Diversity in Clinical Trials: Strategies and Challenges

Jamie Harper, MHA, CCRP, Vice President, Site Solutions and Engagement, WCG

The importance of diversity, equity, and inclusion (DE&I) within clinical trials continues to be a topic of discussion across industry conferences, within healthcare organizations, and among healthcare providers and patient advocate groups. While the general intent of DE&I may be understood, the concept can take on a different meaning when informed by individual cultures and experiences. Before DE&I strategies supporting participant recruitment, engagement, or retention can be developed or challenges addressed, a common baseline understanding of what DEI means is required.

Understanding DE&I

A fundamental challenge with DE&I is truly understanding what it means. DE&I is often discussed as a bundle, or “diversity” is used as an umbrella term for DE&I. However, each word included in this acronym, diversity-equity-inclusion, represents a distinct value that should be considered when developing clinical trial recruitment, engagement, or retention strategies.

The National Institute on Minority Health and Health Disparities (NIMHD) succinctly summarizes diversity in clinical trials as ensuring “people with a variety of lived experiences and living conditions” participate “so that all communities can benefit from scientific advances.” Essentially, diversity refers to the traits and characteristics of people, such as race, ethnicity, age, and sex.

These factors can have an impact on how a drug is metabolized, the efficacy of the treatment, and even the safety of the medicine being tested. Other factors, such as nationality and physical ability, should also be considered when developing protocols for diverse population enrollment.

It may prove difficult to consider every minor dimension during trial protocol and study strategy development, but successful strategies include monitoring these aspects when identifying potential study participants.

While diversity focuses on traits and characteristics, “equity” refers to providing equal access to the same opportunities. Understanding diversity helps us understand equity. Equity ensures that clinical trial opportunities are provided in such a way that all populations, especially those who are underrepresented or disadvantaged, can participate.

Participants in clinical trials should represent the population who are most likely to have the health condition being investigated, which, in turn, helps support diversity. For example, a participant’s financial status or geography may impact their ability to follow a specific visit schedule.

If a study site is not easily accessible because it is in a rural community, an unstated inclusion criterion becomes the availability of transportation. If an individual does not have private transportation or the ability to utilize public transportation, they have effectively been excluded from the study even if they met all the other criteria outlined in the protocol. While the opportunity to participate is available, lack of access to the opportunity creates the inequity. Likewise, a study’s site selection can have an unintended impact on equitable participation if the sites selected are not within reasonable travel range of an underrepresented patient population.

It’s these unstated criteria that cause unforeseen restrictions in a population’s ability to participate in clinical research.

When diversity and equity in clinical trials are considered appropriately, inclusivity should inherently be addressed. Where diversity refers to traits and characteristics of people, “inclusion” refers to behaviors and practices. These are often referred to as social determinants of health (SDOH). The World Health Organization defines SDOH as “the conditions where people are born, grow, live, work, and age.” They can include such factors as education, employment, housing, and access to healthcare.
SDOH have a significant impact on an individual’s ability (and willingness) to participate in clinical research. As mentioned with equity, unstated eligibility criteria can also impact inclusion in clinical research due to SDOH factors.

In another scenario, a protocol investigating a new cancer treatment may require a significant number of blood draws throughout the week, requiring frequent visits to the research site during the day. A patient who meets all the criteria and is willing to enroll may decline study participation due to a work schedule that doesn’t allow for the required time off.

When developing a clinical trial protocol, it is difficult to account for every possibility that may knowingly (or unknowingly) impact participant recruitment, engagement, and retention. However, it is easy to see how neglecting one component of the DE&I acronym has a compound effect on the other components.

Developing a successful study strategy includes consideration of all DE&I components at the research site and sponsor level.

Looking beyond the I/E criteria for DE&I-focused recruitment

When strategizing a clinical trial recruitment plan, the contribution potential of each research site should be determined based on the study goals and timeline. Proactively identifying barriers to study recruitment should include an assessment of any unstated eligibility criteria.

A quick glance at the inclusion/exclusion criteria will provide an estimate of potential participants in the targeted population, but not necessarily a true representation of their enrollment contribution potential. Looking past the stated criteria and identifying the unstated criteria can assist research sites in advocating for potential participants prior to study activation.

Ensuring there is assistance for securing transportation or transportation costs in a rural community setting can help prevent declines in study participation and reduce dropout rates.

If a study protocol involves patient-reported outcomes that require the use of a smart phone, understanding the catchment area can help determine whether smart phones may need to be provided for the target population. Instructions on how to use the device may also need to be included in the study requirements.

Assessing the unstated criteria when first considering activation of a new protocol can help guide proactive sponsor discussions about what the research site will need to meet the study’s enrollment targets.

Upstream from the research site, the sponsor should consider these same aspects when designing the protocol. Engaging participant advisory boards (PABs) can help identify areas in a protocol that may inherently cause barriers to participant identification and enrollment. According to the Tufts Center for the Study of Drug Development (Tufts CSDD), protocols that utilized a PAB recognized a 30% reduction in clinical endpoints, 20% fewer inclusion/exclusion criteria, and a 50% reduction in the amount of data collected. In the context of the DE&I examples discussed earlier, this translates to fewer study visits (mitigating enrollment barriers due to transportation or work schedule conflicts) and fewer stated eligibility criteria, which naturally decreases the number of unstated eligibility criteria.

PABs also provide an avenue for potential participants to voice their concerns and those of the community for which DE&I considerations may not have been given.

Fully understanding “diversity, equity, and inclusion” within clinical research also leads to a deeper understanding of DE&I as its bundled entity. It is easy to identify how the individual components impact each other when one is overlooked.

As DE&I considerations and regulations continue to be brought forth, successful recruitment strategies will need to include pragmatic solutions that mitigate expressed barriers, as well as those that are implied.

Jamie Harper, MHA, CCRP, Vice President, Site Solutions and Engagement, WCG