Introduction

The goal of clinical research is to find ways to prevent, diagnose, and treat disease to improve the overall health and quality of life for all people more effectively. Despite significant investments in clinical research, the differences in health status and health care for many groups in the United States has not been mitigated [1]. With the latest United States (U.S.) census in 2020 [2], the impact of population health challenges will grow exponentially without action.

For nearly 30 years, federal law, National Institutes of Health (NIH) policies, and Food and Drug Administration (FDA) guidance [3,4] have sought to achieve optimized health by emphasizing ethical engagement and representation of all people in clinical research. With less than 15% of clinical trials reporting outcomes by race or ethnicity [5,6] and many investigators still struggling to ensure appropriate representation [7,8], it appears more impactful efforts are needed. In addition, juxtaposing these results is evidence suggesting that despite potential hindrances to research participation such as trust, time, and financial concerns, groups less represented in clinical research indeed “are willing to engage in clinical research” [9–11].

To explore this dissonance of the lack of representation in clinical research, despite the willingness of these groups to participate, we conducted a systematic review to identify evidence-based strategies used to improve recruitment and retention of all groups in clinical research. To our knowledge, this systematic review is among the first designed to qualitatively assess strategies across less represented groups and chronic diseases. Since there is “substantial quantitative data demonstrating the problem of underrepresentation” in clinical research, we sought to achieve a primary objective set forth in Chapter 5 of the recent National Academies of Science, Engineering, and Medicine (NASEM) report entitled Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups [12] and provide evidence-based facilitators of appropriate representation in clinical research. The studies included in our review are primarily from the perspective of individuals across the continuum of clinical research, i.e., participants, caregivers, clinicians, community leaders, and medical center leaders, which complement the NASEM report’s focus on research teams. The results were thematically analyzed to develop a conceptual model from which actionable recommendations emanate. These results align with our unpublished qualitative analysis of NIH-funded clinical studies, for strategies that improved the participation of less represented populations in clinical research. The goal of this review is to provide clinical research teams with strategies that enhance the recruitment and retention of populations in clinical research.

Methods

We adhered to and adapted the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines [13], Enhancing the Quality and Transparency of Health Research (EQUATOR) guidelines [14], and The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to report this completed systematic review and meta-synthesis [15].

Results

Our initial literature review focused on studies that were published between 2009–2020. Subsequent updated searches were performed in 2022 and 2024, to provide a comprehensive update of literature on this topic. Of the total 5,068 studies identified for initial title and abstract screening, 914 studies underwent full text review with 27 studies proceeding to data extraction and quality assessment (Fig 1, [28–53]).

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Fig 1. Flowchart of Study Selection.

Wrong outcome = study does not mention evidence-based strategies; Wrong Study Design = study is not qualitative nor mixed methods design; Wrong patient population = study not focused on race and ethnic groups of interest; Systematic review = study is a systematic review; Not disaggregated by race = unable to determine which outcomes were associated with which race and ethnic group; Wrong indication = not one of the leading causes of mortality and morbidity in the U.S.; Not peer-reviewed, e.g., commentary; Wrong setting = study is not based in U.S.

https://doi.org/10.1371/journal.pone.0322796.g001

S2 Table describes the characteristics of each study included in this meta-synthesis systematic review while Table 1 summarizes the studies in aggregate, separating inclusion criteria from other data extracted during the review. Twenty-five studies implemented recruitment strategies, and two studies implemented both recruitment and retention strategies. Eleven studies focused primarily on Black/African American communities, with four studies involving Latino/Hispanic, two studies involving Asian and one study involving Native Hawaiian/ Other Pacific Islander communities and eleven studies focused on People of Color (POC). No studies focused on American Indian/Alaska Native communities. Nineteen studies (70%) focused on cancer (breast, hematologic, lymphoma, multiple cancers, or not reported), six (22%) focused on Alzheimer’s and dementia, one (3.7%) study focused on kidney disease and one (3.7%) study focused on heart disease. No studies included chronic respiratory diseases, diabetes, pneumonia and influenza, or stroke. Although not used as inclusion criteria for this systematic review, we extracted data related to sex, geography, and with whom the study collected strategies from (sources role in clinical research). Sex was acknowledged in ~40% of the studies, with eleven studies reporting sex of the clinical research participant and/or the person’s role in clinical research. No studies included persons under 18 years old. While nearly 80% of studies reported on geography, no studies solely focused on rural locales. All told, the studies included in this systematic review reflect strategies from individuals whose roles in clinical research were participants, participant networks (i.e., study partner, caregivers), clinicians (i.e., medical staff, healthcare providers, research staff), medical center leadership, recruiters, and community leaders. The characteristics of the study were based on percentages, where two studies included multiple populations [28,42] five studies reported on sex across multiple groups [38,45–47,51]; and seven studies reported multiple roles in clinical research [31,35,38,39,45–47,51]. Studies reporting multiple groups are counted for separately in Table 1.

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Table 1. Summary of included studies for meta-synthesis of evidence-based strategies (N = 27).

https://doi.org/10.1371/journal.pone.0322796.t001

Twelve studies met all quality criteria, while fifteen did not meet all criteria (S2 Table). The most common reason for not meeting all criteria was related to the sampling method and specifically studies not disaggregating strategies by race and ethnic group, i.e., grouping all individuals into POC.

Table 2 describes the deductive codes derived from the direct meaning and content of the studies included in this meta-synthesis systematic review, along with a summary definition, a representative quote, and a listing of the studies reflecting that particular strategy. S3 Table summarizes the frequency the strategies were observed across the included studies, with sub-groupings where appropriate. The most frequently utilized strategies were education (44%), communication (48%), and community-based participatory research (63%). Cultural humility was reflected in nearly 40% of studies. Strategies reflecting relationships (awareness, language, patient navigation, patient-provider relationship, social networks, technology) were evident in nearly one-quarter of studies. And, finally systems, and training were noted in ~20% of studies.

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Table 2. Deductive coding from meta-synthesis of studies on recruitment and retention strategies for groups less represented in clinical research.

https://doi.org/10.1371/journal.pone.0322796.t002

This section summarizes the high-level interpretation and summary of themes derived from the inductive coding. Themes critical for representative clinical research among groups less represented in clinical research included empowerment, sustainability, transparency, and trust. Empowerment explores how education, communication, or other tools seek to empower participants to be involved in clinical research. This includes how participants are empowered to make decisions to engage in clinical research based upon informed decisions, patient navigation, advocating for themselves, and other tools seeking to bolster local capacity through partnerships, collaboration, and community engagement. Within this theme, participants exhibit a sense of empowerment through demonstrating autonomy in making informed decisions about engaging in clinical research. Trust highlights the importance of clinical research staff developing trust with participants or the community. This can include respecting community boundaries, culture, and norms; demonstrating respect through connections, communication, and consistent and repeated contact/positive interactions; using community-based spaces to foster trust for participants; and building trust through enhancing rapport. Transparency demonstrates the need for clear communication about clinical research including benefits and risks, health information, and additional information supporting informed decision-making. Sustainability describes long-term investment into fostering relationships with the community, building sustainable infrastructure such as a systems approach, developing procedures such as databases and registries, and implementing policy approaches to support enhanced engagement among these populations in clinical research.

Fig 2 depicts our conceptual model of recruitment and retention strategies for groups less represented in clinical research, that is an assessment of these aforementioned themes and strategies. This model explores both the strategies reflected in our deductive coding, along with themes derived from our inductive coding. With roles in our meta-synthesis systematic review spanning from research participants to medical center and community leaders, our analysis pointed to the critical need for multi-level approaches. Therefore, our model adapts the socioecological model levels of interpersonal, community, and policy [54]. The interpersonal level demonstrates the themes of trust as well as transparency, with strategies such as communication, patient-provider relationships, awareness, education, and language being most prominent. The community level primarily exhibits the theme of empowerment, with strategies such as patient-navigation and social networks playing primary roles. And, the policy level presents the theme of sustainability, with strategies of a systems approach to reduce research engagement barriers being most pronounced. At the foundation, and essential across all levels, are cultural humility and Community-Based Participatory Research (CBPR).

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Fig 2. Conceptual model of strategies for participation of groups less represented in clinical research.

Interpersonal, community, and policy levels adapted from the socioecological model. Bold text = themes from analysis. Training is embedded primarily within the foundation of Cultural Humility and Interpersonal Level of Trust within Patient-Provider relationships. Technology can be applied at all levels, but its use is evolving rapidly and needs to be considered carefully within the context of Cultural Humility and CBPR.

https://doi.org/10.1371/journal.pone.0322796.g002

Discussion

This is one of the first systematic reviews to qualitatively assess strategies that seek to increase clinical research participation among less represented groups, across the leading causes of morbidity and mortality in the U.S. The initial review encompassed literature from 2009–2020. As the study progressed, additional updates were performed in 2022 and 2024 to include more recent literature. The review includes perspectives spanning the clinical research ecosystem, with emphasis primarily on recruitment, and cancer. Strategies identified along with themes derived from high level interpretation emphasize the need for efforts at multiple levels concentrating on CBPR and cultural humility. This meta-synthesis systematic review: (1) provides qualitative data about evidence-based strategies to recruit and retain groups less represented in clinical research; (2) reveals remaining opportunities and gaps; and (3) details actions for creating a culture of equitable clinical research.

In our review, the strategy that was most frequently used to increase the participation of these populations in clinical research was CBPR; nearly 63% of the studies in our review utilized this strategy (S3 Table). This included direct engagement with the community (58.8%), partnership with community leaders (52.9%), engaging with community-based organizations (17.6%), and receiving feedback from community leaders (17.6%). This highlights the importance of building and maintaining a relationship with the community, from the initiation of study design through the completion of the study. Cultural humility, which was also identified as a strategy, is needed to initiate and maintain a relationship with the community. Cultural humility requires the research team to remove their own assumptions and become the student that respectfully learns how the culture and concerns of potential participants impacts their health behaviors. This approach allows the study team to engage a community, identify potential concerns, design, and implement a study that is culturally sensitive and tailored for those participants. In practice, this may include: (1) providing tailored information, material, and consent forms in the relevant language; (2) using relevant and respectful imagery in study material; or (3) considering practices and beliefs in study design. According to our conceptual model, cultural humility partnered with CBPR is foundational to the recruitment and retention of these populations at the interpersonal, community, and policy level.

Nearly half of the studies in our review noted that clear, consistent communication and education enhanced recruitment and retention of these populations (S3 Table). Effectively communicating and educating participants on study information (i.e., the purpose, disease, study requirements, appointment schedule, risks, benefits, study results) in a manner that is patient, non-condescending, and relatable, was considered an effective technique. Utilizing storytelling techniques to communicate the benefits and risks of the study, was also shown to be an effective strategy. One participant expressed their desire to know more about the study, beyond what is included in the informed consent, emphasizing the utility of clear communication (Table 2). Educating the participant network using programs, flyers, posters, or pamphlets was named as useful strategies. Other strategies that were identified through this review include: (1) supportive patient-provider relationship, (2) use of relevant languages, (3) use of technology like social media and visuals, (4) use of patient navigation, (5) use of social networks, (6) use of systems approach, and (7) training of clinical research staff. While this review focused on studies performed in the U.S., these strategies are applicable to clinical research studies that are performed outside of the U.S., that aim to recruit study participants. There are recommendations and studies from groups outside the U.S. that highlight the use of the strategies identified in this review, for clinical research in countries beyond the U.S. [55,56].

These findings align with our unpublished qualitative analysis, that examined NIH-funded clinical studies to identify strategies that improved recruitment and retention of populations in clinical research. This study surveyed NIH institutes to identify clinical study exemplars that had achieved participation of less represented populations in their study. We collected data from 19 of NIH’s 27 institutes, resulting in the identification of 123 exemplars. Our analysis revealed that the study sites intentionally built and sustained relationships with the community of interest. These sites also had study teams that were representative of the patient population, that contributed to the successful recruitment and retention of these study participants. The exemplar studies collected and monitored the demographic data of study participants. They frequently examined these numbers during the study and adjusted their strategies to ensure that the study enrollment matched the incidence rates of the condition being studied. Lastly, these studies fostered transparency, accountability, and frequent communication between the sponsor and research team as well as between the research team and the study participants. This aligns with the themes identified in our meta-synthesis that are critical for representative clinical research: empowerment, sustainability, transparency, respect, and trust.

This review proceeded concurrently with the recent NASEM report entitled Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups [12]. The scope of the NASEM report extends far beyond our review. However, we have achieved a primary objective set forth in Chapter 5: Facilitators of Successful Inclusion in Clinical Research and provide evidence-based facilitators of appropriate representation in clinical research (Table 2). Our work complements the NASEM report, which focused on research teams, by centering the voices of persons involved across the continuum of clinical research, i.e., participants, caregivers, clinicians, and community leaders (S2 Table).

Our review clarifies opportunities for future scholarship. Previous work has focused on obstacles to participation and how to overcome these challenges in clinical research in general. However, there is a paucity of literature assessing strategies across communities and diseases. Although this review was unable to represent all groups and conditions, this does not imply there is no work being done; rather, the work may be at stages that did not fit the current criteria (e.g., studies identifying obstacles or collecting community feedback about the strategies being tested). The work presented here does highlight the opportunity to assess strategies across populations and diseases as a potential indicator for directly replicating them in a new setting or adapting before implementation. For example, CBPR strengthened by cultural humility [57] were decisively emphasized and, hence, were considered to be foundational (Fig 2). This conclusion is consistent with previous findings related to enhancing engagement of in clinical research [58–61] and is reflected in the recent NASEM report. In centering the community norms, values, voices, and collaborating with the community, CBPR and cultural humility permeate our conceptual model at all levels. One way that cultural humility acts in-service to CBPR is reflected in the evolving landscape of CBPR which recognizes the need for a continuing focus on balancing power in partnerships (e.g., by sharing decision making authority with the community [62]).

There are populations whose perspectives are vital but were not reflected in the studies that are included in this review. Notably absent from the studies included in our review are the perspectives from American Indian/Alaska Native (AI/AN) populations. Qualitative data from AI/AN groups will clarify tailored and adapted strategies unique to these groups. The perspective of young participants (i.e., under the age of 18) was also not represented in the literature included in our review. Given NIH’s Inclusion Across the Lifespan Policy that expanded the inclusion of children in clinical research, having that data would provide guidance on how to design pediatric clinical research studies. Hearing from young persons from less represented groups also has implications for diseases originally considered for this review that are prevalent in youth (e.g., asthma [63]). Also, how each generation relates to the clinical research ecosystem may be unique due to the historical policy, context, and technological advances and therefore will require customized interactions [64]. Finally, the perspective from industry was also absent from the literature in our review. Understanding the perspective of industry is critical, since a vast majority of clinical trials are performed by companies [65].

Lastly, a limitation of our review is that it consisted of studies reporting recruitment strategies but did not include studies with retention strategies. Future work comparing such results is critical when considering Phase 3 clinical trials for drugs and devices typically last 1–4 years [66]. Given the time commitment, size, and cost associated with Phase 3 clinical trials, the theme of sustainability is likely to play a pivotal role in strategies for retention [67–69].

Actions to create representative clinical research proceeded from our thematic analysis and conceptual model. The actions described here should be initiated, rigorously evaluated, and accelerated by establishing and sustaining a community of practice focused on recruitment and retention of less represented groups in clinical research. The community of practice must include representatives from across populations, sectors (government, academia, industry, non-profit, publishing, philanthropic institutions, etc.), and roles in the clinical research ecosystem. The community of practice should be accessible for timely consultation to researchers.

There is a need to engage in thoughtful deliberations about the time, personnel, and funding levels necessary to create a culture of representative clinical research and promote population healthy, via CBPR strengthened by cultural humility. This sentiment was also clearly stated in the NASEM report [12]. From such deliberation, innovative partnership structures spanning sectors may be required (e.g., work analogous to the Framingham Heart Study) [70].

Given the magnitude of health disparities, the future generation of researchers (including undergraduate and graduate students) should receive earlier course curriculum on the importance of representative clinical research. Topics, embedded in science-technology-engineering-mathematics-medicine (STEMM) based pedagogies might include, but are not limited to: 1) acknowledging multi-faceted obstacles to representative clinical research; 2) the facilitators that improve participation of populations in clinical research and how to implement them; 3) understanding how not having representative clinical studies prevents the development of health care innovations [71]; and, 4) understanding that improving clinical research overall could advance but will achieve population health.

It is critical to consolidate and actively disseminate resources about recruitment and retention strategies through recurring educational sessions or creating clinical research offices that provide consultation for researchers. This would allow researchers to promptly replicate and/or adapt strategies for their clinical research ecosystem. To ensure accountability, standards for and reporting of representative clinical research should be considered. Example standards might include, but are not limited to defining appropriate reference numbers for appropriate representation, e.g., population versus disease demographics; intentionally collecting and reporting qualitative feedback on strategies employed; and disaggregating findings by demographic data and role in clinical research ecosystem, etc. To disseminate actionable strategies, partners could develop curricula, hold workshops, and convene summits to share best practices and methods.

Strategies to recruit and retain populations in clinical research must prioritize the needs of the community and operationalize a sustainable multi-level approach where both cultural humility and community-based participatory research are foundational for effective implementation. To create representative clinical research, a re-energized focus needs to include earlier career training to make implementation of strategies intuitive for the next generations of researchers; establishment and monitoring of standards and reporting; and thoughtful deliberation about the time, personnel, and funding levels necessary to advance population health.

Supporting information

Acknowledgments

We would like to extend our sincere gratitude to Mia Rochelle Lowden, Ph.D. and Irene Avila, Ph.D., for their support in planning this study. Their insightful feedback and thoughtful suggestions contributed to the development of this work. We would also like to thank the National Institutes of Health Library, specifically Ms. Alicia Livinski and Ms. Nancy Terry for developing the search strategy and conducting the literature searches.