Diversity is a critical component of quality research practices. When a study population does not adequately represent the diversity of the society it serves, one cannot ethically apply the findings to the population at large.
Incorporating patient populations of varying racial and ethnic identities is essential to high-quality research. Learn how drug developers can identify and address barriers to ensuring diversity in clinical research.
Even with a concerted emphasis on attracting a wide range of participants, researchers still struggle to recruit diverse populations. For example, Black participants accounted for 7.7% of US and Canadian clinical oncology trials, but only 2.6% of global oncology drug trials in 2018. Cancer clinical drug trials have become more inclusive of Asian participants; however, other racial and ethnic minority groups remain under-represented. As clinical trials migrate globally, researchers need to make their efforts reflective of, and applicable to, the populations they are serving.
The operative word in clinical trial recruitment is “representative.” If a trial population does not adequately represent the overall patient population for the condition being studied, the trial findings lose relevance. Worse, they can do harm.
Incorporating patient populations of varying racial and ethnic identities is essential to ensuring high-quality research. Other variables factor into a research study’s level of true diversity, including diversity of sex, gender identity, sexual orientation, socioeconomic status, geographic distributions, physical ability, and age. If city-dwellers get over-recruited compared to those living in rural communities, for example, that may significantly impact clinical research outcomes. These two patient populations can differ markedly in their occupational and environmental exposures and, therefore, their disease processes and responses to therapies.
Increasing Diversity in Research
Regulators recognize the disparities inherent in clinical research populations, and they’ve attempted to implement guidelines to augment diversity in clinical trials. In 1993, the National Institutes of Health (NIH) implemented the NIH Revitalization Act, which required that Phase III clinical trials that received NIH funding conduct analyses to ensure that their findings took sex, gender, and race into consideration. An update to this, implemented in 2016 in the form of the 21st Center Cures Act, added increased accountability for researchers—if their trials did not adequately consider women and minority populations, it could jeopardize their future funding.
The importance of diversity in clinical research cannot be understated. Human beings have profound biologic differences and, just as their genes code for different levels of melanin—conferring different skin colors—they also code for different liver enzymes that process drugs, as well as other epigenetic factors.
A person’s race and ethnicity can fundamentally affect their response to a given drug or therapy. Researchers have found that one in five new drugs approved within a recent six-year period yielded differences in response among racial and ethnic groups. In some cases, these differences were so drastic that they necessitated population-specific dosing recommendations.
One can find a primary example of race affecting drug tolerance in the case of Plavix. Post-marketing studies for this blood-thinning medication identified that people with certain alleles of the CYP2C19 liver enzyme poorly metabolized Plavix, rendering it ineffective. People of Chinese background proved to be seven times more likely than Caucasians to be poor metabolizers, putting them at higher risk of fatal cardiac events.
Additionally, the U.S. Food and Drug Administration (FDA) has found that females have between a 1.5 and 1.7% higher risk of experiencing an adverse drug event. The FDA has ultimately withdrawn several medications because of glaring sex-based adverse events.
Barriers to Diversity in Clinical Research
PRA is committed to addressing the following barriers to diversity in clinical research.
1. Hesitance of Participants
Participant hesitancy and skepticism is one of the most significant barriers to increasing diversity in clinical research. Many patients, especially those who are members of racially or ethnically diverse groups, do not trust the research process and are wary of being used as a test subject, potentially even in nefarious ways. Unfortunately, there is precedent for this, as in the historical cases of the Tuskegee Syphilis study—which spanned four decades, ending as recently as 1972—and the prolific stem cell line derived unknowingly from the cells of Henrietta Lacks. In both cases, Black Americans were involved in clinical research against their will, injustices which still resonate within the US today.
Globally, hesitancy in clinical research spread further by dishonorable researchers such as Andrew Wakefield—whose influential British study linking autism and the Measles, Mumps & Rubella Vaccine (MMR) vaccine—got retracted by The Lancet after discovering he did not consecutively recruit his participants as he had claimed. He demonstrated unethical behavior and showed, as described in the Canadian Medical Association Journal, “callous disregard” for the children in his study, upon whom invasive tests were performed.
2. Communication Barriers
As researchers attempt to recruit patients from diverse communities, they must look internally at their recruitment practices. One significant barrier in reaching diverse participants is language-based, as providing translation services adds a layer to a discussion about risks and consent that is already sensitive.
Researchers must ask themselves if they actively advertise their clinical trials to patients who primarily speak languages other than the local country language. Are they looking for patients in places that represent a wide swath of linguistic experience? The digital age provides new opportunities for researchers to extend their reach and communicate their clinical aims.
3. Costs of Participating
Participating in clinical research may impose a burden on a patient’s personal resources, especially their time and money. For example, a rural patient who commits to a clinical trial may need to regularly drive to the nearest study site 100 miles away. This means hours of driving time and associated driving costs every time she travels to the study site. Additionally, participants may need to take time off of work, arrange for childcare, and budget for parking and other expenses.
Many patients cannot undertake the direct and indirect costs of participation, regardless of their level of interest in the trial process. Though there may be reimbursements available, patients may be unaware of them and may preclude their participation. By considering cost and transportation barriers, researchers can minimize in-person site visits and migrate more data collection into the digital sphere.
4. Lack of Clinical Trial Awareness
Lack of clinical trial awareness is one of the most common barriers to clinical trial recruitment. Some researchers describe patients as being stuck in a “pre-contemplation” stage of involvement, in which they have never heard of a clinical trial. For diverse groups to participate in clinical research, they must first have exposure to the concept. The healthcare community as a whole must do a better job at reaching out to patient communities and providing education on how clinical trials work and why patients may benefit from them. Sponsors that work with patient advocacy organizations (PAOs) or physicians and health communities that primarily support diverse populations can reach a wider, more inclusive pool of potential participants.
Promoting Diversity in Clinical Research
One of the most critical steps in expanding diversity profiles in clinical trials is increasing awareness of clinical research among diverse populations. Once achieving sufficient understanding, researchers can further promote diversity by:
- Reinforcing the notion of personal health.
- Ensuring participant safety.
- Providing clear information to participants so that they can make educated decisions.
- Demonstrating appreciation for subject participation.
- Advertising that support is available to participants.
Strategic trial design can also help promote diversity in research. Researchers who studied recruitment of ethnic minorities for mental health trials noted that, unlike the US, many countries with a high amount of ethnic diversity do not have legal requirements in place that mandate inclusion of diverse populations in trial recruitment. These researchers suggest that designing trials that deliberately and proportionally recruit from a country’s minority populations or focusing a research question on those minorities can help overcome these barriers.
The FDA and other regulatory organizations are making progress with their expectations of transparency for both the research community and patients. The FDA’s recent initiative, Snapshots, provides profiles of all clinical drug trials with specific callouts devoted to the diversity of participants involved. These callouts appear fourth in the listing of drug information—in a section entitled: “Were there any differences in how well the drug worked in clinical trials among sex, race, and age?” This explicitness is a significant step in normalizing and emphasizing the importance of diversity in clinical research and will serve the entire research community.
Additionally, the FDA formalized guidance for research teams to help them enhance the diversity of clinical trial populations, with specific descriptions of inclusive trial practices relating to design, eligibility, and reducing the burden on participants.
The bespoke barriers to diversity and developments in diversity promotion ring true for the PRA clinical teams working daily to support patients. By enhancing diversity in clinical trials, PRA hopes to deliver high-quality, personalized, and innovative therapeutics to patient populations who are often overlooked.
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