Inclusive Trials, Informed Treatments: Prioritizing Diversity in Clinical Research

Credit: Unsplash / Matheus Ferrero

The lack of diversity in both clinical trials and healthcare providers creates complex challenges across the industries of practice and research. Disparities such as the disproportionate number of White providers lead to a mismatch in cultural understanding and trust among diverse patient populations. This also extends to clinical trials, where an historical mistrust among minority communities and unequal access to healthcare providers limit recruitment and participation and, in turn, hinder research outcomes. Language barriers further complicate communication between patients and providers as well as access to care.

This lack of diversity not only affects research outcomes, but it also limits the understanding of disease manifestations and treatment responses across different populations.

Strategies designed to improve health equity and enhancing transparency—involving diverse healthcare providers and advocates—are critical steps towards promoting inclusivity and diversity in healthcare and research practices.

Lack of Diversity in Healthcare Providers and Clinical Trials

Across all medical indications, clinical research has historically been driven by North American and Western European countries, and predominantly involve White male populations in trials. The conventional teaching and understanding of diseases is therefore based on these populations.

Unfortunately, trials do not recruit participants who represent those most affected by a particular disease. Lupus, for example, is 3 times more prevalent in Black women compared with White women.¹

Due to this exclusion, “we don't have as much information about how lupus affects a larger, more diverse population of patients,” Ashira Blazer, MD, MSCI, assistant professor in the University of Maryland Division of Rheumatology, told HCPLive.

This underrepresentation is also mirrored in the lack of diversity among health care providers which, of course, does not reflect the diversity of the general population.

“Our health care providers don't adequately represent the patient population,” John H. Stone, MD, MPH, professor of medicine at Harvard Medical School and a rheumatologist at Massachusetts General Hospital, told HCPLive. “A majority of our health care providers are White, and while we are seeing more women entering the healthcare field, the profession still remains predominantly Caucasian.”

To combat this, increasing the percentage of minorities in healthcare is crucial. An influx of a more diverse population of providers could help patients feel more comfortable with their healthcare choices and accessing novel treatment approaches.

Organizations like the Arthritis Foundation offer Diversity, Equity, and Inclusion (DEI) awards to increase the number of specialists and support the training of a diverse generation of rheumatologists. These awards are designed to address disparities in patient care and outcomes with a focus on attracting historically underrepresented medical students and residents to rheumatology.²

Historical Mistrust and Access Barriers

The lack of diversity in clinical trials stems from multiple factors. In the United States, there's a historical context of medical distrust among communities of color due to past unethical practices and disparities in healthcare access. This skepticism extends to clinical trials, where there's often a perception of minority groups being used as "guinea pigs" or not receiving the same level of care as others.

“I think there is a bias amongst people of color to not trust that participating in a clinical trial is in your best interest,” Judith Ng-Cashin, MD, chief medical officer at Novotech, told HCPLive.

The most famous example of this is the US Public Health Service (USPHS) Untreated Syphilis Study at Tuskegee, which was designed to record the natural history of untreated syphilis. Starting in 1932, researchers enrolled 600 Black men (399 with syphilis and 201 without). The men did not give informed consent, and in exchange for their participation they were given free meals, free medical exams, and burial insurance.³

By 1943, penicillin was becoming widely available and was considered the treatment of choice for this condition. However, over the course of the 40-year federal experiment, the men involved in this study were not offered this treatment and were left untreated for decades for research purposes.³

According to a survey conducted by Kennedy et al., this underlying mistrust between poor and minority populations is also due in part to previous negative experiences with the health care system which can also impact recruiting for clinical trials.⁴

“The healthcare system has not been trustworthy for all people,” Blazer said. “We know that there are big historical ills and I think many people are aware of those. But then also in the day-to-day when patients, particularly those of ethnic backgrounds that face heavy discrimination, see their physicians, they're not being treated the same and they're not being offered the same things.”

Another factor is the unequal distribution of healthcare providers across the country.

“The distribution of health care providers is in the country is not done in an equitable way so that minorities have equal access to healthcare providers and to clinical trials and cutting edge studies that are going on,” Stone added.

The Arthritis Foundation has introduced fellowship programs to help the approximately 60 million Americans are living with clinically diagnosed arthritis get access to care. This strategy focuses on expanding the number of fellowship opportunities for rheumatologists, with an emphasis on communities facing the most significant shortages.⁵

Need for Language Accessibility

Language barriers are also a hinderance to patient-provider communication and access to healthcare services.

Stone explained one important way to enhance diversity and participant recruitment for trials is language accessibility. To better serve his patients, he is currently learning Spanish as he believes it is increasingly important for American healthcare providers to be able to communicate with patients in their preferred language. He also encourages consent forms to be available in multiple languages.

“Healthcare providers, healthcare systems, and hospitals need to have adequate representation of translators and translating facilities, which can even be web-based, to bridge language barriers,” he added.

Importance of Inclusive Clinical Trials

Inclusivity in clinical trials is essential to understand disease presentations and treatment responses across diverse populations.

“Our population is a diverse one—a melting pot, right? So, if we're unable to get patients of all backgrounds in our clinical trials, then we're not going to be able to find appropriate solutions,” Blazer said.

In rheumatology, the lack of diversity in clinical trials presents significant challenges for several reasons. Diseases in rheumatology, such as lupus, affect diverse populations differently, yet clinical trial participants often do not represent this diversity.

“Patients with lupus also have symptoms such as pain, depression, and fibromyalgia, can't be as closely tied to the inflammatory conditions—those are very difficult to treat,” Blazer explained. “Also, the way that people express their symptoms tends to be tied to their culture. And so, it's difficult to understand how a wider variety of patients experiences those symptoms and what we do about it.”

In her research regarding health disparities in systemic lupus erythematosus (SLE), Blazer and her team examined the relationship between self-reported race and ethnicity and disease outcomes. They found that—as race and ethnicity are social taxonomies as opposed to biological determinants—differences in severity and outcomes observed across racial and ethnic groups are largely due to the differences in access to care opportunities to achieve optimal health.⁶

This lack of access leads to gaps in understanding how treatments affect various patient groups and limits the ability to tailor treatments effectively. Limited diversity in these trials ultimately leads to a limited understanding of disease manifestations and treatment responses across different populations. This makes it challenging to develop medications that effectively address the needs of diverse patients.

“Not only is it harder to recruit patients when you can only recruit from a small subset, but it's also harder to understand how the different phenotypes that we see in rheumatology could respond to certain medications,” she explained.

When considering timing issues and other opposing factors, Blazer acknowledges drug companies face pressures to enroll specific types of patients in clinical trials. They prefer patients with manageable symptoms, good access to care, health literacy, and few comorbidities or pain.

“That criteria are not often met by people who are underserved and underprivileged in medicine because those patients have worse disease, those patients don't have access, those patients can't get to the doctor very quickly, etc,” she said. “All of those complications are going to influence the trial outcome.”

Consequently, trial outcomes may not accurately reflect real-world patient experiences, and drugs may be approved based on limited data from a less diverse patient pool, which can slow down the pace of research and impact the development of potentially effective treatments.

“A driving factor of wanting to be more inclusive and promote diversity in these trials is to better understand the scope of what the disease looks like, and what we should target,” Ng-Cashin said.

Additionally, the settings where these trials occur, often large academic centers, are not easily accessible to underprivileged populations, further exacerbating the issue. This highlights a systemic issue where those already failed by healthcare systems are further disadvantaged in clinical research, creating a cycle of inequity.

However, there is a growing awareness in the clinical trial landscape that researchers need to broaden their view of diseases and how they presentation across diverse populations. Conditions like lupus highlight the importance of inclusivity in research to capture a more comprehensive understanding of diseases and their impact.

Building Trust and Education

Creating trust within minority communities and educating them about the importance of clinical research are key strategies to overcome barriers, address biases on both the investigator and participant sides, and enhance diversity in clinical trials. Engaging with community leaders and providing culturally competent care are vital steps toward inclusivity and representation in healthcare research.

To overcome these challenges, Blazer emphasizes the importance of strategies like community engagement, partnering with trusted leaders, and providing education about the importance of clinical research are essential. These efforts aim to address biases and build rapport to ensure a more inclusive and representative participant pool in quality trials.

“I think we are starting to make progress by partnering with people within the community to facilitate that trust that has been lacking in the medical establishment,” she added.

To foster inclusive and representative research practices, improving health equity and access to clinical trials is essential, as patients who lack consistent care are often not included in trials.

“People who can't have access to health care can't have access to clinical trust,” Blazer said. “The reason why a lot of patients aren't able to be enrolled is because they don't have consistent care. And even if they do have consistent care, the thought that they'd be able to, for example, be a part of a trial and go to a follow-up visit every 3 months or so is not feasible for those patients.”

Additionally, transparency in research practices and trustworthy, culturally competent care are vital to building patient trust and engagement. Increasing diversity among healthcare providers and involving non-physician providers in trials can also help bridge the gap and ensure trials reflect the diversity of the patient population.

“The path to making the physician population more diverse is going to be a long one,” Blazer said. “But I think that we can also engage allied health professionals and other patient advocates who can help educate around clinical trials and help be a part of that infrastructure that gets people in.”

Ultimately, a collaborative effort across healthcare systems, research institutions, and communities is needed to address these challenges and promote inclusive research practices in rheumatology and beyond.

References

1. ^{Lupus: Hard to diagnose, disproportionately affects black women, but fairly little known in the community. MSBWR. Accessed May 4, 2024. https://msbwr.org/lupus-hard-to-diagnose-disproportionately-affects-black-women-but-fairly-little-known-in-the-community}
2. ^{Diversity, equity & inclusion initiatives. Science & DEI | Arthritis Foundation. Accessed May 7, 2024. https://www.arthritis.org/science/focus/workforce-development/dei.}
3. ^{Public Health Service study of untreated syphilis at Tuskegee and Macon County, al - timeline - cdc - os. Centers for Disease Control and Prevention. December 5, 2022. Accessed May 7, 2024. https://www.cdc.gov/tuskegee/timeline.htm.}
4. ^{Kennedy BR, Mathis CC, Woods AK. African Americans and their distrust of the health care system: healthcare for diverse populations. J Cult Divers. 2007;14(2):56-60.}
5. ^{Fellowships. Science Fellowships | Arthritis Foundation. Accessed May 8, 2024. https://www.arthritis.org/science/focus/workforce-development/fellowships.}
6. ^{Parodis I, Lanata C, Nikolopoulos D, Blazer A, Yazdany J. Reframing health disparities in SLE: A critical reassessment of racial and ethnic differences in lupus disease outcomes. Best Pract Res Clin Rheumatol. Published online December 5, 2023. doi:10.1016/j.berh.2023.101894}