Diversity and Inclusion in Clinical Trials: Tangible Progress and Strategies for the Future

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The goal within clinical research to improve patient outcomes and ensure that all populations impacted by disease are sufficiently represented is certainly not a new one. However, after its amplification during the COVID-19 pandemic, stakeholders are rethinking how to enhance diversity and inclusion in clinical trials and encourage participation among underserved and underrepresented subpopulations through strategic and intentional patient-centered approaches. In an age of patient partnerships, community-based strategies, and advanced technologies—and with the breadth of data available for deep dives into patient insights—the industry is seeing tangible progress in its efforts to increase diversity and inclusivity in clinical trials.

To achieve meaningful change, the FDA has provided a draft guidance recommending that trial sponsors create a “Race and Ethnicity Diversity Plan” for clinical trials and submit it before finalizing study design and operational plans. Among other parameters, the FDA recommends the plan include enrollment goals and an operational strategy to enroll and retain participants from underrepresented and underserved racial and ethnic patient populations.

A few impactful ways the industry is leveraging insights, experience, and advanced solutions to better implement diversity and inclusion initiatives are noted below.

Earlier trial planning

Traditionally, if diversity was considered, it was at the patient recruitment stage of trials, when it can be too late or too costly. Now, there is a tremendous shift toward sponsors intentionally focusing on sufficient representation earlier in trial design planning and from the outset of trial protocol design when it can make a substantial difference. Clinical research organizations and sites are also designing their study plans to align with sponsors’ diversity goal setting and planning.

Proactive planning and assessing progress of diverse patient enrollment and retention through regular milestone meetings throughout the trial lifecycle are key to improving the ability to achieve diversity recruitment goals, and each stakeholder plays a part. Sponsors can focus on finessing protocol design and their diversity plan, and contract research organizations (CROs) can oversee plan management, including optimizing site selection with representation in mind. CROs also work with sites to enhance recruitment efforts by leveraging data-driven insights, predictive analytics and innovations in technology to fine tune strategies to meet goals for recruitment of diverse patient populations within study timelines.

A deeper understanding of nuances in patient, disease, and geographic location

Strategic diversity planning early in trial design creates an opportunity to incorporate design elements that positively impact the recruitment of diverse patients for a study. Understanding underlying disease epidemiology and incorporating patient demographics and geographical differences in disease outcomes in the real world into the plan can be critical to strategic diversity planning.

In recent years, trial sponsors have increasingly focused on collecting race and ethnicity data and related reporting. From 2016 to 2017, race and ethnicity data reporting from trials via ClinicalTrials.gov doubled from 40% to 80%.

Over time, as race and ethnicity data reporting become more available to leverage via ClinicalTrials.gov and other sources, contextualizing clinical trial diversity data based on disease epidemiology will help sponsors pinpoint where the widest gaps in representation exist and make changes accordingly. Clinical trial sponsors can better design research to represent the diversity of real-world patient populations and nuances that should be considered, given that some diseases disproportionately impact certain racial and ethnic groups.

At-a-glance, diversity data reported over the past decade shows Black/African American participation in Phase II and III trials falls short of 13.6%, the proportion of Black/African Americans in the US population in 2020. However, looking deeper into therapeutic and geographical variations, we can see that for all Phase II and III trials completed in 2020 in the United States and globally, studies in hematology, infectious disease, and psychiatry indications reported Black/African American patient inclusion significantly above 13.6%. But in trials completed for allergy, oncology, or respiratory indications in 2020, Blacks/African Americans represented fewer than 5% of total enrollment, highlighting the disparity and where sponsors should be more strategic and committed to enrolling these patients, because they are burdened by conditions in these therapeutic areas.

Also, a comprehensive clinical development program with diversity goals must account for the intersectionality of drivers of health outcomes and patient demographics. Whether race, ethnicity, gender and/or age, there is a complex mix of drivers that impact health outcomes and create disparities that can vary among demographic groups, including socio-economic status, trust in the healthcare system, logistical barriers to trial participation, genetic and biological differences.

As such, it is critical to gather intelligence about patients’ varying motivations for trial participation by race and ethnicity and the trial design elements that may affect willingness to enroll. Through advanced data-driven methodologies, sponsors can now leverage qualitative patient insights to identify any upfront barriers or considerations, including socio-economic factors that may impact the ability to meet diversity goals.

Committed sites within their communities 

Strong engagement and commitment from those on the frontlines of patient care in trials—investigators and site teams—is fundamental to the implementation of patient-centric recruitment and retention strategies of diverse populations. Sponsors and CROs recognize the importance of working with sites that can engage, recruit, and retain diverse patient populations for their studies.

In some cases, sponsors turn to clinical research site networks to provide dedicated sites within their networks that are successfully enrolling patients from historically underrepresented and underserved populations. These networks include sites located in areas with significant populations of specific racial or ethnic groups and that have an established reputation in these communities of being sensitive to providing a thoughtful and compassionate patient journey for their patients. Key examples of patient-focused site-level support are noted below.

Community outreach

Historical mistrust in health care and clinical trials among traditionally underrepresented and underserved communities cannot be discounted. Respectful communication is paramount for overcoming negative perceptions of clinical research. Sites play a key role in building and establishing trust and connectivity with local patient communities and can help create awareness of trials and related access to treatment.

Sponsors and CROs are building stronger relationships with investigators and site staff from diverse backgrounds who can help study teams reach diverse patient populations for trials. Sites may create local awareness through community events, such as hosting or participating in health screenings, and by networking with community leaders.

Site team members establishing respectful professional relationships with trusted healthcare providers within a community can be integral to referrals of underrepresented patients. The success of the “refer a friend” program, especially at sites with underrepresented racial and ethnic groups, indicates the importance of a patient-centric approach. Sensitivity to a patient-centric trial journey builds trust among community members as the word spreads about the value and positive aspects of clinical trial participation, which can improve trial awareness and recruitment.

Culturally relevant support and communication

Understanding how patients want to receive information and what may help engage them throughout the trial lifecycle need to be an integral part of planning. To identify sites with strong community presence, sponsors should:

• Include sites with staff who have a diversity of backgrounds for stronger engagement with those they serve.
• Identify sites that value and employ diversity- and culture-specific training and educational materials.
• Provide tailored study materials (e.g., patient recruitment and educational information, consent forms, etc.) reflecting the languages of prospective participants to avoid delays in trial activities.

Also, all trial participants potentially have work, family, and community obligations that may conflict with the rigors of clinical trial participation. This may be of heightened importance among patients from underrepresented and underserved groups, who may have less bandwidth to manage some of the inconveniences inherent in trial participation.

Sponsors and sites should remain mindful, anticipating potential challenges and incorporating strategic solutions to reduce burdens when possible. Site management organizations can help sponsors locate sites in areas accessible to or with significant concentrations of underrepresented and underserved populations, including neighborhoods where these patients receive health care. Sponsors can also build protocols with remote visits for patients, such as telephone or electronic data collection, and provide transportation to and from sites when needed.

Defining what “good” means

When taking a closer look at what could help maintain progress, there are several considerations to keep in mind. For one, across stakeholders, aiming to better define what “good” looks like in terms of improving diversity in clinical trials is important.

Because trials differ in size, therapeutic focus, locations, etc., there is no one-size-fits-all approach to this. How do stakeholders gauge progress toward diversity goals for their trials and accurately track, analyze, and report metrics?

Sponsors, CROs, sites, and others need to be specific about their diversity goals for each trial and ensure they are factored into early trial planning, design, and strategy. Sponsors and CROs will want to break down what’s needed to meet diversity goals and how to measure progress.

Ongoing industry dialogue to define what progress should look like will help fine tune individual trials’ goal-setting and related approaches and outcomes analysis. Because the FDA recommends trial sponsors submit plans describing their strategies for enrolling racially and ethnically representative populations in clinical trials, this may produce a stronger frame of reference for future study goals per indication and type of therapy evaluated.

Also, as noted previously, the industry currently has a heightened collaborative mindset, which means more transparency when it comes to sharing trial outcomes. Though information-sharing is beneficial to all committed to improving diversity in trials, stakeholders need to make sure individual trial measurements are not taken out of context. Comparing trial outcomes and progress without cross-referencing patient demographics, geographies, nuances for the therapeutic indication, and other factors can make it difficult to accurately gauge progress in individual programs.

This is another reason sponsors should work closely with regulators to better define measurements for each trial. Achieving representative enrollment, particularly for racial and ethnic minorities in the United States, is both a scientific and fairness issue, and insights gathered could be a differentiating factor with regulators and commercial stakeholders.

An evolving process with commitment

Sufficient representation will always be critical to ensuring drug development efforts adequately improve health outcomes in real-world settings. Continuing to build upon innovative approaches and thought throughout the entire trial lifecycle with intent—from nuances in epidemiology through post-approval market use—has been found to improve trial access for traditionally underrepresented populations.

Looking ahead, diversity and inclusion in clinical trials requires ongoing evaluation and evolved goal setting, but the industry is showing its commitment by creating more efficient and effective pathways to sustainable change for the better.

About the Authors

Leslie Clapp, MD, Vice President, Medical Operations, Avacare Clinical Research Network

In her current role, Dr. Leslie Clapp provides medical oversight and support of Avacare’s 45 sites and more than 200 principal investigators. Prior to joining Avacare, she led a global team of medical researchers as vice president of Medical Services at IQVIA Biotech. Dr. Clapp’s extensive professional experience spans more than 35 years of combined clinical practice and industry experience, including patient care, academia, clinical research, drug development and trial execution. She is a former voting member of the FDA’s Nonprescription Drugs Advisory Committee, where she provided guidance on the safety of changing patient access to medications from prescription to over-the-counter status.

Leslie Henderson-Williams, MA, Director, Global Diversity and Inclusion for Clinical Trials, IQVIA

Leslie has more than three decades of clinical research experience, including extensive work in site management and monitoring and patient recruitment and engagement optimization. In her current role with IQVIA Patient and Site Centric Solutions, Leslie leads efforts to develop, implement and monitor plans to ensure clinical trials are more inclusive and accessible to traditionally underrepresented and underserved populations. For trial sponsors, she aims to help ensure their diversity and inclusion goals align with overall business outcomes.

Dresden Whitehead, Site Intelligence Manager, CCT Research, an Avacare Business

Dresden has 13 years of clinical research experience, heavily focused on patient recruitment for clinical trials in various geographic locations across the U.S. Her work has contributed to advancements in gene therapy, infectious disease and oncology. In her current role as Site Intelligence Manager for CCT Research, Dresden supports data-backed feasibility submissions across the organization’s network of sites.