Equitable Representation of Latinos in Clinical Research Is Needed to Achieve Health Equity in Cancer Care

Abstract

PURPOSE:

Identify key barriers that keep Latinos from participating in clinical trials (CTs) and interventions proven effective in increasing their representation in clinical research.

METHODS:

Utilize our own extensive research experience and review the literature to: identify key barriers, summarize strategies that have been proven effective in increasing Latino representation in CTs, issue a call to action for programs/practices and practitioners to implement what is proven effective, and make recommendations for further research to address current gaps.

RESULTS:

Participation barriers are complex, multifactorial, and exist at different levels, including study design (eg, protocol complexity, patient exclusion criteria, trial duration and frequency), healthcare system barriers (eg, lack of minority staff), patient-related factors (eg, lack of awareness, low health literacy, language, social determinants of health [SDoH]), and medical team issues (eg, lack of cultural competence, lack of referrals, implicit bias, provider/patient communication). Research has shown that the most effective strategies to increase participation of underrepresented minorities in CTs include culturally sensitive educational tools aimed at community members, patients, and physicians, and strategies to address the multiple SDoH and other barriers to participation facing cancer patients and the factors that influence patient decision-making.

CONCLUSION:

Raising awareness or offering clinical trials to everyone will not alone increase Latino participation. Other key barriers at different levels must also be addressed, especially SDoH and patients’ contextual factors. To achieve equitable participation of Latinos and other underrepresented groups in clinical research, comprehensive approaches that address interrelated multilevel and multifactorial barriers to participation can produce a substantial, sustained impact—ensuring everyone equitably benefits from scientific advances in cancer treatment, improved cancer outcomes and quality of life, and reduced health care costs.

INTRODUCTION

Cancer is a major public health problem, especially for Latinos and other racial/ethnic minorities who experience a disproportionate burden of associated morbidity and mortality compared with other groups.^1-3 Despite this heavy burden, racial/ethnic minorities are less likely to participate in cancer clinical trials (CTs) and biobanking compared with their non-Latino White counterparts.^1,4-6

Knowledge gained through clinical research has proven critical to preventing, diagnosing, and treating cancer of various types, and providing the evidence base for clinical best practices.^4,7 Major advances in cancer treatment, which are essential for improving patients' outcomes, are derived from investigations of new therapeutic agents in CTs. As we move toward more individualized, personalized medicine, biospecimen research and biobanking are leading to more effective prevention, diagnosis, and treatment. In fact, current scientific advances in precision oncology are revolutionizing cancer care, and personalized treatments are improving cancer outcomes.⁴ However, these advances have not been equally enjoyed by all racial/ethnic minorities.⁸ Participation of historically under-represented groups in clinical research remains persistently low and does not represent the demographic diversity of the US population.^8,9 Fewer than one in 20 adult patients enroll in cancer CTs despite the large number of available studies and improvements in public awareness about clinical research.^10-12 In particular, recruitment of certain patients—racial/ethnic, sex, and sexual minorities, socioeconomically disadvantaged, rural, and older patients—has not increased as expected over several decades.^4,13,14 Their lack of inclusion and representation leads to overgeneralization of findings from non-Latino White populations to all racial/ethnic populations. From the health equity perspective, lack of CT participation among under-represented groups reduces opportunities for discovering effects that may be relevant to these groups and their cancer care, often preventing them from getting access to potentially lifesaving cancer treatments.^4,8,9

Although Latinos represent 19% of the nation's population,¹⁵ < 7% participate in CTs and only 2% participate in biobanking, resulting in many patients potentially missing out on access to breakthrough treatments.^16-20 The lack of Latinos and other under-represented groups in CTs also hinders the assessment and understanding of potential differences in drug efficacy and tolerability among diverse populations.⁹ These issues highlight the need for evidence-based interventions to improve participation of Latino patients in clinical research.^13,14,21,22

BARRIERS TO PARTICIPATION

Barriers to participation in CTs, biospecimen research, and biobanking are complex, multilevel, and multifactorial, including study design (eg, protocol length and complexity, patient exclusion criteria, trial duration, and high frequency of office visits), health care system barriers (eg, lack of minority staff), patient-related factors (lack of awareness, low health literacy, language, and social determinants of health [SDoH]), and medical team issues (eg, lack of cultural competence, lack of referrals, implicit bias, and provider/patient communication).^{4,7,17,18,23-26} Below, we describe in more detail patient-related and medical team–related barriers and include examples of evidence-based interventions that have been successful in addressing barriers at different levels.

Patient-Related Barriers

Some of the most frequently cited patient-related barriers that keep Latinos from participating in clinical research include lack of awareness and clear information about clinical research participation, lack of communication of results, lack of knowledge about disease and treatment options, lack of understanding about CT processes (ie, random assignment), and treatment preference.^23,24,26 Fear of pain or harm, distrust of the medical system, and attitudinal barriers (ie, fear of unknown reactions and side effects, the possibility of sacrificing quality of life, fear of being a guinea pig, and feelings of lost control),^23,24,26,27 may deter Latino patients from participating in research or considering CTs as a treatment option for cancer.^23,24,26,27 In addition, other deterrents among Latinos are cultural and language barriers, lower levels of health literacy, practical barriers related to SDoH (eg, lack of transportation, lack of health insurance, financial toxicity, and lack of family support), and study design barriers (eg, trial duration and high frequency of office visits).^18,20,23,24 Among SDoH barriers, Latinos have the highest uninsured rates among racial/ethnic minorities—with an estimated 19% of US Latinos uninsured—which poses an additional challenge for this population in attaining health care and participating in CTs.^28,29 Another important SDoH barrier among Latinos is financial toxicity, which has been recognized as an important driver of cancer treatment-associated burden for patients. Low-income and uninsured patients often deal with competing social and financial demands taking priority over their treatment, including decisions on whether to participate in a CT. The cumulative financial toll of out-of-pocket expenses can have a devastating and long-term effect on patients with cancer and their families.³⁰ Financial toxicity and its related stress can also have a direct impact on quality of life and cancer outcomes.^30,31 Multiple strategies have been suggested to address financial toxicity, including health policy changes to standardize insurance coverage for CT treatment, financial navigation and support, travel/transportation, lodging and parking coverage by trial center, and even normalizing noncoercive financial support to participants.³¹

Medical Team–Related Barriers

Research has shown that physician-patient communication barriers may deter physicians from offering CT enrollment to racial/ethnic minority patients.^1,25 This is of particular importance for Latinos because physicians are a trusted source of medical advice and information for this population, and a physician recommendation is one of the primary reasons cited by patients for their decision to participate in clinical research.^1,24 In addition, patients with low education and low literacy may not feel empowered to ask questions or initiate a discussion with their doctor regarding CTs.¹ A study exploring barriers and factors influencing patients' decisions to enroll in early-phase clinical trials and physician-related factors influencing the referral of patients to early-phase clinical trials showed that fears and uncertainty, as well as belief in the possibility of symptom improvement, were all associated with greater odds of not enrolling in CTs.^24,25,32 Doctor-patient communications are clearly a process of mutual influence affecting patients' decision making; therefore, interventions to promote CT participation among Latino patients need to directly address both patients and physicians.^2,33 Poor communication, coupled with structural inequities and bias in health care settings, put Latinos and other under-represented groups at an even higher risk for worse cancer health outcomes while widening existing disparities.¹⁸ Latino physicians were significantly less involved in CTs than their White peers, which has implications for whether they recommend them to their patients, according to a cross-sectional survey with 695 randomly selected physicians, stratified by race/ethnicity.¹⁸ Among physicians, logistical barriers for enrolling patients to CTs is a main deterrent to recommending CTs to patients.^24,25,32

Implicit bias among health care providers is increasingly recognized as an important barrier to diversity and inclusion of Latinos and other under-represented groups in CTs.^18,34 In a systematic review conducted by Hall et al,³⁴ researchers found that close to 70% of health care providers held moderate levels of implicit bias toward Latinos. Although not always overt, implicit bias may cause providers to hold negative attitudes toward patients of under-represented groups (eg, not offering CTs under the preconception that they will not comply with the study protocol), which causes them to refrain from discussing all possible treatment options for these patients, further exacerbating existing health care disparities.^18,34 Numerous studies have shown that implicit bias affects treatment decisions, which has negative effects on health outcomes for Latinos.^35-39

Despite these barriers, research demonstrates that minority patients, including Latinos, are as willing to participate in clinical research as non-Latino Whites.^40,41 In addition, a systematic review found that Latinos were the same or more likely to contribute to a biobank than non-Latino Whites and African Americans (odds ratio = 3.4; 1.0-11.3).^42,43 These data indicate that a lack of awareness and other key barriers are keeping these patients from participating. Most patients with cancer experience higher levels of anxiety, depression, and feelings of loss of personal control when facing a life-threatening disease such as cancer.^44,45 After diagnosis, cancer patients receive a lot of information regarding treatment options, including CTs, which can be quite complex, but is necessary to understand and process before making an informed decision regarding a course of treatment. In addition, the nature of the cancer care system involving multiple specialties, providers, and locations produce fragmentation and represent a challenge for the coordination of care for patients who frequently get lost in the system.⁴⁶ Therefore, to gain a greater understanding of how racial/ethnic minority patients respond to new treatments at the molecular level and to address Latino cancer health disparities, culturally relevant efforts to address CT participation barriers among patient and providers are needed to ensure equitable, inclusive recruitment of under-represented racial/ethnic populations.⁴

STRATEGIES TO INCREASE EQUITABLE PARTICIPATION OF LATINOS IN CLINICAL RESEARCH

To address low participation of under-represented population groups in CTs, the National Cancer Institute and the ASCO Clinical Trial Symposium recommended a combination of approaches. These include culturally sensitive educational tools aimed at community members, patients, and physicians, as well as strategies to address the multiple barriers to participation that patients with cancer face and the factors that influence patient decision making (eg, patient navigators (PNs), videos, websites, and printed materials).⁴⁷ Prior studies show that effective strategies to increase minority CT recruitment and retention involve community-based approaches that include community education and outreach activities, building social networks with minority organizations and community providers, and facilitating community engagement in cancer research.² In particular, culturally tailored CT communications and transparency can promote trust,⁴⁸ increase awareness, and improve attitudes, acceptance, and consideration of CTs as a treatment option for cancer, which in turn can enhance recruitment efforts among under-represented groups.²

Interventions providing decisional support, such as educational videos, and patient navigation (a recognized care coordination strategy) for patients addressing common barriers and facilitating the provision of coordinated patient-centered care, have been effective in improving positive attitudes toward CTs, accrual, and retention,^7,17,49-51 and may be feasible strategies to address low participation rates among Latinos and other under-represented groups.

Patient navigation has proven effective in supporting timely access to cancer care to minority patients including Latinos by addressing specific barriers and facilitating quality of care; care coordination by patient navigation has shown to have multiple benefits to the medical team, patients, and their families.^25,52,53 A systematic review on patient navigation found low rates of refusal to participate in CTs among under-represented patients receiving navigation services, with several studies reporting increased CT enrollment because of navigation.^49,52,54-56

In addition, several studies have effectively used educational videos and patient navigation as decision aids to increase patients' intent to enroll and enrollment into cancer CTs. A large, randomized trial conducted by Meropol et al⁷ found that, compared with a control group, patients assigned to an educational intervention with a video library addressing common barriers showed significantly greater increase in knowledge (P < .001), greater decrease in attitudinal barriers (P < .001), and a trend toward greater preparedness to consider CT participation (P < .09). A study by Du et al⁵⁷ found that, among 126 patients with lung cancer who had not previously participated in a CT, an educational video intervention was significantly associated with patients' self-assessed likelihood to enroll measured at 2-week follow-up (P = .019). In a similar study using a culturally sensitive video intervention aimed at African American patients with cancer, the intervention was effective in increasing patients' likelihood of enrolling in a therapeutic cancer CT (P < .001).⁵⁰ A recent prospective cohort study conducted by Cartmell et al assessed the effect of an intervention involving patient navigation and an educational video on CT participation among patients with lung and esophageal cancer. The results showed that navigated patients' CT understanding significantly improved between preintervention and postintervention (P = .004), and 95% of navigated patients consented to participate in a CT (95% CI, 82 to 98).⁵⁶

In addition, a randomized pilot study of a bilingual multilevel intervention (Choices) to empower Latina patients with breast cancer to make informed decisions about CTs, which included an educational interactive video, a low-literacy booklet, and care coordination by a PN, found that the Choices intervention was more effective than the control in improving perceived understanding of CTs (P .033), and increasing consideration of a CT as a treatment option for cancer (P .008). In addition, intervention participants showed significant changes between baseline and postintervention on agreement with stages of decision readiness statements (P < .002) than control participants (P > .05); the percentage of intervention women in agreement with preparation to action statements increased from 52.8% at baseline to 86.1% at postintervention, and those in agreement with ready to action stages rose from 50% to 88.9%.¹⁷

Providing patients with clear, easy-to-understand information and enhancing their decision-making process through decisional support aids, while facilitating care coordination and addressing common barriers to timely cancer care, fosters a sense of control and provides patients with the information and skills they need to make informed decisions regarding their treatment options and the resources to implement those decisions, resulting in more involvement in their physician-patient interaction, asking more questions about their treatment options, and assuming an active role in decision making.^17,19,58-61

A study by Fischer et al, using close patient navigation support to encourage Latino patients with advanced stages of illness to participate in a CT, showed improved participation and retention in the study at higher rates than previous cancer-focused palliative care intervention trials, overcame common CT participation barriers through the rapport built between Latino patients and PNs, and increased participants' self-efficacy in discussing their health with their doctor.^59,60 Although the researchers noted that these methods were time-consuming and required additional costs to the research budget, patients were more likely to participate and continue to participate in CTs if PNs called/texted regularly, visited the patient homes for study visits, and worked flexible hours (evenings and weekends) to accommodate the patient and their caregiver.⁵⁹ Understanding the importance of involving Latino patients' family members in the informed consent process and further study visits was an important strategy for participants to trust the study staff and continue their involvement in the CT.^59,60

Other studies have also shown that Latinos prefer receiving culturally tailored information about CTs and biobanking in video format, as well as via printed materials and in face-to-face presentations, with study participants stating that the tailored materials were the factor that influenced CT participation.^19,61 Culturally tailored educational videos on CTs are not only well received by Latinos and other under-represented groups, but also can increase their knowledge and intent to participate in CTs.⁵¹

Educational videos that include peer modeling and narrative messages from individuals who have participated in CTs and that are similar to the population groups they intend to reach can create a sense of commonality and trust in the message compared with strictly informational videos, providing another key strategy that can improve Latino participation in CTs.^17,51

An innovative but not-yet-fully-maximized method to improve recruitment in clinical research is the use of social media platforms to promote awareness of CTs, dispel misconceptions about clinical research, and enable researchers to engage community members and potential participants in unique ways.⁶² Targeted messages on social media platforms can stimulate interest in specific CTs that connect patients, caregivers, and advocates with trial centers' websites.⁶² In this area, Salud America! (SA!), a national, Latino-focused communication network, is creating and disseminating culturally relevant and evidence-based research outcomes, role model hero stories, educational and motivational videos, and action tools for grassroots health policy and system changes that address SDoH, health disparities, and CT participation.⁶³ For example, SA! is creating Latino-focused write-ups and infographics on CTs that are actively recruiting diverse participants locally (in South Texas) and nationally, as well as writing, filming, and uplifting the stories of Latino CT participants who serve as peer role models to encourage consideration of cancer CTs as a treatment option. This content is disseminated to a 500,000-strong network of community leaders across the nation through social media, a website, and e-mail distribution.⁶³ SA! also engages community and health care stakeholders via #SaludTues tweetchats on CT-related topics; tweetchats are a once-a-month, hour-long discussion series on Twitter, which have proven to be a powerful tool for public health practitioners and advocates to engage audiences on Twitter around health issues, advocacy, and policy solutions for Latino health equity.⁶⁴ Other studies have proven successful in improving recruitment of hard-to-reach populations into research by using Facebook advertising that used culturally appropriate graphics and messages on its target audience's preferred platform.^62,65 A similar example included targeted advertisement developed on the basis of users' online behavior, interests, and connection.^62,66

ASCO issued specific recommendations to improve health equity in cancer research participation. These include, among others, improving access by establishing more general CTs eligibility criteria and designing more pragmatic and efficient protocols, implementing policy and system changes to cover CT-related costs covered by health insurance, financial assistance programs for travel, lodging, and parking to reduce CT participants' out-of-pocket expenses, and improving the diversity of the cancer care workforce.^4,67 Having culturally competent medical teams that understand Latino cultural values (eg, familismo, respeto, and sympatia) is essential to establish a positive and bidirectional provider-patient relationship, build trust, and engage patient in communication regarding clinical research. The current COVID-19 pandemic affected CT participation but also highlighted the need to leverage technology and online platforms (ie, telemedicine and Zoom) to connect remotely with patients, facilitate their participation, and reduce related burdens for under-represented and geographically isolated patients.^48,67,68 This technology can be used for CT patient recruitment, informed consent, assessment of patient end points, and adverse events.^67,68

Raising awareness or offering CTs to everyone will not alone increase Latino participation. Other key barriers at different levels must also be addressed. To have equitable participation of Latinos and other under-represented groups in clinical research, it is recommended that clinical practitioners and health care programs implement multilevel interventions involving strategies proven to be effective in improving the representation of Latinos in CTs, such as using patient navigation, social media and digital or multimedia tools, and ensuring the cultural competency and diversity of medical teams. Further research is warranted to assess the impact of comprehensive approaches that address the inter-related multilevel and multifactorial participation barriers (health system, study design, health care provider, patient's individual, contextual factors, and SDoH) to produce a substantial and sustained impact. Such research could lead to the identification of best practices to implement evidence-based and culturally appropriate interventions for equitable enrollment and retention of Latinos and other under-represented groups in clinical research, which allows for the assessment and understanding of differential effects in outcomes of therapies on biologic and genetic characteristics. This will ensure everyone equally benefits from the scientific advances in cancer treatment, ultimately improve cancer outcomes, quality of life, and reduce health care costs associated with cancer-related morbidity, disability, and mortality.

ACKNOWLEDGMENT

The authors would like to thank Cliff Despres for his assistance in editing the manuscript and Gabriella Godines and Vivian Cortez for their support in reviewing the literature.

AUTHOR CONTRIBUTIONS

Conception and design: All authors

Collection and assembly of data: All authors

Data analysis and interpretation: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Equitable Representation of Latinos in Clinical Research Is Needed to Achieve Health Equity in Cancer Care

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).