The Importance of Inclusion & Diversity in Clinical Trials

Inclusion and diversity have always been important, but there has been a renewed focus on them in clinical trials in recent years. From initiatives to recruit more women and people from racially diverse backgrounds, to promoting a conscious effort to include differently-abled people, there is plenty the industry can do.

While the two terms are often used together, they are not the same. Diversity refers to the variation of personal, social, and physical characteristics, while inclusion describes how places provide access to people with different characteristics. In other words, diversity is the “what” and inclusion is the “how”.

In this article, we’ll discuss the importance of diversity in clinical trials and how more clinical research teams can improve diversity and inclusion in clinical trial participant recruitment.

What does diversity mean in clinical trials?

Diversity in clinical trials means ensuring there is a diverse range of participants included throughout the trial. The safety and efficacy of medications and vaccines can differ depending on a variety of factors, which is why it’s important to include a wide representation of different people.

Some factors for consideration include:

• Age
• Ethnicity
• Race
• Gender
• Sexual orientation
• Geographic location
• Socioeconomic background
• Disability
• Health status

What does inclusion mean in clinical trials?

As previously mentioned, inclusion is the “how” that drives diversity in clinical trials. It is what ensures diverse groups of people are included in the clinical trial. When specifying the criteria needed for a research group, researchers will need to consider inclusion and ensure a diverse range of groups are included for the best results.

Why is there a lack of diversity in clinical trials?

There has been a lack of diversity in clinical research for some time, and while it’s improving, there is still more to be done. In 2020, 75% of clinical trial participants were white, 11% Hispanic, 8% black and 6% Asian, according to Food and Drug Administration data.

Clinical trials have not always recruited the participants who best represented the individuals affected by the disease, condition, or behavior being studied. Relying on exclusively male participants, for a variety of reasons, resulted in gaps in our general understanding of diseases and conditions.

Some of the reasons for a lack of diversity include:

• Fear
• Mistrust of the clinical research process
• Participation stigma
• Lack of understanding of the value clinical research can provide
• Negative opinions of friends and family members
• Perceived financial burden
• Unwanted time commitment
• Problems with transportation
• Inaccessibility
• Lack of awareness about clinical trial availability

Why is diversity and inclusion in clinical trials so important?

Clinical trial diversity is hugely important for a variety of reasons. The main reason is to ensure all communities around the world can benefit from advances and revelations in science and research.

Different groups of people may experience the same disease, condition, or illness differently. And some of those people will have different side effects to medication. It’s therefore essential that clinical trials include a diverse selection of participants with different lived experiences, living conditions, and characteristics such as age, gender, and race.

By ensuring there is a diverse pool of people included in a clinical research group, researchers can gain a greater volume of valuable information. For example, including participants from a wide variety of ethnicities means improvements can be made to the development of medicines and vaccines for everyone.

Diversity in clinical trials is also vital for research equity and building trust in clinical research. This is especially important for groups who may have historically been underrepresented or had trust issues with clinical research.

Factors that create clinical trial diversity

There are many factors that can affect the risk or likelihood of developing certain conditions or diseases. These factors can also influence the chance of a person experiencing a long-term health outcome or how someone responds to treatment.

Each of these factors contributes to the need for diversity in clinical research. These include, but are not limited to:

• Age
• Biological sex
• Race
• Ethnicity
• Sexual orientation
• Pregnancy status
• Life experiences
• Unhealthy behaviors
• Health-promoting behaviors
• Environmental conditions
• Genetic variation and geographic ancestry
• Underlying medical problems or the presence of comorbidities

Benefits of diversity and inclusion in clinical research

A key benefit of including minorities in clinical trials is improved access. Greater diversity in clinical research means the results can be generalized for wider populations, helping to deliver equal access to new treatments. When the results are true for a wider selection of people, there will be better access to successful medications and an improved understanding of the impact certain diseases or conditions can have.

Clinical trial diversity can also reduce health disparities among underrepresented populations by ensuring people from those backgrounds have been included in the research. This has the potential to reduce social inequality and social disparities in both health and healthcare.

Finally, including people from all walks of life with different characteristics gives researchers the opportunity to improve their understanding of the safety and efficacy of potential drugs or vaccines. They can monitor the effects of these drugs on different people to see how they are affected and make changes to improve it for those groups.

Challenges in achieving diversity and inclusion in clinical trials

Diversity and inclusion rates have varied significantly over the last decade, making it clear that there are still challenges to achieving diversity and inclusion. Some of these barriers include trial availability, eligibility and access. However, other challenges include more societal issues such as negative beliefs, norms and attitudes.

Medical mistrust, particularly in the USA, continues to be the biggest challenge in achieving inclusivity and diversity. Many groups lack trust in the healthcare system for varying reasons, resulting in low numbers of participants from those groups. For example, American Indians and Alaska Natives make up just 1% of participants in NIH clinical research studies.

Some of this can be put down to a historical mistrust by Native Americans in clinical research. In the early 1990s, DNA samples from members of the Havasupai Tribe were given to Arizona State University for a diabetes research study. It was later discovered that this DNA had been used for additional research on ethnic migration, schizophrenia and inbreeding.

The Havasupai Tribe filed a lawsuit in 2004 stating they had not given informed consent for the additional use of the samples. The lawsuit was settled in favor of the Tribe in 2010, but mistrust still remains.

This mistrust, and that of similar experiences, continues to be a challenge for clinical researchers. Ultimately, many diverse groups in America do not trust the healthcare ecosystem. Unfortunately, this will only continue to result in poor health among these populations.

What happens to clinical trials without diversity and inclusion?

Without diversity in clinical trials, results will never be applicable to everyone. This is a problem because it leads to health disparities and a lack of understanding or research among particular groups. A lack of diversity also means a risk of collecting insufficient data to assess effectiveness or safety in particular populations.

For example, an underrepresented group given medication for a condition that has been mostly trialed on another group may not respond as effectively. Additionally, mistrust among underrepresented groups may increase as they learn that they are not being represented effectively in clinical trials.

How to increase diversity in clinical research

There are several things research teams can do to increase inclusion and diversity in clinical trials. These range from working with organizations to reaching and building trust within diverse communities, to offering hybrid trials where participation access and convenience are improved.

Choose sites near target communities

We know that convenience and access can be barriers to participation for some groups. Research teams should select study sites that are centrally located and close to the communities they are targeting.

If the study is targeting a larger number of people and needs to include several diverse groups, choosing multiple sites across different geographies can help to improve access.

Offer hybrid participation options

If a particular study is aiming to appeal to a more diverse population, researchers need to carefully consider their barriers to participation. One way to combat barriers is to offer a hybrid approach whereby participants can be involved via both face-to-face and virtual or remote elements.

Work with organizations that can reach diverse communities

There are several groups that specialize in clinical trial diversity support and reaching minority communities. Partnering with these organizations can help to include a more diverse range of participants in a study. For example, Egality Health is just one organization that is working to address health inequalities in clinical research.

Build trust among participants and researchers

We’ve already mentioned how trust is one of the biggest challenges when aiming to achieve diversity in clinical trials. Researchers should target this challenge head-on to improve diversity and inclusion. They can do this by understanding where the mistrust comes from, both previously and today. From here, they can work with diverse groups to learn how to improve and gain trust.

Use marketing that resonates with diverse populations

Marketing plays a big role when it comes to recruiting participants for clinical research, and it can be a valuable tool for reaching diverse groups of people. Online, researchers can target specific audiences by implementing location-based ad targeting, using imagery that reflects the group, and leveraging data to attract clinical study participants.

What are research teams already doing to improve diversity and inclusion?

While the aforementioned tips can help research teams improve their diversity and inclusion efforts, there are plans already in motion by clinical research groups alongside legislation that aims to improve diversity and inclusion.

For example, the Equality Act prohibits discrimination based on sex, sexual orientation, and gender identity in areas including public accommodations and facilities, education, federal funding, employment, housing, credit, and the jury system. The Equality Act holds clinical research teams accountable and encourages them to improve diversity.

Additionally, the Inclusion Across the Lifespan (IAL) policy was created in 2019. This requires NIH-funded studies to include individuals of all ages (including older adults and children) in clinical trials unless age-based exclusions are scientifically or ethically justified. 

Technology also has the ability to improve clinical trial research and address health disparities among communities. Researchers can use new advances in technology to make trials more accessible, engaging and informative for participants, while also receiving better quality data and insight.

Real-world examples of the need for inclusion in clinical trials

It’s fair to say that clinical trials have previously failed in the diversity and inclusion stakes. However, there are several examples of where greater inclusion and diversity was needed in clinical trials, with researchers able to lean on this information to improve their future efforts.

COVID-19 and race

There is much to be learnt from the COVID-19 pandemic, particularly in relation to racial and ethnic minority populations, including African Americans, Hispanics/Latinos, Native Hawaiians, American Indian/Alaska Natives and Pacific Islanders. At the beginning of the pandemic, COVID-19 disproportionately affected these groups, with increased cases, hospitalizations and deaths.

Because of this, COVID-19 vaccine trials needed to include representation across diverse groups to better understand the effectiveness of vaccines among minorities. Additionally, this inclusion was important due to the historical lack of mistrust and exclusion of these groups.

However, the results of some COVID-19 vaccine trials still showed racial disparities. In the Pfizer BioNTech mRNA vaccine study, just 3-9% of participants were black or African American, and only 1-8% were Asian. 

COVID-19 and pregnancy

‘Protection by exclusion’ has been prominent in clinical trials for some time, and this was no different when it came to excluding pregnant and lactating women from COVID-19 vaccine trials. Additionally, the World Health Organization recommended that pregnant women should not get a vaccine, leading to further vaccine hesitancy.

Out of 90 vaccine trials, 97.8% excluded pregnant women from participation. This resulted in vaccine hesitancy among this group despite the fact that pregnant women with COVID-19 were more likely to be admitted to intensive care than women of childbearing age who were not pregnant. Additionally, stillbirth was a recognized complication of COVID-19 in pregnant women, caused by SARS-CoV-2 infection of the placenta.

Data later revealed that COVID-19 vaccines were safe for pregnant women. Sadly, the damage had already been done by the time this information was available, and many women had not been vaccinated.

Alzheimer’s and race

Older black Americans are twice as likely than older white Americans to have Alzheimer’s or another form of dementia, while Hispanics are one and a half times more likely. This information should mean that more African Americans and Hispanics are included in Alzheimer’s research to ensure suitable treatments can be found. However, racial diversity in clinical trials has not always been a focus.

In a phase 2 trial of an Alzheimer’s drug with a large geographic footprint, 97.5% of the participants were white and only 2.8% were Hispanic. This shows a clear disparity between the participants included in the research and those more likely to suffer from the disease, making research findings less applicable to minority groups.

Asthma and socioeconomics

There are several causes of asthma, many of which are complex and depend on a variety of factors. In the US, asthma is suffered disproportionately among black and American Indian/Alaska Native people. Studies have shown that these groups have high rates of asthma, and related deaths and hospitalizations.

Some of the factors contributing to these disparities include:

• Socioeconomic status
• Neighborhood and physical environment
• Systemic racism, segregation and discriminatory policies
• Social support networks
• Access to healthcare
• Education level
• Employment status
• Genetics and ancestry
• Behavioral determinants like tobacco and medication use

Social determinants and structural inequalities are often bigger drivers of asthma disparity than genetics and individual behaviors. It’s crucial that clinical trials related to asthma include people from the minority groups more likely to suffer from it.

The future of diversity and inclusion in clinical trials

In recent years there has been a renewed focus on clinical trial enrollment and diversity, and the benefits this can provide.

We’ve already mentioned some of the legislation in place to improve inclusion and diversity in clinical research, but there is more to be done. In 2020, the FDA issued a guidance titled “Enhancing the Diversity of Clinical Trial Populations - Eligibility Criteria, Enrollment Practices, and Trial Designs for Guidance and Industry” to address the need for enhanced diversity in clinical trials. This guidance encourages research teams to promote diversity in clinical trials by modifying eligibility criteria, enrollment practices and trial designs. 

It also seeks to encourage people with disabilities to enroll in clinical trials. Frequent visits to trial sites can be problematic for individuals who rely on caregiver help or transportation. Therefore, the FDA has also proposed measures including reduced visit frequency, virtual or hybrid options, and making participants aware of reimbursements for travel and accommodation expenses for trial participation.

The Bottom Line

Inclusion and diversity in clinical trials are key for the future of clinical research. We believe research teams will seek to improve diversity efforts further to provide equal health for all communities, produce more robust data, and ultimately be able to deliver treatments that work for all.