Access as a barrier

Limited access to healthcare is a major barrier to clinical trial recruitment that disproportionately impacts racial/ethnic minorities [28]. Often, research sites are not located in communities with a high prevalence of racial/ethnic minorities [29]. Thus, participating in research studies may be more difficult due to limited access to affordable and convenient transportation or anxiety from traveling to an unfamiliar location [30]. In our own clinical trial experience, we have seen how limited access to efficient and affordable transportation can make it difficult for participants living at a greater distance to make it to their appointments.

Another factor impeding access to research is the burden disproportionately faced by caregivers from racial/ethnic minority populations. It may be difficult for individuals who care for their family members to take time away from these duties for research visits. Rote et al. found that non-Latino Black, Mexican-origin, and other Latinx individuals were engaged in more frequent and time-intensive elder care compared to non-Latino Whites [31–33]. If these populations are more often the ones needing to care for family members in the home, they may have less time to engage in clinical trials, especially if they have no additional assistance in caretaking duties.

According to the Bureau of Labor Statistics, individuals who identify as Black/African-American or Hispanic/Latinx are the most represented group in service occupations, as well as production, transportation, and material occupations [34]. It is traditionally harder to get paid time off within these occupations, with many employers not offering it at all. During the webinar series, attendees discussed how office hours for clinics and labs that conduct research are typically open during the day, only operating during traditional 9–5 hours, making it difficult or impossible for those in service occupations to attend research visits without taking time off from work. In our studies, we have had many individuals who were interested in participating, but had to decline because they could not afford to take time away from their jobs. This gap can be described as the opportunity cost of research participation. While our literature review did not come across any studies focused on the impact of opportunity costs on racial/ethnic minority groups’ decision to participate in research studies, some studies have shown that minority groups tend to consider opportunity costs more than White populations [35]. Given the lack of current research on opportunity costs and clinical research participation decision-making across racial/ethnic groups, this topic is an important area for future research.

Access solutions

Webinar series attendees discussed solutions to address access-related barriers to study participation, concluding that the inclusion of incentives or compensation as part of the research budget at the institutional level might help to resolve some of these issues. Research institutions and universities should ensure funds are allocated to research studies so that there is always a budget to provide compensation to participants for their time. Paying for or providing childcare, eldercare, and compensating for missed time at work would incentivize many people to participate, as those burdens would be eliminated. Some groups mentioned the importance of making this approach not just institutional, but a national standard for all trials. Additionally, extending clinic hours and having visits outside of traditional office hours would allow individuals who work during the day to participate in trials.

Providing payment for research trial participation is essential to increasing trial diversity because it reduces burdens on individuals in lower socio-economic levels. Minority populations are overrepresented in lower socioeconomic groups, therefore increasing financial remuneration may increase racial/ethnic diversity. Bierer et.al outline the different forms of payment for trials–reimbursement, compensation, and incentives. Patients must be reimbursed for all study-related costs, and compensation for their time and effort in a study is also important. Additionally, budgeting for incentives to participants further increases recruitment of individuals and is a useful strategy for increasing clinical trial diversity [36].

The clinical trialists in the webinar series noted that research-related care should be at no cost to the participant or their insurance. Compensation is provided directly to participants at the time of the research visit to limit the barrier of opportunity cost. Many researchers also suggested providing transportation vouchers to address transportation costs.

Academic medical centers have shifted toward placing research clinics in community-based ambulatory primary care office sites to assist with recruitment, making studies more accessible to potential participants’ neighborhoods. Lastly, some research teams noted success with early morning visits prior to the start of the work-day and evening and weekend research-related activities, thus improving accessibility and retention.

Awareness as a barrier

Awareness is a major barrier to clinical trial participation. Many clinical trial participants find out about clinical trials and research through their physician or doctor’s office. Compared to 7% of White individuals, 23% of Black individuals reported having trouble paying for healthcare services, and racial/ethnic minority populations are less likely to have health insurance [28]. Additionally, racial/ethnic minority groups are more likely to utilize emergency departments for concerns that could be addressed through primary care, and are more likely not to have a primary care provider, meaning many individuals within these minority groups are missing the opportunity to learn about relevant clinical trials available to them [37]. Both of these factors are barriers to the recruitment of racial/ethnic minority groups.

Language is a barrier to clinical trial participation for non-English speaking US populations, which are predominantly racial/ethnic minority groups. In order to communicate and recruit individuals who do not speak English, studies must have interpreters to properly communicate about the study, recruitment, and consent. Materials also need to be translated to the participants’ native language, and not all studies offer this option [38]. Additionally, some studies exclude non-English speakers in their study inclusion/exclusion criteria [39], missing out on potential opportunities for increasing diversity in clinical trials. Even individuals with English as a second language may have challenges in functional health literacy, defined as “the ability to read, understand, and act on health information,” which is a major concern for American patients [40]. Individuals with low health literacy face significant challenges in understanding medical diagnoses, how to take prescription medications, and instructions on how to manage medical conditions. Racial/ethnic minority populations have lower health literacy scores compared to White populations, especially Hispanic/Latinx and Black populations [41], Individuals with lower health literacy are more likely to use emergency health services, and less likely to use preventive primary care services than those with high health literacy, which, as noted previously, is a primary site of clinical trial access and recruitment [42]. For patients utilizing primary care services, primary care providers may need to spend extra time explaining things carefully to patients, leaving little to no time to focus on clinical trial recruitment in visits that are already time constrained.

In addition to health literacy, research literacy may be a barrier to clinical trial diversity. Minority populations may not know how or where to find studies in which to participate, and once they do they may not understand all parts of the process. There are many search engines available to help individuals locate studies that are open for enrollment on the local and national level, such as ResearchMatch (researchmatch.org) or clinicaltrials.gov, but these are not generally well-known. Additionally, once participants have found a research study in which to participate, they may encounter further challenges in understanding the requirements or consent process, which could deter them from participating. One study examined comprehension of consent documents among different racial/ethnic groups [43]. African American, Hispanic, and Asian/Pacific Islander populations had lower comprehension scores than the White group [43]. Understanding what is stated in the consent form for a study is essential for the safety of individuals participating in research, however it also creates another barrier for racial/ethnic minority populations’ inclusion in clinical trials.

Awareness solutions

Many strategies exist to address awareness of research in racial/ethnic minority communities and engage a greater proportion of these populations. In the webinar series, it was noted that recruitment materials must be both relevant and accessible to racial/ethnic minority populations. One study found that presenting culturally-tailored information about studies and disseminating this information consistently and through multiple channels increased recruitment of African American individuals into a cancer screening trial [44]. Utilizing research ambassadors (community members who have participated in research) is another method to increase awareness for minority populations, as non-White patients are more likely to obtain information about research trials from other patients than from physicians or the internet [45]. The Ohio State University Center for Clinical and Translational Sciences and other academic institutions have developed the “Community Scientist Academy”–a 6-week boot camp to increase community members’ and stakeholders’ awareness and understanding of research and to increase engagement throughout the entire translational research process. Participants from this program are equipped to go out into their communities and be ambassadors for clinical trial participation [46].

Increasing knowledge of research trials in racial/ethnic minority populations requires research staff to engage with the communities of interest. Community-based participatory research (CBPR) is an effective strategy for recruiting minority populations because it empowers communities to become involved in the entire research process [47]. CBPR gets community stakeholders involved from the start, thus allowing the research team to co-develop recruitment strategies tailored to the community of focus [47]. CBPR, community-engagement, and academic-community-government partnerships are key solutions in the armamentarium to increase clinical trial diversity, but take intentional efforts from invested institutions, researchers, and communities [1, 23, 24, 47].

Racism in research

Racism in its many forms is a critical factor inhibiting clinical trial diversity. There are various complex issues surrounding perceived, interpersonal, institutional, and structural racism that serve as major obstacles to recruitment of minority groups in research (Table 5).

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Table 5. Definitions for types of racism [83].

https://doi.org/10.1371/journal.pone.0281940.t005

A major barrier to recruiting minorities to clinical research trials is lack of trust [24]. This issue is one of the most studied barriers to diverse clinical trial participation, as it is arguably the most significant [48]. Mistrust in the medical and scientific communities is directly linked to the issue of anti-racial/ethnic minority group racism [49]. All forms of racism, including structural racism, have devastating health consequences and are at the root of many of the US health disparities, whether directly linked to medical outcomes or by creating medical mistrust [49].

There is an extensive history of racial/ethnic minority groups being abused, exploited, and endangered in the medical field and beyond. One of the most commonly cited examples is the Tuskegee Syphilis Study on African American Men [50]. This may be one of the most well-known instances, but there are many others that further solidify the mistrust minority populations have in the medical field–The Havasupai diabetes project in the Native American population [51], the forced sterilization of Native American women [52], Latinx women [53], and inmates [54] and the sexually transmitted disease experiments in Guatemala [55]. Many of these instances, among others, have been well documented in Medical Apartheid by Harriet A. Washington [56]. These events have led to a combination of mistrust and fear of healthcare personnel and the healthcare system. Minority groups may feel that by participating in a clinical trial, they will be unethically experimented on for new medical interventions [28, 57]. The clinical trial investigators on the webinars noted much greater resistance for studies involving medications vs. non-medication intervention, particularly if the medication was for prevention. Investigators noted participants were concerned about why they were being chosen for trials when contacted by research teams and specifically questioning why they were being recruited. The history of mistreatment faced by racial/ethnic minority groups may lead some to assume the worst when being approached about research.

While historical events play a significant role in increasing mistrust of the healthcare field in Black populations, there is also the issue of present-day discrimination and racism in healthcare [38, 58, 59]. This racism can be manifested as overt, interpersonal racism in interactions with healthcare staff [58, 59]. Additionally, there is extensive evidence that racial/ethnic minority populations in general and especially Black populations have worse health outcomes due in part to receiving lower quality of care [60]. The combination of historical and present-day racism and unethical abuses in research is a major barrier to gaining trust and clinical trial recruitment.

Solutions to racism in research

An effective strategy for gaining the trust of racial/ethnic minority populations as a researcher is to engage with the community and understand their needs so that research studies address the needs and values of the community [1, 24]. Oftentimes, racial/ethnic minority groups feel more motivated and willing to participate in a study if they believe it will directly benefit them or their friends and relatives [61]. Some investigators on the webinars noted they engage with each participant individually and explain their values and personal connection to the community and the study. Investigators also emphasized the history and purpose of specific medications (Table 6). As an additional layer of safety for participants, the principal investigators noted how they monitor each participant closely for adverse reactions, even more so than would be done outside of a research setting to further ease participants’ concerns. Participants have responded well to these efforts, and community members on the webinars felt these were helpful techniques, as they noted the importance of communication that is culturally appropriate.

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Table 6. Barriers and solutions to clinical trial diversity.

https://doi.org/10.1371/journal.pone.0281940.t006

Another strategy for addressing mistrust in minority populations is education [62]. Working with trusted community leaders and organizations to educate populations will increase the level of trust in the community. Additionally, disseminating and sharing study results directly with the communities that participated in the research and are impacted by the conditions the research is addressing will increase their engagement with the research field and make them feel like a valued part of the research process, which will also increase trust [63].

Furthermore, work discussing racism needs to be published. Some studies examine disparities between racial and ethnic minority groups in response to medications or treatments, but more needs to be done specifically to address racism in all forms from the socio-political lens, particularly within healthcare and in the communities healthcare organizations serve. Leading medical journals and organizations have recently begun to focus on the health effects and negative consequences of structural racism [64, 65]. The medical and research community must aggressively address racism if we wish to gain trust from marginalized groups.

While creating a trusting environment and relationship with racial/ethnic minority groups and the research workforce is essential, blaming low participation on racial/ethnic minority groups themselves is incorrect and must be curtailed. Framing the discussion of solutions must focus on eliminating the causes of mistrust and addressing the systemic racism that racial/ethnic minority populations face in order to gain trust [66]. As stated by Boyd et al., race should be used intentionally and for the right reasons when designing research studies. Not only should race and the reason for its inclusion be specifically identified and defined, but studies examining race should also include discussions on how racism affects health outcomes [66]. Dr. Boyd’s comments also speak to the need to measure racism in healthcare, and researchers and investigators in the webinar shared tools and strategies for measurement [59].

Webinar series attendees focused heavily on tackling issues of racism to increase clinical trial diversity in the dialogue with presenters and in the breakout room discussions. Many novel insights were garnered from those discussions. First, increasing researchers’ awareness of some minority groups being sensitive to the fear of identification due to undocumented status is key [67]. Attendees also discussed the importance of education, but specifically in educating the workforce on historical trauma faced by racial/ethnic minority populations so that they can engage from a place of understanding and humility. Attendees also discussed the idea of putting specific enrollment targets in place for White vs. non-White participants based on disease prevalence in the population, to promote targeted clinical trial diversity relevant to the phenotype of the disease.

Clinical trial and primary care provider workforce diversity

The lack of diversity in the clinical trial workforce is another major barrier to increasing minority participation [68, 69]. Specifically, the lack of diversity in clinical research coordinators is a significant hurdle to performing high-quality, generalizable research for underrepresented racial/ethnic minority groups in medicine and science [20]. Clinical research coordinators are a key pillar in the successful recruitment and retention of participants in clinical trials, and diversification of the clinical research coordinator workforce has been a cornerstone of recent recommendations on solutions to diversify clinical trials [5, 70]. The investigator and clinical research coordinator are both vital to implementing inclusive trials, as coordinators are the face of the trial from the participants’ perspectives and principal investigators are typically the lead of the whole operation [5]. Cultural competence and humility by the principal investigator, coordinators, and site staff are essential for increasing clinical trial participation [5].

Studies show that racial concordance plays an important role in racial/ethnic minority groups’ decision to participate in clinical trials [69]. Therefore, having fewer investigators and research staff who are racial/ethnic minorities likely leads to less recruitment of minorities into trials [71, 72]. Racial concordance is helpful in racial/ethnic minority recruitment, but it is only the start of the researcher-participant relationship. Research staff must also have concordance in the aspects of language, culture, and goals for the community to truly engage and recruit racial/ethnic minority groups into clinical trials [62, 68]. Miscommunication causes misunderstandings of the details of a trial and can lead to hesitancy about participation, which is why it is important that researchers can understand the cultural and language barriers some populations may have [28]. Cultural beliefs on the part of the research staff are also important because it influences whom they seek for participation. Some providers and researchers believe that racial/ethnic minority groups are not interested in clinical trials, therefore they do not recruit them for their studies [62].

Another strategy for enhancing concordance and communication with racial/ethnic minorities in the literature includes establishing collaborations with primary care providers in the communities of interest [63]. Working through providers who have established trust with their current patients can lead to better understanding of the trial and benefits to potential participants. Another issue investigators have seen in study recruitment is patients being recruited based on a study qualifying condition who were not aware of their condition at the time of contact. This situation is why working with primary care providers is critical to not only obtaining permission to recruit patients, but to also ensuring patients are seeing their physicians and are aware of all their health issues.

All of these solutions may be effective in promoting diversity in clinical trial research participants, but are mere Band-Aids on the fundamental issue of a lack of diversity in the clinical research workforce. Minority researchers and scientists are more likely to recruit minority populations into their studies, but they make up a small portion of the research workforce [73]. Furthermore, the research topics proposed by racial and ethnic minority workforce populations are less likely to receive funding, yet another factor decreasing diversity in the clinical trial workforce and ultimately clinical trials [74]. Funding organizations must promote diverse researchers and research projects that focus on diverse communities in order to increase racial/ethnic minority participation in clinical trials. Luckily, these organizations are moving in the right direction, with the National Institutes of Health (NIH) creating grants and programs to increase funding for health disparity and community-based research. Additionally, programs like the Endocrine Society’s Future Leaders Advancing Research in Endocrinology (FLARE) program supports underrepresented individuals pursuing research and science by promoting their careers in endocrinology-related research [75]. Projects that create solutions to increasing the diversity of the research workforce will lead to an increase in the diversity of the participants as well.

Strengths and limitations

There are many strengths to be highlighted with this work. The webinars were inclusive of multiple perspectives from individuals in academia, community members, clinician researchers, biotechnology and biopharmaceutical representatives, and employees or representatives of government organizations. By bringing together so many different groups, we were able to gain a rich diversity of perspectives. We also had a large number of participants across the two webinars, expanding the breadth of perspectives we were able to reach. Lastly, the development of all the topics and themes for the webinars were conducted with community member input to ensure we covered topics that were relevant to those we wish to serve.

Even with these strengths, our work must be considered in light of some limitations. First, a majority of the participants came from Ohio due to the seminars being hosted by an Ohio university and therefore generating the most interest from the surrounding area. Additionally, the webinars were held at noon during the weekday, which likely prevented some people who may have had interest from participating due to work-related commitments. By nature, group sessions may not allow for deep exploration of a topic from the viewpoint of one individual like an interview, and some people may not have shared sensitive information in the communal session; however, group discussions allowed us to obtain many perspectives in the webinar session. Lastly, we collected limited sociodemographic information from attendees, which we plan to enhance in future work.

Conclusion

Clinical research has advanced medical treatments and interventions significantly over the past 50 years, but racial/ethnic minority groups are not receiving the same benefits as non-Hispanic White populations, and continue to experience disparities in chronic diseases and life expectancy [76]. Despite 41% of the U.S. population consisting of racial/ethnic minority individuals, this diversity is not represented in the clinical trial participant population [77]. This is a major issue for health and healthcare equity. Racial/ethnic minority groups are not to blame for this inequity. Rather, the cause is a lack of effective recruitment strategies addressing the significant barriers to clinical trial diversity. An intentional focus on solutions to the major barriers of access, awareness, discrimination and racism, and workforce diversity will improve recruitment and retention of racial/ethnic minorities in clinical trials and eventually lead to better health for the US as a whole. Hope is on the horizon as these disparities have been improving [3]; and COVID-19 clinical trials were more representative of the US population compared to prior studies [78, 79]. More funding organizations, like the NIH, are becoming intentional about promoting inclusive excellence [73, 80]; for instance, their large scale All of Us Research Program has paid particular attention to ensuring diversity from historically underrepresented groups [81], and the Food and Drug Administration provided guidance to the industry on enhancing clinical trial diversity [82]. Addressing the barriers and implementing the solutions identified through the “Health Equity through Diversity Webinar Series” and in the current literature are critical to sustainably advancing clinical trial diversity.