The Importance of Including Underserved Populations in Research

Abstract

This paper provides an overview of the ethical considerations surrounding the exclusion of underserved populations in later-phase clinical trials. Underserved populations, defined here as those with restricted access to or limited benefits from healthcare, often face systemic, logistical, and social barriers that limit their participation in research. This lack of representation not only undermines fairness in research but also hampers the development of effective, inclusive healthcare practices. This paper argues that including underserved populations in research is crucial for promoting justice, increasing the generalizability of research findings, and building trust in medical institutions. It differentiates underserved populations from other populations of interest, including vulnerable, minority, and underrepresented groups and highlights the unique challenges each group faces. It then explores barriers and targeted solutions for four populations: rural residents, racial and ethnic minorities, low-income individuals, and older adults. Strategies for improving participation include expanding trial sites to accessible locations, addressing financial and logistical barriers, broadening eligibility criteria, and fostering culturally tailored outreach and engagement. While some interventions may apply across groups, effective solutions will require intersectional and context-specific strategies tailored to each population’s unique needs and coordinated efforts from multiple stakeholders. While these interventions alone cannot resolve healthcare inequities—since underrepresentation in research is just one contributing factor—their widespread implementation would represent meaningful steps toward advancing health equity.

1. Introduction

If clinical research is to succeed in answering clinically relevant questions, informing care decisions, and improving patient outcomes, it must include all those populations we wish to benefit. This, in turn, requires that underserved populations are enrolled in research. Here, we understand “underserved populations” to mean those that experience greater barriers to accessing health care, have more limited access to health care services, and/or receive fewer benefits from health care compared to the general population [1].

Various populations in the United States—including underserved populations—are consistently underrepresented in clinical trials, raising profound concerns about justice, fairness, and trust. This lack of representation not only reinforces existing healthcare inequities, it also weakens the generalizability of research findings, limiting their applicability to diverse patient populations. Without inclusive research, critical data on how health interventions impact underrepresented groups remain absent, resulting in healthcare solutions that are less effective, particularly for populations already experiencing barriers to care. This is an ethical issue as well as a scientific one.

This article addresses the ethical dimensions of engaging underserved populations in later-phase clinical trials. While it focuses on clinical trials, many of the barriers and solutions we discuss apply to research more broadly. The article proceeds in three parts. First, we define underserved populations and distinguish them from related groups. Then, we argue that including underserved populations in research is crucial for promoting justice, enhancing the generalizability of findings, and fostering trust, all of which contribute to a more equitable healthcare system. The third section details the barriers to clinical trial participation for four underserved groups—rural, racial and ethnic minority, low-income, and older adult populations—and proposes targeted solutions to illustrate the kinds of tailored interventions needed to promote inclusion.

2. Who is “Underserved”?

The term “underserved” is often used alongside “vulnerable,” “minority,” or “underrepresented.” These terms, while conceptually related, are not interchangeable.

We understand underserved populations to be those that experience greater barriers to accessing health care, have more limited access to health care services, and/or receive fewer benefits from health care compared to the general population [1]. This designation reflects a group’s relationship with the health care delivery system. These disparities arise from a combination of patient-specific factors, social-support dynamics, healthcare provider and organizational influences, as well as broader policy and community factors [2]. Examples of underserved populations “include low-income families, rural populations, people with disabilities, refugees and immigrants, and members of the LBGTQ+ community” [3].

Underserved status is defined by systemic barriers—such as provider shortages, geographic isolation, and financial constraints—that limit access to healthcare. While underserved populations often overlap with minority, vulnerable, or underrepresented groups, these terms are not interchangeable. The ways in which underserved populations experience barriers to healthcare do not always align with the factors that contribute to research underrepresentation, vulnerability, or minority status. The specific ways these categories overlap—and remain distinct—are discussed in detail below.

Vulnerable populations, as used here, are those that require additional or special protections when participating in research. Although there is general agreement that some groups need such protections, there is no consensus on how to define vulnerability [4]. Research ethics guidelines and regulations, therefore, typically provide examples of vulnerable populations. These include children, pregnant women, fetuses, prisoners and other institutionalized individuals, and those lacking decisional capacity [5, 6].

As might be inferred from these examples, vulnerability is often understood to be consent-based. Children and individuals with impaired decision-making capacity may be unable to comprehend or appreciate key information about research participation, undermining the ethical requirement that consent be informed. Meanwhile, prisoners and other institutionalized individuals may be more prone to coercion or undue influence, which could compromise the voluntariness of consent [7]. Vulnerability might also be understood as harm-based. Pregnant women or fetuses, for instance, are often thought to be at greater risk of being harmed in research. Seeking a more comprehensive definition of vulnerability, Samia Hurst proposes “that vulnerability as a claim to special protection should be understood as an identifiably increased likelihood of incurring additional or greater wrong” (emphasis in original) [7]. This definition is broader than either consent- or harm-based definitions, as it can encompass both. For our purposes, we will draw on Hurst’s definition and say that vulnerable populations require more protections than those already afforded to research participants generally because of their increased likelihood of being wronged.

Minority populations are subgroups of the larger population (not limited to health care or research contexts) defined by unique characteristics – such as race, ethnicity, religion, culture, or disability status. While ‘minority’ may simply signify that one group is numerically smaller than another, ‘minority’ (or some have suggested ‘minoritized’) is frequently used to imply that a group has been singled out for differential treatment [8]. Minorities often experience healthcare disparities that contribute to poorer health outcomes; this is driven by factors such as provider bias, systemic racism, and inequities in the social determinants of health.

Membership in a minority group does not necessarily make an individual a vulnerable research participant. To offer one example, there is no prima facie reason to think that racial or ethnic minorities as a group are less able than others to give voluntary informed consent for research participation. Still, minority groups may experience vulnerability [9]. For instance, people with disabilities are the single largest minority group in the United States, and within that broader group, those with cognitive disabilities may have impaired decision-making capacity (discussed above as a source of vulnerability). It is also essential to acknowledge the egregious history of research abuses perpetrated against minority populations in the United States. Abuses against racial and ethnic minorities include (but are hardly limited to) the U.S. Public Health Service’s unethical Tuskegee Study of Untreated Syphilis in the Negro Male (“Tuskegee Syphilis Study”) [10].

Finally, we turn to populations underrepresented in research. Underrepresented populations are those whose members participate in lower numbers than their proportion in the general population would suggest [11]. This underrepresentation can be identified through comparisons of research samples to general census data or by recognizing that certain conditions have a higher prevalence among specific subpopulations that is not reflected amongst research participants. The “underrepresentation of racial groups, ethnic groups, and females” has been a longstanding concern in research [12], as has underrepresentation of children, older adults, rural residents, LGBTQIA+ individuals, and disabled individuals [13].

While there is substantial overlap between vulnerable, minority, and underrepresented populations in research, the factors contributing to their underrepresentation are often interconnected rather than entirely distinct. For vulnerable populations, a protectionist approach—intended to safeguard their wellbeing—can inadvertently lead to their exclusion from research. At the same time, structural barriers, institutional bias, and lack of trust disproportionately impact minority populations, limiting their participation in research [11, 14]. Importantly, some groups—such as prisoners—may be classified as vulnerable minorities, illustrating how mechanisms of exclusion frequently overlap. Addressing over-protectionism for vulnerable groups may also have the indirect effect of increasing participation among some minority populations, as efforts to recalibrate regulatory safeguards can help to mitigate exclusionary practices [15]. Understanding these overlapping yet varied causes of groups’ underrepresentation is important for developing targeted strategies to enhance their research participation.

Being underserved in healthcare and underrepresented in research are mutually reinforcing conditions. On the one hand, limited healthcare access reduces opportunities for research participation, as fewer interactions with healthcare providers mean fewer chances to learn about or be recruited for studies. Additionally, restrictive eligibility criteria used in research to control for confounding variables often result in the exclusion of participants with comorbidities, disproportionately affecting underserved populations [16]. On the other hand, research underrepresentation can reinforce healthcare disparities—when studies fail to include a representative sample, the resulting treatments and medical interventions may be less effective or less accessible. In some cases, the same systemic barriers that limit access to healthcare—such as geographic isolation in rural areas—also restrict research participation, further perpetuating cycles of exclusion [17].

Although underserved populations often overlap with minority, vulnerable, and underrepresented groups, they are not synonymous. As Table 1 illustrates, an individual may be underserved without necessarily belonging to these other categories, and vice versa. Because individuals often hold multiple identities at once, examining how these intersecting factors shape access to healthcare and research participation helps inform more equitable practices. Intersectionality provides a valuable framework for capturing this complexity, offering insights into how overlapping social identities—such as race, sex, gender, disability status, and social class—intersect to influence experiences of privilege or disadvantage in both healthcare and research settings [18].

Table 1:

Illustrating the intersectionality of different group memberships for underserved, minority, underrepresented, and vulnerable populations through two vignettes. These examples highlight how individuals with intersecting identities, such as race, socioeconomic status, geographic location, and health conditions, may belong to multiple groups facing barriers in healthcare and clinical research. This complexity underscores the need for tailored research and healthcare approaches to ensure equity and inclusivity.

Examples	Group Memberships
A Black woman with metastatic breast cancer	Is she a member of a vulnerable population? No. On the basis of the information provided, there is no reason to think she is vulnerable. Is she a member of a minority population? Yes. Black individuals comprise the second largest racial or ethnic minority population in the United States [83]. Women are often considered a minority group because they do not share in the same privileges as men. Minority women often experience particular disadvantage. Is she a member of a population underrepresented in research? Yes. Black patients and women are consistently underrepresented in oncology clinical trials [84]. Is she a member of an underserved population? Yes. Historically, Black women have had lower rates of screening mammography, leading to “a higher proportion of late-stage diagnoses and lower survival rates” [85].
A White man with both Down syndrome and Alzheimer’s disease living in a rural community	Is he part of a vulnerable population? Likely. Both Down syndrome and Alzheimer’s disease affect cognition [86]. Though cognition is not the same as capacity, cognitive impairment is often associated with impaired decisional capacity. A capacity assessment would be necessary. If this man is found to have impaired capacity, he falls into a recognized vulnerable population. Is he part of a minority population? Yes. The White population remains the largest race or ethnicity group in the United States [87]. People with disabilities are the “single largest minority group in the country” [88]. About a fifth of the U.S. population lives in rural areas [89]. Is he a member of a population underrepresented in research? Yes. The White population is overrepresented in Alzheimer’s disease research [90]. Nevertheless, this man is part of an underrepresented group. Individuals with Down syndrome “have a lifetime risk for dementia in excess of 90%,” but are generally excluded from Alzheimer’s trials [91]. Further, rural populations are underrepresented in research [39]. Is he part of an underserved population? Yes. Alzheimer’s disease “has a unique impact on … underserved populations including people with intellectual and developmental disabilities (IDD)” like Down syndrome. Symptoms of Alzheimer’s may be different for those with IDD, contributing “to missed diagnoses and delayed interventions resulting in poorer quality of life” [92]. Further, in many rural areas, there is a lack of specialists, and long travel distances may create access barriers to specialized care [93].
Rural, white, middle-class man	Is he a member of a vulnerable population? No. There is no inherent reason to assume vulnerability based on the information provided. However, certain structural and health disparities disproportionately affect rural populations, particularly in access to specialized medical care, emergency services, and clinical trials [44, 94]. If additional factors—such as disability, chronic illness, or economic instability—were present, they could contribute to vulnerability. Is he a member of a minority population? No. If he is white and non-Hispanic, he is part of the racial/ethnic majority in the United States. Is he a member of a population underrepresented in research? As a rural resident, yes. While the white population is generally overrepresented in research, rural populations face significant barriers to participation and are underrepresented in clinical trials, public health studies, and dementia research [94, 95]. Structural barriers such as geographic isolation, provider referral gaps, and lack of research infrastructure contribute to this underrepresentation [42, 44]. However, rural white men may not be underrepresented in all areas of research—for instance, they may be adequately represented in studies on substance use, agricultural health, and occupational medicine [38, 43]. Is he a member of an underserved population? Yes. Many rural areas lack nearby hospitals, specialists, and clinical trial sites. Long travel distances, limited provider availability, and fewer research opportunities create significant barriers to care [94]. Rural populations are disproportionately affected by physician shortages and reduced access to preventive care, making them underserved even when they are not explicitly categorized as vulnerable [42, 95].
Pregnant, white woman with elite private insurance	Is she a member of a vulnerable population? No, but she may face unique research protections. Pregnant individuals are not classified as a vulnerable population under the 2018 Common Rule update [5]. However, pregnancy introduces physiological changes that may increase health risks, and concerns about fetal safety often lead to heightened scrutiny and additional research safeguards [96]. Is she a member of a minority population? No. Pregnancy is a temporary condition rather than a demographic minority status. While pregnant individuals may experience unique healthcare challenges, they do not constitute a minority population in the way that racial, ethnic, or permanently marginalized groups do [9]. Is she a member of a population underrepresented in research? Yes. Pregnant individuals are routinely excluded from clinical research, leading to significant gaps in knowledge about the safety and efficacy of medications, treatments, and vaccines during pregnancy [13, 73]. This exclusion occurs due to concerns about fetal safety, legal liability, and ethical considerations [96]. The lack of research participation results in limited evidence-based guidelines, which can complicate medical decision-making during pregnancy [7]. Is she a member of an underserved population? No. With comprehensive private insurance, this woman likely has access to high-quality prenatal care, specialists, and advanced medical facilities. Unlike many pregnant individuals who may experience financial, geographic, or systemic barriers to maternal healthcare, she does not face restricted access to medical services [73].

3. Why Underserved Populations Should Be Included in Research

The continued exclusion of underserved populations from research is an ethical failure that must be addressed. Our argument here is that increasing the participation of these populations in research is essential to reducing health and health care disparities. We acknowledge that such disparities have many causes, and underrepresentation in research is only one. Tackling the problem of underserved populations will of course require accounting for social, economic, environmental, and structural factors. Yet, there are compelling ethical reasons for making inclusion in research a component of a multi-faceted solution. Therefore, throughout this discussion, we will address both underserved populations in healthcare and underrepresented populations in research, acknowledging that while these groups often overlap, they are not identical.

3.1. To Promote Justice in Research and Care

Concern for justice remains a core commitment of bioethics. Justice is often understood to be giving each person their due – ensuring that they have access to resources and opportunities that enable them to live healthy lives. While there is often an emphasis on just distribution of resources, we believe justice also demands dismantling systemic barriers [19].

When underserved populations are underrepresented in research, this limits their access to the benefits of research. These could be direct benefits (i.e., those that accrue to participants as a result of receiving a study intervention), indirect benefits (i.e., those that arise from participation, even if one does not receive the study intervention, such as a free health exam or feelings of being helpful), or benefits to society or future patients, particularly knowledge that results in improvements in health [20].

When underrepresented populations are recruited to participate in research, they may encounter disproportionate logistical barriers—such as transportation, financial, and time constraints—depending on the trial design. This can make participation relatively more burdensome for them than for other participants [21], and they may have trouble accessing resulting benefits (e.g., if the study results in approval of a new treatment). While our focus is on later-phase trials, Phase I studies raise ethical concerns as marginalized individuals—often due to financial hardship or limited healthcare access—are disproportionately enrolled in these high-risk, non-therapeutic trials and yet remain underrepresented in later-phase trials where they might benefit from effective treatments [22, 23].

This imbalance in the distribution of benefits and burdens contributes to less just research and to a less just healthcare system overall. By increasing the inclusion of underserved populations in research, we take a necessary step toward generating data that informs more equitable healthcare practices while expanding access to potential benefits [24].

3.2. To Increase Fairness in Research and Generalizability

Fair subject selection is a fundamental requirement of ethical research. Participants should not be excluded without a sound scientific rationale or justified concern for vulnerability. While justice in research demands dismantling systemic barriers, fairness refers to ensuring that the selection of research participants follows equitable processes that do not arbitrarily favor certain groups over others [25]. This includes making research participation accessible and ensuring that the burdens and benefits of research are equitably distributed in practice, not just in principle. Fair recruitment practices not only align with ethical obligations but also serve a distinct methodological purpose: safeguarding the rigor and validity of research by ensuring that study findings can be applied to a diverse range of populations.

However, research design decisions often result in patterns of underrepresentation that, while not intentionally exclusionary, systematically limit participation from underserved populations. For example, eligibility criteria that favor “healthier” individuals—while designed to minimize risk—can result in study samples that fail to reflect real-world patient diversity. Similarly, trial designs that require frequent in-person visits may impair participation by rural, disabled, or low-income individuals due to transportation and financial constraints. These are procedural fairness issues: while no group is formally barred from participation, the structure of research unintentionally privileges those who face fewer barriers. As a result, the very populations that stand to benefit most from medical research are often missing from the studies that shape healthcare practices.

The consequences of limited representation in research extend beyond individual access to participation. Without adequate demographic and clinical diversity, research findings may overlook meaningful heterogeneity in treatment effects, leading to biased conclusions and incomplete evidence [26]. This can compromise clinical decision-making, producing interventions that fail to meet the needs of certain populations or are even inappropriate for marginalized groups [27].

By framing fairness in research participation as integral to both generalizability and methodological rigor, we highlight its role in producing robust, reliable findings that support more just healthcare practices. While fairness in subject selection helps ensure equity in research processes, it also has broader implications for healthcare justice by generating the evidence necessary to provide effective care to all populations.

3.3. To Promote Trust in Research and Healthcare

Including underserved populations in research is also essential for fostering trust in medical research and healthcare systems. Mistrust is often attributed to historical ethical violations, but ongoing underrepresentation in clinical trials and disparities in access to medical innovations continue justifiably to reinforce skepticism. When marginalized communities remain disproportionately absent from research, it signals that medical advancements may not be designed with their needs in mind. Conversely, inclusion demonstrates that research is conducted for the benefit of all populations, not just select groups.

Beyond inclusion, how research findings are applied also influences trust. When study results are broadly applicable, they not only strengthen the scientific merit of the research but also increase its potential for meaningful public health impact [28]. This is especially important in later-phase trials designed to shape clinical guidelines and healthcare practices, where the results need to be disseminated widely and implemented effectively to maximize their benefit [29]. Inadequate dissemination or failure to apply these findings equitably risks making the research extractive rather than beneficial, which can exacerbate inequities and erode trust, as underserved populations may contribute to research without ultimately benefiting from its outcomes. If underserved populations participate in research but do not see tangible improvements in healthcare access and treatment, skepticism about the fairness and justice of research is reinforced.

Inclusion alone is not sufficient to restore trust—research must also lead to substantive changes in healthcare equity. When participation in clinical trials is coupled with efforts to ensure that findings inform accessible, high-quality care, it can help rectify both historical and ongoing injustices [10, 30]. This, in turn, reaffirms the legitimacy of medical research, strengthens its role in advancing equitable healthcare policies, and promotes long-term engagement from marginalized communities.

4. Achieving Inclusivity for Underserved Populations

Underserved populations are heterogenous, requiring context-specific strategies to achieve inclusivity in research [31]. Additionally, members of underserved populations may belong to multiple groups—for instance, someone may be both a racial minority and LGBTQIA+ or a disabled adult and rural resident. These overlapping identities can compound the barriers to research participation, meaning that solutions must account for intersectionality.

This section considers four underserved populations—rural, racial and ethnic minority, low-income, and older adult populations—exploring some of the unique barriers each group faces to research participation and proposing tailored solutions. While some barriers and solutions are shared across groups, we aim to show that each population experiences a distinct set of obstacles. Consequently, meeting the ethical obligation to ensure fair inclusion in research will require reflection on the nature of these obstacles and thoughtful solutions.

4.1. Rural Populations

4.1.1. Barriers

Rural areas frequently lack adequate healthcare infrastructure and trained professionals to conduct trials locally, limiting local research opportunities [32]. Thus, research is often concentrated in urban centers, far from where rural residents live. Long-distance travel to study sites is burdensome and often impractical, especially with limited transportation options [16, 33]. Financial constraints further complicate participation [34]. Those interested in research may find expenses associated with participation—such as the costs associated with travel, childcare, and lost income due to time away from work—prohibitive [35, 36].

The geographic isolation of rural populations also fosters mistrust in medical institutions by limiting regular interactions with healthcare providers. The consolidation of healthcare services in urban centers and the closure of rural hospitals have deepened this mistrust by reinforcing perceptions of neglect [37, 38]. Additionally, the opioid crisis, where healthcare providers were seen as complicit in overprescribing addictive medications, particularly for chronic pain, has worsened mistrust, as rural areas have disproportionately suffered from addiction and overdose deaths [37, 39].

These challenges hinder rural residents’ awareness of clinical trial opportunities and contribute to common misconceptions about participating in trials [16, 40, 41]. Rural residents often have less access to healthcare facilities where clinical trial information might be provided, and fewer interactions with research institutions, which limits their exposure to accurate information about clinical trials. This results in greater reliance on second-hand sources, hearsay, or media, which can contribute to misunderstandings [40, 41]. Moreover, rural healthcare providers often lack the time, resources, and support systems to proactively discuss clinical trials with patients, limiting awareness and reinforcing misconceptions about trial participation [41–44].

Furthermore, rural populations face higher rates of chronic illnesses, such as cardiovascular disease and diabetes, partly due to limited healthcare access, higher poverty levels, and lifestyle factors shaped by their environment [2]. Poor diet, higher tobacco and alcohol use, and occupational hazards in farming and mining may all contribute to or exacerbate these health issues [45–47]. This, in turn, leads to exclusion from clinical trials due to restrictive eligibility criteria, perpetuating a cycle where being underrepresented in research reinforces being underserved in healthcare.

4.1.2. Solutions

Expanding trial sites to community health centers and rural clinics as well as utilizing mobile health units is a key strategy to increase research accessibility for rural populations [44]. Research institutions can partner with such facilities or local primary care providers, while policymakers can support these efforts through funding and regulations [48]. Approaches increasingly seen in decentralized clinical trials, such as using telemedicine and remote monitoring, can further increase access while minimizing travel-related burdens [31, 36].

Addressing financial barriers is also critical, requiring the commitment of both industry sponsors and federal/nonprofit research funders. Long-term financial support and flexible funding models would help sustain accessibility initiatives, such as transportation services, stipends, childcare reimbursements, and participant compensation tailored to local needs. By prioritizing funding to enhance accessibility, industry sponsors and research funders can help ensure that rural populations have equitable access to clinical trials [36, 49, 50]. Researchers and community organizations can then integrate these resources into their recruitment efforts.

Broadening eligibility criteria is essential to ensuring fairness in the inclusion of individuals with common rural health conditions. While not suitable for every trial, doing so when appropriate can help ensure that research better reflects real-world patient populations and benefits those most affected [51, 52]. To encourage making trial designs more flexible and inclusive, funding agencies should continue—and consider expanding—efforts to integrate equitable recruitment practices into grant evaluations, ensuring that diversity, equity, and inclusion initiatives explicitly account for rural populations alongside racial and ethnic minorities [26, 30]. Making this an evaluation criterion should further enhance research opportunities and ensure broader inclusion.

In some cases, expanding rural trial sites may require balancing institutional risk tolerance with the need to support less experienced investigators. Research in rural settings is often conducted by clinicians who may have limited formal research training, raising concerns about oversight and ethical preparedness [53]. Sponsors and IRBs may need to weigh maintenance of traditional research oversight standards against the goal of increasing rural trial participation.

To build trust and encourage participation, researchers should engage communities through culturally relevant education and outreach. Industry sponsors and research funders can support these efforts by allocating resources for community engagement that leverages rural communication strategies, such as sharing information via local radio stations and agricultural supply stores where residents regularly gather in some rural communities [40, 44]. Sustained investment in community partnerships—including collaborations with healthcare providers, local coalitions, faith-based groups, and health departments—can foster credibility and ensure a consistent presence in rural areas [16, 33, 37].

While large-scale investments in local healthcare infrastructure, such as reversing rural hospital closures, might substantially improve accessibility, we recognize that such initiatives come with considerable economic trade-offs and logistical challenges. Nevertheless, policymakers, in collaboration with industry sponsors and funders, could explore targeted resource allocation for enhancing or reopening key facilities, especially where healthcare access gaps are most acute. These efforts would not only enhance research participation but also promote justice by addressing long-standing healthcare inequities the mistrust of healthcare institutions in rural communities [37].

4.2. Racial and Ethnic Minority Populations

4.2.1. Barriers

Racial and ethnic minority populations face multiple barriers to research participation, with a central issue being deep-seated mistrust. This mistrust is often attributed to the Tuskegee Syphilis Study [10, 54, 55]. It is important to acknowledge, however, that this wariness is also perpetuated by ongoing experiences of stigma and systemic bias within healthcare systems, which further deepen skepticism about researchers’ motives and the safety of clinical trials [51, 56].

Nevertheless, evidence suggests that minority groups are generally as willing as non-Hispanic whites to participate in research when informed of opportunities; however, they are often not made aware of these opportunities [57]. Implicit biases among health care providers and assumptions that minority populations may be less interested or may not adhere to study protocols can unintentionally limit recruitment efforts [26, 58].

Language and cultural barriers also hinder participation, especially for Hispanic and Asian populations who may not receive trial-related information in their preferred languages [11, 59]. Untranslated materials and a lack of culturally competent research staff further marginalize these groups, preventing their equitable inclusion in studies [3, 60, 61].

The collection of Social Security Numbers (SSNs) for tax reporting purposes when participants receive financial compensation can deter marginalized populations from participating [62, 63]. Because of privacy concerns, particularly among non-citizens or undocumented individuals (a majority of whom are Hispanic), requiring SSNs can serve as a procedural barrier rather than an equitable safeguard [64].

Additionally, racial and ethnic minority populations have a disproportionate burden of underlying comorbidities, such as hypertension and diabetes [65], which (as discussed above) frequently lead to exclusion from clinical trials with restrictive eligibility criteria [17].

4.2.2. Solutions

One strategy for improving racial and ethnic minority representation is the establishment of Community Advisory Boards (CABs), which can foster trust and promote procedural fairness by giving community members a voice in research decisions [10, 66]. This approach, which is seen as a more accessible starting point, can be further strengthened by Community-Based Participatory Research (CBPR). In CBPR, researchers engage community members throughout the research process, promoting both fairness in research procedures and trust in research outcomes [10, 30]. Partnering with trusted local leaders and organizations helps to make outreach efforts more culturally responsive and aligned with community needs[51, 59].

To enhance inclusivity, research institutions should consider implementing culturally tailored recruitment strategies. This may involve training staff in cultural competence and implicit bias to improve interactions with minority patients, and translating materials into multiple languages for greater accessibility, particularly for Hispanic and Asian populations [60, 61, 63]. Research teams should include racially and ethnically concordant researchers and staff—those who share the cultural and linguistic background of these participants—which can further build trust and promote fairness in recruitment [67, 68]. To support such efforts, long-term investments are needed to diversify the research workforce, with academic institutions creating pathways and training programs to support talent from underrepresented populations [54]. Funders can also support training grants.

Given the higher prevalence of chronic conditions like diabetes and cardiovascular disease in minority populations, researchers should carefully evaluate the necessity of restrictive eligibility criteria and consider broadening them, when possible, to promote fairness in participation. As mentioned above, funding agencies should continue integrating diversity and inclusion into grant evaluations to ensure that recruitment efforts not only follow fair procedures but also actively work to correct historical underrepresentation in research [11].

To address the barrier of collecting SSNs, we recommend that researchers limit SSN collection to cases where compensation exceeds a threshold that requires tax reporting, as some institutions may collect SSNs more broadly for administrative purposes, even when not strictly necessary. Institutional Review Boards (IRBs) could ensure that research protocols minimize unnecessary SSN collection, and policymakers could support these efforts by revising tax regulations to accommodate more flexible reporting options for research participants [63].

Culturally tailored education campaigns are also important for increasing health literacy and trial awareness. Delivered through relevant platforms like local media, community events, and trusted spaces, such campaigns help correct misconceptions and highlight the benefits of research [35, 40, 41]. Policymakers and funders could ensure resources are available to sustain and expand these initiatives.

4.3. Low-income Populations

4.3.1. Barriers

Low-income populations face significant barriers to research participation related to economic hardship, structural inequities, and limited healthcare access. Financial instability is a major obstacle, as individuals often cannot afford to take time off from hourly or informal jobs that lack paid leave to participate in research [69]. Additionally, transportation and childcare costs can make participation unfeasible, even for research that may offer the prospect of health benefit [49, 50].

As for rural populations, limited access to healthcare facilities complicates participation for low-income populations. Clinical trial sites are frequently located in affluent areas, far from low-income neighborhoods, and a lack of affordable transportation exacerbates access barriers [24, 34]. Even when trials are conducted locally, these areas often lack the necessary research infrastructure and personnel, making participation logistically challenging [36].

Insurance disparities also play a role, as many low-income individuals are uninsured or underinsured, reducing their touchpoints with the healthcare system and thus opportunities to learn about clinical trials [70]. Inadequate outreach often leaves these individuals unaware of research opportunities [61]. Further, researchers may hesitate to recruit low-income or uninsured individuals, assuming they cannot manage participation costs, even when trials offer free care [71].

Low health literacy is common in low-income populations and makes it difficult for individuals to understand the risks and benefits of trials, especially when recruitment materials are not appropriately adapted to a low literacy level [3, 58]. As with the populations discussed above, comorbidities are more prevalent in low-income populations, disproportionately excluding them from participation [2, 71].

4.3.2. Solutions

One approach for improving the representation of low-income populations is to provide financial support tailored to participants’ needs. Research funders like the NIH, as well as research institutions and industry partners, could consider allocating resources to cover transportation, childcare, and lost wages, developing flexible models that offset financial burdens while ensuring ethical standards are upheld [49, 69]. Additional strategies to promote accessibility include offering diverse payment methods, including cash or reloadable cards that do not require a bank account [62]. IRBs play a key role in approving participant remuneration and should be mindful of how compensation can encourage or discourage participation.

Expanding clinical trial sites within or near low-income populations is also worth considering. Partnerships with community health centers and safety-net clinics can bring trials closer to these populations and minimize barriers for uninsured and underinsured populations [36, 70, 72]. Mobile health units and decentralized clinical trial approaches such as telemedicine and home-based monitoring offer additional accessibility [34, 48].

Effective outreach within low-income communities can be achieved by partnering with trusted local organizations—such as community centers, housing programs, food banks, and faith-based groups—that can align recruitment strategies with residents’ immediate needs like employment security, childcare, and affordable healthcare [62, 63]. Research institutions can support these efforts by developing educational campaigns tailored to different literacy levels, aiming for an 8^th-grade reading level or below, and use accessible platforms such as local media and community events to promote awareness and participation [30]. As mentioned previously, sustaining these efforts will require the continued efforts to integrate diversity criteria into grant evaluations, expanding local healthcare services in low-income communities [34], and investing in training and diversifying the research workforce. To effectively reach low-income populations, researchers could receive training on securing resources for low-income participants, such as state or federal assistance programs, and on communicating study details clearly and without medical jargon.

4.4. Older adult populations

4.4.1. Barriers

Older adults face numerous barriers that limit their participation in clinical research. Many older adults are excluded from research due to strict age cut-off points and exclusion criteria that disqualify individuals with comorbidities, cognitive impairments, or those on multiple medications [2, 52].

Additionally, cognitive issues, such as dementia, can undermine older adults’ ability to provide informed consent [52, 73]. Although cognition and consent are not the same, the two are related, and consent-related concerns often lead researchers and IRBs reflexively to exclude cognitively impaired older adults.

Many older adults have reduced mobility, making frequent travel to trial sites difficult [74]. Inadequate transportation options and the physical strain of travel further discourage participation, even for those who express interest [48].

Low digital literacy is another barrier, as clinical research increasingly relies on digital tools like telemedicine and remote monitoring [75–77]. Many elderly individuals lack experience with these technologies, creating a digital divide that limits their engagement. Without adequate training and support, these individuals are left out of otherwise accessible research. While these digital tools can increase participation for some groups, such as rural residents, they may pose additional obstacles for older adults without adequate training and support.

Healthcare access disparities and mistrust of clinical research further reduce participation rates. Older adults, especially in underserved or rural areas, struggle to access routine care, let alone participate in specialized studies [34]. Historical exclusion from research has also fostered skepticism, leading some to view clinical trials as unsuitable for their age group [70].

4.4.2. Solutions

Broadening eligibility criteria is essential to include older adults with common comorbidities and health conditions. Incorporating geriatric assessments (GA), such as the Cancer and Aging Research Group (CARG) score or the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score, can help identify older adults who are suitable for trial participation by evaluating their functional status and resilience [78]. Given that industry-funded studies tend to include fewer older adults [79], it would be beneficial for regulatory bodies like the FDA to require pharmaceutical and medical device companies to include a minimum proportion of older participants in clinical trials, especially for conditions that disproportionately affect this age group [2, 52]. Additionally, when older adults are excluded from trials, IRBs can push for justifications to ensure exclusion is well justified or suggest alterations.

To overcome mobility barriers, researchers can conduct decentralized trials and utilize telemedicine or mobile health units that allow older adults to participate from home. Decentralized trials that allow participants to “bring their own device” (BYOD) may help accommodate older adults who are comfortable using their personal smartphones or tablets, reducing the need for unfamiliar trial-specific technology. However, these approaches should also account for individuals who lack personal devices or digital literacy by offering alternative participation options and providing adequate technical support.

Telemedicine platforms should be designed with accessible, user-friendly features, with trial site staff offering technical support, training, and home visits to assist participants as needed [30, 80]. Additionally, establishing trial sites at community centers, senior living facilities, and local clinics can bring research closer to older populations, while providing transportation services to support those with travel difficulties [48, 81]. To sustain these efforts, agencies like the NIH could allocate resources for decentralized trial infrastructure, transportation, and age-friendly technologies, ensuring these efforts are integrated into the broader clinical research framework for long-term sustainability.

To accommodate cognitive and sensory impairments, consent forms and informational materials should be simplified and visually accessible [80]. Research staff should be trained to communicate effectively with individuals experiencing hearing loss or vision impairment ensuring participants are well-informed [73]. If researchers anticipate working with cognitively impaired individuals, they should have plans for assessing capacity and identifying legally authorized representatives [78, 82]. Building trust through community partnerships is also important. Collaborating with organizations—such as the AARP, senior centers, assisted living facilities, local councils on aging, and advocacy groups—as well as trusted local figures—such as healthcare providers and social workers—can create outreach programs that engage older adults and address misconceptions, demonstrating how research participation can benefit their health [82].

5. Conclusion

Ensuring the inclusion of underserved populations in clinical research is ethically imperative. The distinct barriers faced by groups such as rural, racial minority, low-income, and older adult populations—ranging from geographic and financial obstacles to mistrust and lack of research awareness—require intentional, equity-driven solutions. These strategies must involve expanding access points, modifying trial designs, and building trust through community engagement. Addressing these barriers is not only an ethical imperative but also essential for producing research that is relevant to all populations, thereby enabling the development of effective, inclusive healthcare interventions. By prioritizing the representation of underserved groups, clinical research can better fulfill its mission of improving health outcomes equitably across diverse populations.