Case for the Underdog: Unleashing the Potential for Small, Community-Based Research Sites

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The push for greater racial diversity in clinical trials is essential and widely acknowledged across the industry as most recently evidenced by the FDA’s Diversity Action Plan to improve enrollment of historically underrepresented populations.¹ This effort hinges on the capabilities and reach of clinical research sites and the frontline workers who do the important work of engaging, enrolling, and interacting with participants. In this article, we focus on small, independent community-based research sites (CBRS) that can offer a world of potential for sponsor companies, especially when it comes to reaching and engaging marginalized racial minority communities. Many of these sites are typically located in racial minority communities and are often, operated and/or owned by members from those communities, giving them an edge related to understanding their patient community, such as knowing what community events and fairs to attend and having insights into the unique health needs and challenges faced by members in their communities. Community members are also more likely to trust the staff members who mirror the patient community served, which can facilitate study engagement and recruitment efforts down the line as trust plays an important role in shaping people’s willingness to participate in clinical trials.²

Despite their potential for impact, many CBRS research sites are faced with an uphill battle when trying to secure studies from sponsor organizations and contract research organizations (CROs). For example, CBRS have to compete with larger integrated research sites where most clinical trial studies are conducted.³ This is primarily driven by the fact that sponsors prefer to work with primary investigators who are key opinion leaders (KOL) in their respective therapeutic areas, making it difficult for smaller sites and their principal investigators to “break through” and establish an “in” with the sponsor. In fact, existing research suggests that a sizable portion of studies are conducted at university-affiliated hospitals/large academic research centers, correlating with the tendency for sponsors to work primarily with research scientists affiliated with academic institutions.^4,5 Consequently, small research sites are less likely to be considered for clinical trial studies, particularly in therapeutic areas dominated by KOLs.

A recent survey that was conducted among 10 CBRS located in the US supports this trend. See Table 1 for a description of the participating sites. According to the survey results, most sites, 46.6%, relied on word-of-mouth-referral to secure studies, followed by brokers such as Elias Research Associates (40%) and site networks such as WCG (26.7%), CROs (24.6%), and clinicaltrials.gov (12.75%). About 10.5% of respondents shared that they obtained studies directly from sponsors.

Table 1. Description of community-based research sites surveyed

Source: Tufts CSDD

CBRS are also faced with challenges related to access to study equipment. Owing to their relatively smaller size, these sites may not have study specific equipment that might be more readily accessible for larger institutions, such as MRI and CT machines. To illustrate, the survey revealed that although most sites had basic equipment, such as drug storage rooms; lab rooms; monitoring rooms; as well as equipment, such as a minus 80°F freezer to store biological samples and ambient centrifuges, 50% reported having access to an ultrasound or refrigerated centrifuge, and none reported having an MRI or CT machine (only one site had an X-ray system).*

Another challenge faced by CBRS is that they typically run smaller volume of studies, which may deter sponsors—particularly, mid to large sponsors that have a larger portfolio—from partnering with smaller sites. For example, among the 10 sites, the average number of study volume based on number of active, ongoing trials, was 7.6, which is less than the number of studies conducted at larger research sites, which is typically more than 11 studies.⁴ Sponsor companies may choose to continue working with larger sites that can handle a larger volume of studies.

However, this paradigm of conducting research could benefit from a reframe and deserves to be re-examined particularly as it relates to the racial gap in clinical trial studies. Patient recruitment is cited as one of the primary challenges across different therapeutic areas in clinical trial studies, and this is especially true when it comes to recruiting and enrolling racial minority patients.⁶ Many research sites in the US are located in relatively affluent areas where the patient population is less likely to be racially diverse, and therefore lack the proximity advantage that small research sites located in less affluent and more rural communities may have.⁴

Given these challenges, both sponsors and sites must build synergies to maximize outreach efforts into marginalized communities. We first outline steps that sponsors can take to invest in community infrastructure, training, and partnerships.

Invest in building relationships with small sites

Sponsors can look for opportunities to go beyond their existing network of sites to build direct relationships with CBRS. Many sponsors prefer to use clinical research sites with whom the sponsors have done previous studies, which tend to be larger sites, such as academic institutions or large network of sites. Indeed, it is estimated that community-based sites make up less than 10% of the clinical research landscape, which is dominated by large academic, dedicated, or clinical care integrated sites.⁷ However, according to a recent study examining site activation and patient enrollment outcomes, small sites enrolled 197% of patients expected on average, a rate that is significantly higher than other site types.⁷ This statistic coupled with the fact that many CBSR are located in underserved communities highlights the potential that they can offer to help sponsors diversify their studies.

Relatedly, engagement efforts could also benefit from transparency in the form of follow-up communication that includes feedback about why a site was not chosen after the initial study initiation conversations between the sponsor and site(s). Approximately, 63% of survey respondents shared that they do not receive feedback regarding why their site was not chosen, creating an information gap between sponsors and sites and hampering the efforts of CBRS to improve (see Table 2). To remedy these gaps, we encourage the exchange of timely follow-up and constructive feedback that can not only help CBRS improve but also build rapport and trust with sponsors. In sum, by making a concerted effort to engage directly and build relationships and trust with smaller CBRS, sponsors can be better equipped to expand and diversify their reach, especially among underserved communities served by these CBRS.

Table 2. Characterizing follow-up interactions between sponsors and sites

Source: Tufts CSDD

Embrace decentralized recruitment strategies

Typically, many sponsors use a centralized recruitment method, which we define as a recruitment model where a single, central entity—usually an external vendor—manages the entire recruitment process for a given study. This contrasts with a decentralized recruitment approach where multiple entities that include sponsors, sites, and physicians simultaneously contribute to the recruitment for a given study. Though a centralized recruitment strategy can offer benefits by providing a streamlined experience for the sponsor, decentralized efforts can be more nimble, efficient, and customizable, especially when implemented by CBRS located within the target communities. Given their location within the communities, CBRS staff are more likely to know their local patient population and understand, for example, where potential participants might congregate during community-gatherings or what social media platforms different groups within their community use, which can inform the type of strategy the site can use to reach the study population. The staff are also more likely to know the local language preferences and be able to accommodate participants in the language of their choice. When recruitment is overseen by a local organization within the community containing the target population, the recruitment team is better able to not only track the progress of different recruitment methods, but also respond and adapt the recruitment methods, if necessary, ultimately maximizing recruitment outcomes and reducing cost.⁸ We argue for dedicating more resources to community-based recruitment efforts that can help maximize recruitment outcomes.

Demonstrate the effectiveness of recruitment strategies

An efficient recruitment method can spur interest, generate leads, and ultimately enhance study enrollment outcomes, an area where CBRS has potential to thrive, especially when given the resources and agency to do so within their own communities. For example, according to the survey, the most common methods used to recruit patients were through primary healthcare providers who worked in healthcare clinics in the community (beyond the primary site) and through electronic health records (see Table 3). These outlets could provide sponsors with access to racial minority patients that they otherwise would not be able to reach.

Table 3. Distribution of recruitment methods used by CBRS

Source: Tufts CSDD

Quantifying the impact of centralized and de-centralized recruitment methods across different therapy areas can help sponsors determine the utility of the different strategies, particularly for recruiting racial minority participants. Given that CBRS can leverage their relationships with community-based physicians and have access to racial minority patients in their databases and/or communities, they may be better able to demonstrate a higher study enrollment impact than sites that are not based in those communities. Gathering and benchmarking recruitment data on studies that use community-based and/or centralized efforts can provide decision-makers information regarding the appropriateness of using a centralized or a de-centralized approach; highlight the effectiveness of recruitment methods based on therapy area; and inform more accurate cost allocations. Ultimately, quantifying the impact of recruitment methods can help demonstrate the effectiveness of tailored approaches that can be implemented by CBRS to recruit and enroll racial minority patients.

Invest in community outreach initiatives

Members within most racial minority groups rely on others within their community to learn about clinical research. This is because Black, Latino/a, and Asian patients are less likely to be informed of clinical trials by their healthcare providers than White patients.⁹ Thus, racial minority patients must depend on other ways to learn about clinical trials, with many relying on members within their communities for such information. This is why community engagement efforts become even more critical when trying to reach racial minority communities. Community engagement through partnerships with local organizations, such as places of worship, health fairs, and community centers is one method that can help build trust and awareness of medical research among communities, including Black, Latino/a, and Asian populations who are more likely to trust tailored information coming from members within their communities.^10–12 What’s more, these efforts must be sustainable and ongoing. Building rapport and trust with the patient communities through patient engagement takes time, resources, and effort. However, as illustrated in Figure 1, doing so in a consistent manner can build patient’s trust and likability towards sponsors and sites, increase their knowledge of clinical trials, and motivate them to learn more about clinical studies, such that when a study is ready to launch, the trust and rapport have already been established, increasing the odds that the study will meet its recruitment and enrollment metrics.

Figure 1. Model illustrating downstream impact of patient engagement on recruitment mediated by patient-centered outcomes

Source: Tufts CSDD

We have so far delineated ways sponsors can partner with CBRS to conduct community-based recruitment. Next, we outline strategies that CBRS can employ to attract the attention from study sponsors, which is often one of the major hurdles that these sites must overcome.

Demonstrate quality and reliability

Sponsors view sites as either assets or liabilities based on their performance. To be considered an asset, sites can consistently demonstrate high-quality data, robust recruitment, and strong retention rates. This involves meticulous attention to the details of clinical trial operations and delivering on promises made to sponsors. Clear, measurable results in these areas can significantly boost a site's reputation, making it more attractive for future studies. Sponsors are more inclined to continue partnerships with sites that have a proven track record of reliability and success.

Focus on brand building and community integration

Beyond immediate recruitment efforts, sites can invest in building a strong, recognizable brand within their communities. This involves consistent, positive engagement through various media channels and community events. Establishing a reputation as a site that is deeply integrated into the community can enhance trust and interest from potential study participants. Engaging with local influencers and micro-influencers can further amplify this effect. For example, featuring popular local figures on a site’s podcast or social media can extend the site's reach and foster a sense of community involvement.

Invest in community outreach initiatives

Community outreach is critical for demonstrating a site's commitment to diversity and participant recruitment. It’s recommended that CBRS also invest in their community through outreach and education efforts to share information about clinical research and gain the trust of the patients in their community long before a study launches. As outlined in Figure 1, patient engagement efforts must occur before sites can recruit. While budget constraints are a common concern, sites can approach sponsors with well-defined, cost-effective outreach plans that are built into the start-up costs. Sponsors are more likely to invest if they see that their funds will be used effectively and transparently. For instance, requesting smaller, standardized amounts for outreach can help build trust. By genuinely engaging with local communities, such as raising awareness among Native American tribes or other underserved populations, sites can prove their value to sponsors. Even a small success, like a few randomizations or screen failures, can be significant in showing a sponsor the site's potential.

Build strong community relationships through digital media

Similar to what we delineated for sponsors, sites can also build a strong presence in the local community through digital media and local partnerships. Hosting podcasts or interviews with local business owners, such as restaurant or coffee shop owners, can create a positive brand image and establish the site as a community-centric organization. These business owners often have their own customer base, who could become potential clinical trial participants. This strategy not only builds goodwill but also positions the site as an integral part of the community network, fostering long-term relationships that can benefit recruitment efforts.

Conclusion

CBRS have the potential to shift the clinical trial landscape towards studies that are more accessible, diverse, and representative of the racially and ethnically diverse US population, improving our understanding of precision medicine. However, much work needs to be done by both sponsors and sites to unleash the unique potential that small, community-based sites can offer. By making a concerted effort to reach out and partner with one another, both sponsors and sites can create synergies aimed at breaking down barriers to encourage more racial minorities to participate in clinical trials. CBRS are starting to shape the clinical trial landscape in collaboration with sponsors, which in turn may increase enrollment, allowing for quality and reliable data being collected. Sponsors and CROs can contribute to this effort by shifting their efforts to focus on more CBRS collaborations.

*Sites that did not have imaging machines, such as MRI, CT Scan, or Dexa Scans in their immediate facility shared that they had access to these equipment via local vendors.

Jennifer Kim, PhD, research assistant professor, Tufts Center for the Study of Drug Development, Tufts University School of Medicine; Elaine Palmer, director of clinical operations, Pivotal Research Solutions; Judy Galindo, executive director, Sun Valley Research Center, Inc; and Dan Sfera, president, Yuma Clinical Trials

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