Addressing the Social Determinants of Health to Enhance Clinical Trial Participation

Introduction

Notwithstanding the evident advances in cancer screening, detection of disease, and treatment options, health disparities in cancer care and treatment remain the leading cause of life-years lost in the United States. This trend continues to plague minority populations at an inequitable rate compared with their counterparts. Overcoming these iniquities will not be easy but can be obtained by approaching clinical trials through a lens committed to the social determinants of health. Achieving this goal will require that interventions are implemented consistently and equitably across all populations of persons.

The clinical trial mechanism for evaluating patients with similar stages and patterns of disease is the most powerful approach available for evaluating the efficacy of novel therapies. Clinical trials are foundational pillars for enhancing cancer care and treatment worldwide. In addition, clinical trials afford the ability to discover optimal interventions and treatment plans for the population. However, such interventions and treatment plans are only effective if all races and ethnicities are represented.

A British Medical Journal commentary once stated, “Good surgeons know how to operate, better ones when to operate and the best when not to operate.” The requisite platform for clinical trials in the surgical field inculcates the prior quote. One surgeon at The Ohio State University College of Medicine asked a single question of every medical school who entered the operating room: Whom does this patient live with/who is in the home with them? It was a question that frustrated even the most astute medical student who had spent the entire evening studying the branches of the internal iliac artery but failed to look at their social demographics in the patient's chart. Shifting our singular focus from pathology and physiology to a holistic approach illuminating the importance of the social determinants of health will be critical in achieving health equity and bridging the gap in health disparities.

In 1993, Congress enacted the National Institutes of Health (NIH) Revision Act to ensure the appropriate inclusion of women and members of racial and ethnic minority groups in all NIH-funded clinical research. The primary goal of this mandate was to ensure that research findings could be generalizable to the entire population. With a growing minority and ethnic population in the United States, this has increased relevance. Since 1993, the appropriated funds for clinical trials have increased over the past decades, although an increase in minority participation has not. As part of the Revitalization Act, prominent cancer support and funding organizations such as the American Cancer Society and Susan G. Komen for the Cure aggressively advocate for augmented outreach to minority communities for clinical trial participation. Inclusive clinical trials are the only proven strategy to date, proving the safety of new cancer treatments to improve standards of care. However, less than 5% of all eligible adult patients enroll in oncology clinical trials. Furthermore, of those enrolled persons, only approximately 14% are members of minority populations. According to Unger et al., from 1956 to 2016, in the Southwest Oncology Group Research Network, 12,361 patients were enrolled in 23 trials. The study estimated a 3.34 million life-years (95% CL, 2.39–4.15 million) were gained from the 23 trials through 2015. The fundamental elements of clinical trial design—standardized delivery of care and follow-up for novel treatments—are essential to make meaningful advances in the fields of surgery and medicine.

Current Data and Literature on Clinical Trial Participation

Advani et al. conducted a study with 218 patients with malignant disease (72 African Americans and 146 white patients) who were interviewed with a standardized survey. Results demonstrated a willingness to participate in a clinical trial depending on clinical site and race. 45% of White patients, compared with 31% of African American patients, were willing to participate in a clinical trial. There was no difference in percentages between the White and African American patients regarding patients who had heard of a clinical trial, knew what a clinical trial was, or had been asked to participate in a clinical trial. Overall, 40% noted they were willing to participate in a clinical trial, 22% were unwilling, and 39% were undecided. It is positive to see such a discrepancy between those willing and those unwilling to participate. However, undecided persons are where the focus of researchers, patient navigators, and recruiters needs to place their attention.

Recognizing the low numbers of racial and ethnic minority clinical trial involvement despite national efforts, Fayanju et al. performed a case–control study examining disparities in clinical trial participation among breast surgical oncology patients. The American College of Surgeons Oncology Group (ACOSOG) is a surgically based clinical trials cooperative group funded by the National Cancer Institute of the National Institutes of Health. The enrollment of African American and Latino patients from the ACOSOG clinical trials was congruent with the burden of cancer in these populations. Women with breast cancer enrolled in National Cancer Institute-sponsored, cooperative-group trials from 2000 to 2012, and who underwent oncologic surgery (n = 17,125) were compared with trial-eligible women in the National Cancer Database diagnosed in 2000–12 (n = 792, 719). Results demonstrated that from 2000 to 2003, Asian-Pacific Islander, Hispanic, and White patients from the highest-income groups had greater participation than their lower-income counterparts. From 2008 to 2012, only high-income White patients participated more than their lower-income counterparts. Blacks and Latino patients were much less likely to participate than Whites. However, high-income Black patients were 50% less likely to participate than White patients demonstrating statistically significant area-based patient income associated with clinical trial participation. The accrual of African American participants was 7.4%. When evaluated by site, participation rates for African American patients were 5.7% for thoracic studies, 8.6% for breast studies, and 11.6% for colorectal studies. The accrual of non-White Latino/a patients was 2.2% (0.6%—thoracic, 3.7%—breast, 5.8%–colorectal).

Fayanju et al. recently evaluated zip code–level data from patients included in the CTEP Surgical Oncology Trial Database to identify population-level determinants of participation in breast surgery trials. Patients from the highest area-based income bracket (>$63 000) were less likely to participate than those from the lowest-income bracket (<$38 000: OR = 0.63, 95% CI = 0.59–0.68). Furthermore, the likelihood of enrollment declined with increasing income ( P < .001). The impact of underrepresentation on clinical trials is critical for two reasons. First, if the sample size of participants is small, the results cannot be generalized to the entire population. Second, per the National Cancer Institute, the severity of cancer among minorities is prevalent. Definitive data and novel treatments are needed to improve cancer survival rates and reduce treatment side effects. This will only be accomplished if the understood barriers are overcome.

Barriers to Participation in Clinical Trials Underlying the Social Determinants of Health

There have been substantial barriers to minority participation in clinical trials. Murthy et al. summarize them as follows: minorities are more likely to express concerns regarding exploitation, dishonesty, and mistrust surrounding the motivation of the researchers, minorities are less likely to be offered clinical participation compared with their white counterparts, and disproportionately low-income facing potential minority participants can hinder appropriate and timely follow-up. In 2019, 116th Congress and Representative Elijah Cummings approved Bill H.R. 1966—Henrietta Lacks Enhancing Cancer Research Act of 2019. This act directed the Comptroller General of the United States to complete a study on barriers to participation in federally funded cancer clinical trials by populations traditionally underrepresented in such trials. For over 20 years, the advances made possible by Henrietta Lacks' cells, who died in 1951 from cervical cancer, were made possible without her or her family's consent. The generous revenues were not shared with or made known to her family. In conjunction with the Tuskegee Study of Untreated Syphilis in the Negro Male,” there is a legacy of mistrust and doubt surrounding researchers and clinical trials among minority communities.

From 1996 to 2002, approximately 3.1% of trial participants were Hispanic, 85.6% were White, 9.2% were Asian/Pacific Islanders, and 0.3% were American Indians/Alaskan Natives. This lack of participation from minority groups evidences the known litany of barriers to patient participation in clinical trials. Addressing the social determinants of health (SDH)—the environments where people are born, live, learn, work, play, worship, and age—may reduce such barriers. Creating a society where most persons are considered healthy and may successfully navigate cancer, and other chronic illnesses necessitate clinical trials (discoverable interventions and treatments) representative of the general population. This will require the further analysis of several areas of health policy as it pertains to barriers to clinical trial participation: decreasing food deserts in urban areas, augmenting the quality of free education, safeguarding persons from toxic exposure, providing equitable access to healthcare regardless of transportation option or the lack thereof. Education and income are the two main factors more detrimental to one's health than any other determinants. Furthermore, being poor, unemployed, or socially stigmatized may eliminate potential trial participants in studies pivotal to the population they represent. African Americans and Hispanic Americans are overrepresented among the impoverished and underinsured resulting in less likelihood they will have access to private/university/academic centers where clinical trials are more commonly offered. Most AA and HA patients often receive their healthcare at safety-net institutions.

Literature shows that even in randomized clinical trials, patients with Medicaid or no insurance may not contrive the same benefits associated with experimental therapies as patients with private insurance. If underinsured patients are unequal in the survival benefit from experimental therapies, a refocus on the social determinants of the patients is required. Inspection of their caregivers, communities, treatment teams, and health access before and after interventions might address the observed discrepancy. ^, The Delaware Cancer Consortium (established 2002) focused on the reduction of disparities within colorectal cancer outcomes statewide have implemented a nurse navigator system, screening reimbursement for low-income patients, cost coverage for uninsured patients who receive a positive diagnosis, and targeted community interventions to address disparities among the African American subpopulation.

Low participation in cancer clinical trials has become more common. This may be attributable to the rising cost of cancer care, a lack of transparency from insurance companies, and the perceived institutional impediments to patient financial support. ^{, , , ,} Moreover, the participation of diverse patients is tantamount to the discovery and implementation of therapies and interventions. Hindering such achievement has been found in the socioeconomic status of persons and other factors underlying the social determinants of health. Educational barriers among clinicians and patients also open the chasm between a heterogenous and exclusively homogenous population. Financial toxicity is another factor that has been studied and found to disallow patients from enrolling or continuing with participation in a clinical trial.

Implicit bias—associations outside conscious awareness that lead to a negative evaluation of a person based on irrelevant characteristics—displayed by a healthcare provider may significantly impact clinician–patient interaction. Fitzgerald and Hurst performed a systematic review of 42 articles demonstrating that physicians display similar bias to the broader population. Furthermore, a significant positive relationship was found between the level of implicit bias and lower quality of care. Addressing implicit bias among providers is requisite for creating an equitable environment. Implicit biases often disadvantage those already vulnerable—minority populations, immigrants, the poor, low health-literacy individuals, children, the mentally ill, and the elderly.

The consortium for Enhancing Minority Participation in Clinical Trials (EmPaCT), established in 2009 at five national cancer institutions, was designed to systematically address the limited enrollment of minorities in cancer clinical trials. From a series of reviewed and analyzed questions, five themes were found: (1) interactions with potential minority participants viewed as challenging, (2) potential minority candidates perceived to be nonideal study candidates, (3) clinic-based barriers in conjunction with negative perceptions of minority study participants by investigators led to providers withholding clinical trial opportunities from potential minority candidates. (4) when clinical trial recruitment practices were tailored to minority patients, addressing misconceptions to build trust was a common strategy, and for some providers, race was viewed as irrelevant when screening and recruiting for clinical trials.

Effective pathways can only be discovered and reproduced if the problem is understood or acknowledged. Naranjan et al. concluded that despite best intentions to provide equal clinical trial access to all patients' disparities in clinical trials persisted and may lead to increased morbidity and mortality for individuals underrepresented in the trials.