Embracing Diversity: The Imperative for Inclusive Clinical Trials

Patient waiting in waiting room filling out paper work.

Most new medications are developed following a series of clinical trials. The most advanced, Phase III studies are designed to assess both safety and efficacy or whether a drug works in a large population – ideally, one that includes a diverse group of people. Unfortunately, most trials lack a range of diverse trial participants.

“When developing a new drug, researchers need to make certain that the population enrolled in the clinical trials represents the type of population that the drug is going to be used in,” says Ajay Singh, MBBS, FRCP, MBA, senior associate dean for postgraduate medical education at Harvard Medical School and faculty director, Global Clinical Scholars Research Training certificate program. That means that trials should ideally recruit minorities.

According to the US census, the US population today includes 30-40% minorities: about 14% African-Americans, 19 % Latino or Hispanic, and 6% Asian, with a smaller percentage of indigenous Americans of less than 2%.

However, a recent analysis of 32,000 individuals who participated in new drug trials in the US in 2020 showed that only 8% were Black, 6% Asian, 11% Hispanic and 30% were age 65 and older, showing relative underrepresentation of these important demographic groups. The study authors suggest these estimates have worsened since 2019. In Singh’s view, the ideal scenario involves recruiting 30-40% minority participants for inclusion in a clinical trial to match the population.

Why Inclusivity Matters

The lack of diversity in clinical trials can have significant consequences for public health. If they only include participants from a narrow demographic group, the results may not accurately represent the broader population. This can result in drugs and treatments that are less effective or even harmful for certain groups of people.

As a recent high-visibility example, diversity emerged as an issueduring the trial of Moderna’s Covid-19 vaccine. When it was reported that Black Americans represented only 7% of the trial versus 13% of the US population, the company slowed the trial to recruit more people of color as trial participants.

Drugs May Work Differently Depending on Ancestry

One example includes the use of cardiovascular medications, which have been documented in the medical literature to produce clinical differences between white people of European ancestry and African-Americans. Several clinical trials have shown varying responses to the blood pressure-lowering effects of β-blockers and ACE inhibitors, among others. Over time, these differences in response became well accepted, such that ethnicity began to be used in helping to guide the selection of antihypertensive drug therapy.

“An individual’s genetic background translates into how drugs may work,” says Singh. Indeed, the whole field of pharmacogenomics centers on how an individual’s genes affect how they respond to medications. “This can mean that different drugs may work differently in different racial subgroups.”

Government Organizations Demand Testing Inclusivity

As a practical matter, governmental organizations like the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) require diversity inclusion.

FDA legislation insists on recruiting a diverse population for testing a drug. In an updated 2020 advisory, the FDA recommends different approaches that sponsors of clinical trials for a new drug can take to increase enrollment of underrepresented populations in their clinical trials. For pharmaceutical companies seeking FDA approval, getting the drug approved by the FDA may be difficult if the clinical studies are not representative of all ethnic groups. And it’s not good enough to say you tried, according to Singh. 

The National Institutes of Health (NIH) recommends that studies should define goals for the recruitment of underrepresented clinical trial participants. In addition, since the 1993 National Institutes of Health Revitalization Act, NIH has required researchers seeking grants to include women and minorities in NIH-funded studies.

“If a project is to be funded by the NIH, the grant proposal needs to demonstrate how a diverse sample of subjects will be recruited,” adds Singh.

Factors Contributing to the Lack of Diversity in Clinical Testing

To make a successful case for inclusion in a clinical study, minority participants may want to know whether the drug has been studied in their ethnic group. “You will want a diverse population so that you can ultimately make that connection,” adds Singh.

But several factors interfere with making those connections.

Some groups may distrust healthcare settings

The healthcare system has a troubled history of mistreatment of minority groups. The Tuskegee Syphilis Study is perhaps the most well-known and created a legacy of mistrust and suspicion toward healthcare providers. “Almost everybody looking at it with hindsight thinks that it was inappropriate and unethical behavior,” says Singh. “The consequences from Tuskegee have been devastating because it generated a lot of distrust among the African-American population.”

To acknowledge the damage done by this study, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued the Belmont Report in 1979, which established principles for research involving human subjects – respect for persons, beneficence, and justice – to make sure a Tuskegee-type study would not happen again.

Provider Perceptions and Language Differences

Healthcare professionals may hold unconscious biases that affect how they interact with patients. This can result in differential treatment, lower quality of care, and poorer health outcomes for minority patients. Also, some providers may be unaware or insensitive to the cultural norms and values of minority groups which makes building trust difficult.

“There are many studies that have shown that there seems to be negative biases against African Americans and Latinos in receiving access to care, and that may extend into biases against recruiting them in trials as well,” says Singh.

In addition, language barriers can make it difficult for patients to understand their medical conditions and treatment options, complicating communication. This can lead to misunderstanding the research's significance and mistrust in the consenting process.

Lack of Access to Healthcare

Minority communities may have limited access to healthcare facilities and services due to economic influences, contributing to the lack of inclusivity in clinical trials.

“You are not easily able to participate in clinical trials if you are working 9-5 and taking public transportation,” says Singh. “And if you’re not getting your basic clinical care because you aren’t seeing doctors frequently enough, you may not get access to information about clinical trials.”

Strategies for Improving Diversity

A report from the Harvard Business Review suggests recruiting patients from independent disease registries. Another strategy is to go beyond academic medical centers for potential participants, such as local health systems, community organizations, and even direct-to-consumer through social media and traditional media outlets.

Singh believes the first step is increasing awareness among clinical researchers of why it’s important to enroll a diverse population besides the issue of the requirement from a regulatory perspective.

The second priority involves creating a counter-narrative to build trust during the recruitment process.

“Of course, the role of the ethics committee is important,” Singh explains. “They work towards making sure that a trial is safe and that any potential risks are explained in the consent form. However, the ethics committee also provides guardrails to the principal investigator in emphasizing the recruitment of a representative population. That said, community outreach shouldn’t be forgotten by the principal investigator as a means to build trust during the recruitment process”.

Last, Singh strongly encourages providing appropriate incentives for potential trial participants to encourage the recruitment of a diverse population. Examples include paying for local transportation costs, meals during the times participants are at a testing facility, and parking.

  • References

    U.S. Census Bureau quickfacts: United States. (n.d.). https://www.census.gov/quickfacts/fact/table/US/PST045222



Program Type

Related Articles