCA analysis

BRCA testing and analysis have assumed a pivotal role in clinical practice, driven by the emergence of FDA-approved PARPi. The importance of assessing its status cannot be overstated, as it empowers healthcare providers to make informed decisions, tailor treatment strategies, and ultimately enhance patient outcomes.

Yet, incorporating BRCA analysis workflows into primary care is not without its challenges, which span various stages of the testing process, including⁸,⁹:

• Precise analysis of ‘noisy’ data from formalin-fixed paraffin-embedded (FFPE) tumor samples.
• Streamlined workflows and real-time communication at the point of care.
• Efficient implementation and scale-up of NGS workflows.
• Access to timely bioinformatic analysis support.
• Gaps in healthcare professionals’ knowledge and training.

Tackling these challenges extends beyond proficiency; it’s about optimizing time and resources. SOPHiA GENETICS addresses these issues through comprehensive training, streamlined implementation, and accelerated BRCA interpretation workflows with the decentralized SOPHiA DDM™ Platform.

IV. Methods: An overview of the SOPHiA DDM™ Platform

The SOPHiA DDM™ Platform is a technology with a dynamic ecosystem, uniting a global community of interconnected users and relying on advanced analytical capabilities, secure decentralized solutions, and streamlined end-to-end workflows. Powered by machine learning and proprietary algorithms, our cloud-based platform standardizes, analyzes, and extracts comprehensive insights from complex NGS data.

As a flexible and scalable platform, SOPHiA DDM™ embraces a rapidly expanding global network of 770+ institutions and 1.5 million genomic profiles, growing by more than 1,000 new profiles every day*. To further accelerate the adoption of NGS into clinical research and practice, we offer robust implementation and deployment programs supported by extensive training and verification. Since April 2018, our team completed over 480 successful programs across more than 270 institutions, reflecting our ongoing mission to democratize precision medicine.

Streamlined sample-to-report workflows for the detection of germline somatic and BRCA mutations in the decentralized SOPHiA DDM™ Platform, gathering NGS data from healthcare institutions to foster collective and global intelligence.

V. Results: A comprehensive look at BRCA footprint in the SOPHiA DDM™ Platform

Over 6 months, the decentralized SOPHiA DDM™ Platform network analyzed more than 69,000 profiles in 40+ countries across the globe using germline and somatic applications encompassing BRCA1 and BRCA2 genes.

Within our global network, the EMEA region comprised 74% of the analyses (over 51,000 profiles), while LATAM represented 11.9% (over 8,200 profiles). This underlines the substantial adoption of decentralized testing and analytical approaches in these regions. Within EMEA, Turkey, Italy, and Spain reported the highest number of analyses, while in LATAM, Brazil, Colombia, and Argentina led the way.

During the same 6-month period, a detailed examination of the Single Nucleotide Variants (SNVs) and Insertion-Deletions (Indels) detected via the SOPHiA DDM™ Platform unveiled a marked prevalence of germline detection within the network, driven by analyses using SOPHiA DDM™ HCS. Specifically, the total count of BRCA1 and BRCA2 mutations identified via germline solutions exceeded that of somatic solutions by 7-fold.

The ratio between potentially pathogenic BRCA variants (identified through BRCA Exchange - version 59¹⁰) and variants of uncertain significance (VUS) per institution was 1:50 in germline applications analyzed through the SOPHiA DDM™ Platform. Conversely, somatic applications showed a more diverse ratio due to their smaller footprint. Thus, for BRCA1 and BRCA2 this ratio was 1:6 and 1:4, respectively.

VI. Conclusion: Take the next step in your precision oncology journey

Timely access to genetic information is vital for managing the risks associated with BRCA mutations. However, the surge in demand often overwhelms centralized labs¹¹, hindering equitable access. Decentralized testing and analysis offers a solution:

• Enhanced accessibility: Testing closer to patients, reducing shipping burdens.
• Local processing and streamlined workflows: Quicker turnaround times.
• Scalability: Flexible expansion to meet growing demands.
• Equitable access: Reducing disparities and engaging communities.

Our decentralized model promotes collaboration and data sharing among testing centers, optimizing resources and providing tailored solutions, fostering a more efficient genetic testing network integrated with centralized labs.

Additionally, our streamlined and expert-led process empowers Pharma and Biotech companies to explore regional and global genetic testing practices for their biomarkers of interest. Developers can use the computational expertise and comprehensive Real-Time and Real-World Data of the SOPHiA DDM™ Platform to expedite the progress of innovative therapies, even those targeting complex and rare alterations.

If you are seeking to harness our expertise, tap into our collaborative network, and explore Real-World Data to propel your precision oncology research with data-driven decisions, we invite you to reach out to our team. Together, we can transform the landscape of cancer care and drive impactful advancements. Contact us today.

References:

1. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2023 Sep 21]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1247/
2. Pilarski R. The Role of BRCA Testing in Hereditary Pancreatic and Prostate Cancer Families. Am Soc Clin Oncol Educ Book. 2019;39:79-86. doi: 10.1200/EDBK_238977
3. Armstrong N, Ryder S, Forbes C, Ross J, Quek RG. A systematic review of the international prevalence of BRCA mutation in breast cancer. Clin Epidemiol. 2019;11:543-561.doi: 10.2147/CLEP.S206949
4. National Cancer Institute. BRCA Gene Mutations: Cancer Risk and Genetic Testing. Accessed on: October 2023. Available from: https://www.cancer.gov/about-cancer/ causes-prevention/genetics/brca-fact-sheet
5. Ataseven B, Tripon D, Rhiem K, et al. Prevalence of BRCA1 and BRCA2 Mutations in Patients with Primary Ovarian Cancer - Does the German Checklist for Detecting the Risk of Hereditary Breast and Ovarian Cancer Adequately Depict the Need for Consultation? Geburtshilfe Frauenheilkd. 2020;80(9):932-940. doi: 10.1055/a-1222-0042
6. Lai E, Ziranu P, Spanu D, et al. BRCA-mutant pancreatic ductal adenocarcinoma. Br J Cancer. 2021;125(10):1321-1332. doi: 10.1038/s41416-021-01469-9
7. Drew Y. The development of PARP inhibitors in ovarian cancer: from bench to bedside. Br J Cancer. 2015;113 Suppl 1(Suppl 1):S3-9. doi: 10.1038/bjc.2015.394
8. Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 2017;18(10):610-621. doi: 10.1038/nrm.2017.53
9. Pace LE, Tung N, Lee YS, et al. Challenges and Opportunities in Engaging Primary Care Providers in BRCA Testing: Results from the BFOR Study. J Gen Intern Med.2022;37(8):1862-1869. doi: 10.1007/s11606-021-06970-8
10. Cline MS, Liao RG, Parsons MT, et al. BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2. PLoS Genet. 2018;14(12):e1007752. doi: 10.1371/journal.pgen.1007752
11. Ionescu F, Zhang J, Wang L. Clinical Applications of Liquid Biopsy in Prostate Cancer: From Screening to Predictive Biomarker. Cancers (Basel). 2022;14(7):1728. doi:10.3390/cancers14071728

*The number of institutions represents active customers who have generated revenue through the SOPHiA DDM™ Platform usage or Alamut™ Visual Plus licenses as of September 30, 2022. The number of profiles refers to those analyzed from December 31, 2021, up to February 2024.

Disclaimer:

SOPHiA DDM™ Diagnostics is for Research Use Only and is not intended for purposes other than research. SOPHiA DDM™ Diagnostics is not for diagnostic, therapeutic, or treatment purposes. All SOPHiA GENETICS trademarks are the property of SOPHiA GENETICS SA and/or its affiliate(s) in the U.S. and/or other countries. All other names, logos, and other trademarks are the property of their respective owners.

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.

Court Horncastle, senior vice president and business unit head of the anti-infective and respiratory team at GSK in the United States, understands the incredible value of diverse teams.

As a U.S. Army Armor Officer leading a tank platoon through the desert in the early 1990s in Saudi Arabia and Iraq, Horncastle’s first tank crew was a living, breathing example of the power and benefits of diversity. Horncastle hailed from the New York City suburbs; his gunner grew up in Puerto Rico; his driver was a “farm boy from Kansas” who’d never left his county before joining the army; and his loader grew up in Compton outside Los Angeles. They had different levels of education and wildly different upbringings and backgrounds.

“You couldn't have taken four more different people and thrown us all together inside a tank where we lived sometimes for weeks, months at a time,” he said.

They also had different worldviews, which meant they could tackle a problem from every angle.

“We were incredibly effective because we were incredibly different,” he said. “Whatever problem or challenge or opportunity that we came across, we had a huge variance in potential solutions because we all started from a different way of problem-solving based on our backgrounds and our experiences.”

Like every industry, pharma and biotech is focused on DEI for many reasons.

“I think diversity, equity and inclusion is incredibly important because I think it's the right thing to do,” Horncastle said. “I also simultaneously think of DEI as a competitive advantage that helps me within the marketplace.”

Unlike other industries, though, the way life sciences companies need to tackle DEI is twofold. Not only are they working on it internally, with their own employees, but they also must work on it externally, by recruiting more diverse groups of patients for clinical trials.

And despite the increased attention on DEI, a report from earlier this year revealed that diversity in clinical trials has actually decreased in recent years. Here are some of the ways companies are refining DEI strategies in the workplace and for patients.

Partnerships and accountability

With the FDA calling for concrete diversity plans and goals in clinical trials, companies are taking action.

“To reach adequate levels of clinical trial diversity, the responsibility lies within the biopharma industry to raise the expectation that DEI is necessary for improved patient outcomes across all therapeutic areas,” said Melaina Boyce, head of in-country clinical study operations in the U.S., Canada and Latin America at EMD Serono, a biopharma company that specializes in infertility, multiple sclerosis and oncology.

For instance, EMD Serono established an internal Diversity and Equity in Clinical Trials Working Group that “created a template to help detail diversity plans when engaging with the FDA about our priority programs,” Boyce said. The template shows the company’s work in understanding underrepresented populations and includes details about how the company plans to attract, recruit and retain these patient populations.

One strategy is partnering with healthcare professionals and community groups.

“Currently, we’re working with trusted partners in the communities,” Boyce said. “Many of these partners — ranging from advocacy groups, to nonprofits, to networks — already have trusting relationships with these audiences, and they can help build a bridge to improve trust and access to these clinical trials through bi-directional communication.”

Other companies are taking a similar approach. For instance, Amgen is funding a nearly $1 million pilot program with The American Cancer Society Cancer Action Network to test a trial eligibility screening intervention intended to increase and diversify patient enrollment in cancer clinical trials. And the Digital Medicine Society launched in February a suite of free resources to advance DEI in digitized clinical trials.

Companies are also holding themselves accountable internally.

“We have put an overarching DEI scorecard in place to monitor metrics and progress across the company, including an area that specifically measures our improvements in clinical trial diversity,” Boyce said. “The scorecard has high visibility within the organization, as global senior leaders evaluate the company’s progress on all relevant DEI items annually. Additionally, the scorecard outlines areas that require action to ensure we’re holding ourselves accountable to the standards we’ve set.”

The Biotechnology Innovation Organization (BIO) is among the organizations focusing on the workforce side. According to interim CEO Rachel King, they’ve just hired a new chief human resources officer, and one of his tasks is to help think through how BIO can help its members with DEI efforts. Although they’ve already started benchmarking around best practices, King said she thinks “there’s a lot more” that could be done and they’re “in the process of defining that.”

People ages 65 and older have the highest rate of chronic disease among any age group — nearly 95% have at least one chronic disease, such as heart disease, arthritis or diabetes, and about 80% have two or more. They are also the heaviest users of medication.

Despite this medical need, clinical trial enrollment of older adults remains low.

In the mid-1990s, fewer than 25% of participants in oncology trials were older adults, even though they made up roughly 67% of new cancer diagnoses and 75% of deaths. Participation in oncology trials among this age group now hovers around 30%, according to Sharmeen Roy, chief strategy and science officer at DoseMeRx, a Florida-based provider of precision drug dosing software.

That’s slowly changing, spurred by an FDA push to boost diversity in trials. The agency issued several guidance documents in recent years aimed at enrolling more adults over age 65, in addition to other underrepresented groups.

But the numbers still aren’t where they need to be, Roy said.

“I think it is improving, but there's room to grow and a lot more that needs to be done,” she said.

A critical demographic

There’s great interest in developing drugs for conditions that disproportionately affect older adults, and nearly 450 of these drugs are in clinical trials. There’s also an incentive to improve care — the cost of managing these diseases is high, making up two-thirds of all healthcare costs overall and 93% of Medicare spending, according to PhRMA.

Drugs often don’t work the same way in this age group as in younger people, Roy said. Older people may take longer to metabolize medications, increasing the risk of toxic reactions at doses that may be safe for someone younger. They may also be on medications that interact with the trial drug, Roy said, rendering many people ineligible.

One blood pressure trial in very elderly adults, for example, looked to assess whether a blood pressure treatment could reduce stroke risk in people over age 80. However, less than 2% of identified patients met inclusion criteria.

While some trials bar older adults based on their health, other exclusions are based solely on age.

“A lot of these older patients get excluded even though they're healthy adults,” Roy said.

These inclusion barriers can limit information about how medications will perform in real-life users, who tend to be older and sicker than people in research studies.

“Oncology medications have a lot of adverse effects and toxicities, so we're not fully understanding how older patients may respond to these therapies and even what may be the appropriate dosing for these patients,” Roy said

The same is true for other types of medication as well. Making enrollment criteria more flexible can help ensure that more older adults are eligible to participate, Roy said.

Inclusion criteria aren’t the only barriers to trial participation. Many older adults simply don’t know that clinical trials are an option due to insufficient outreach, despite substantial interest in taking part. More than two-thirds of older adults said they would sign up for a trial if their doctor recommended it, but research has found that doctors are less likely to offer the clinical trial option to older patients.

Older adults may also need help navigating complex logistical hurdles that may otherwise dissuade them from participating. Many elderly people need assistance from a caretaker to get to the trial site, the lab or imaging appointments. Some sites provide or cover the cost of transportation or adopt a decentralized model, using virtual visits or other strategies to lessen the burden.

“I think that can be helpful if you’re doing outreach specifically for older adults and going to them and making it more convenient,” Roy said.

Clinical trials can be stressful for someone young but are more so for people who are older or in poor health.

“It's a lot for any patient to be in a clinical trial, so you have to almost customize an approach for the elderly population,” Roy said, adding that he had to try novel solutions to keep trials moving during the COVID-19 pandemic.

“I personally had to set up a drive-through pharmacy for my research patients to pick up their medications so there were no missed doses and they could still continue with their visits,” she said. “Sometimes you have to get creative and make sure that they have the resources available.”

Providing ongoing support to patients, particularly when they have burdensome health conditions, can keep people from dropping out.

Proxy problems

Another challenge is informed consent. Those experiencing cognitive decline will need a proxy to sign informed consent forms, but weighing the pros and cons of a trial can be difficult even for those who don’t.

“I have served on a couple institutional review boards and part of the review process is reviewing the consent very closely and making sure that it's at a level where the patient can understand and it's not overwhelming,” Roy said. “That's the goal. You want to make sure they're fully understanding what they're signing up for. Because if they don't, often times you'll see you get the enrollment, they get started and then when they realize what is involved, they’ll drop out. We want to avoid that and make sure that it's truly an informed consent.”

This process should be cognizant of generational, cultural and language barriers.

“In South Florida we have a very diverse population, and we have those challenges and barriers to really understanding the benefits of clinical trials,” Roy said.

In addition to measures taken by sponsors, the push by the FDA will likely continue to increase participation among older adults. Pediatric patients also used to be underrepresented in clinical trials until the FDA pushed for inclusion.

“There were FDA guidance incentives to have those trials,” Roy said. “Now we're at the other end of the spectrum where we have an aging population.”

The country’s population of older adults is growing, so the time is right for change. Some 56 million Americans are over age 65, and that number is expected to climb to 80.8 million by 2040.