Disparities in Cancer Research: A Precursor to Disparate Cancer Outcomes
Overall cancer mortality has decreased in the United States1 thanks to tremendous progress in cancer prevention, early detection, and treatment—underpinned by decades of research progress.2,3
Unfortunately, not all individuals with cancer have benefited equitably from this success, as Blacks, patients living in rural areas,4 populations with lower income and education levels,5 and others continue to experience lower survival and higher mortality rates for many cancers.
“As clinicians, we are committed to providing evidence-based, high-quality cancer care to every patient, every day, everywhere. But, if clinical trials don’t represent the individuals we treat, including those from racial, ethnic, and other minority populations, the state of science suffers, and patients with life-threatening conditions may not receive the best— perhaps only—treatment option for their condition.”
—Lori J. Pierce, MD, FASTRO, FASCO, ASCO President, 2020-2021
Disparities in cancer outcomes are rooted, in some respects, in the development of novel diagnostics and therapeutics—the clinical research that demonstrates the efficacy and safety of new cancer treatments.
Although most patients express a willingness to participate in clinical research, only approximately 8% of adult cancer patients enroll in cancer clinical trials,11 and the percentage of minorities participating in clinical trials, overall, is much lower when compared to the general population of the United States. Blacks, Hispanics, and other minority groups, for example, continue to be underrepresented in clinical trials. Recent analyses of cancer treatment trials found that only 4%-6% of clinical trial participants are Black, and 3%-6% are Latino, despite representing 15% and 13% of all patients with cancer, respectively.12,13 The under-representation of minority groups in cancer research contributes to disparities in cancer care and outcomes by failing to provide the evidence that clinicians need to safely treat minority patients with cancer.
In contrast, progress in pediatric oncology tells a different story. With a greater than 50% enrollment rate of affected children, pediatric cancer clinical trials have always been more inclusive and diverse, contributing to a decline in pediatric cancer mortality rates over more than four decades, while the rate for adults has been declining for just the past two-plus decades.14
The COVID-19 pandemic may exacerbate disparities in cancer research, as the coronavirus has been yet another reminder of disparities in access to care and outcomes in the United States. COVID-19 took a greater toll with higher hospitalizations and death rates in American Indian and Native Alaskan, Black, and Hispanic communities,15 and among Black and Hispanic patients with cancer, in particular.16 Loss of employment and employment-based insurance coverage have also hit these communities the hardest, presenting additional barriers to participating in clinical research.
Disparities in cancer research is a complex multifaceted issue requiring a multifactorial response that addresses specific inter-related barriers that preclude certain populations from trial participation, as well as structural and systemic challenges that limit the cancer community’s ability to conduct research that would benefit underserved populations.
In August 2020, ASCO published its Cancer Disparities and Health Equity Policy Statement, which included a focus on ensuring equitable access to cancer research and stressed that all populations should have an equal opportunity to participate in, be recognized for, and benefit from research across the spectrum, including clinical trials, health services research, and other types of research studies and methodologies. The statement underscores that a collective effort by all stakeholders— including patients, caregivers, providers, policy leaders, pharmaceutical organizations, and advocacy groups—is needed to develop appropriately targeted approaches to achieve this goal.
Evidence Gaps in Health Disparities Cancer Research
Health disparities research is a foundational discipline that addresses population-based inequities in cancer research and crosses large areas of inquiry, including biologic and environmental determinants of cancer incidence; biologic, environmental, and system-level determinants of postdiagnosis survival; and social determinants of health. Spanning transdisciplinary fields, health equity cancer research integrates basic science, clinical science, policy, epidemiology, and the social sciences.
In 2017, four leading cancer organizations, the American Association for Cancer Research, the American Cancer Society, ASCO, and NCI, released a joint position statement entitled Charting the Future of Cancer Health Disparities Research.17 This statement presented a unified strategy to promote cooperation among investigators in all areas of cancer research to ensure that cancer research benefits all populations and patients regardless of race, ethnicity, age, gender identity, sexual orientation, socioeconomic status, or the communities in which they live.
The statement identified gaps in data available about patients and their communities. Routine collection and reporting of data regarding demographic and clinical characteristics of research participants can increase the likelihood that research will acknowledge and potentially address health disparities,18 including differences in treatment effectiveness, tolerance, and outcomes. Studies should routinely collect and publicly report aggregated data on demographic and clinical factors (including race/ethnicity, sexual orientation, and gender identity, nativity, ability status, socioeconomic status, age, comorbidities, and treatment, among others).
Another avenue for making research more inclusive is through postmarket data collection. Using a larger, more representative sample gives physicians and researchers the ability to generate new hypotheses and apply those insights to improve care in real-world settings. CancerLinQ, a real-world oncology data platform developed by ASCO, supports this goal by securely compiling, analyzing, and de-identifying vast amounts of information on patient characteristics using data from 1.5 million patients from across the nation in oncology practices of all sizes and settings.
Barriers to Equitable Cancer Research
Patients with cancer who might, otherwise, be candidates for clinical trials continue to face multiple barriers, which must be thoroughly understood and appropriately addressed before the cancer community can learn from every individual with cancer.
The barriers that patients face have been broken down into five categories:14
- Structural barriers—having access to a clinic or site offering a clinical trial, including factors such as transportation and its associated costs, health insurance status, and dependent care.
- Clinical barriers—a patient must be eligible to participate in a particular trial.
- Patient attitudes toward clinical trials—historically, patients often have reported being nervous about the idea of participating in a clinical trial, although educational efforts and easily understandable informed consent documents may mitigate this.
- Physician attitudes—while most oncologists agree that clinical trials are a high-quality option for many patients, many still fail to offer patients the opportunity to enroll in a clinical trial or treat their patients off-protocol rather than officially enroll a patient in the trial in an effort to not accrue additional administrative burden and regulatory liability.
- Demographic and socioeconomic disparities—the most common demographic disparity is age of the patient; race as a factor is more mixed, depending on the type of trial and disease being studied.
Other reasons for low participation rates for all populations range from trial eligibility that excludes patients with comorbidities, financial hardships, and patient misconceptions about clinical trials. When combined, these structural and clinical barriers make trial participation unachievable for more than three of four patients with cancer.19
Strategies to Improve Equity in Cancer Research
There are some strategies and actions that can be used to lower the barriers to clinical trial participation and thereby increase the pool of participants:
Eligibility criteria. One way to make clinical trials available to more patients while simultaneously gathering evidence from a wider swath of the population is to broaden trial eligibility criteria. ASCO and Friends of Cancer Research have worked to support the FDA in doing this, and in July 2020, the FDA finalized four new Guidance for Industry documents that recommended broadening eligibility criteria for clinical trials by lowering the minimum age to possibly incorporate adolescent patients and by including patients with brain metastases who have been treated and are stable, and not automatically excluding patients with active brain metastases or patients with leptomeningeal disease. The guidance documents also address inclusion of patients with HIV, hepatitis B, and hepatitis C, and patients with prior or concurrent malignancies and recommend less restrictive renal, cardiac, and hepatic function criteria. The FDA also released draft guidance to encourage greater trial participation by older adults, the population that experiences the majority of cancer diagnoses and deaths.20
More recently, the FDA issued final guidance that recommends approaches that sponsors of clinical trials can take to increase diversity in their trials—with an emphasis on real-world data.21
Umbrella and basket trial design. Another method by which to expand clinical trial participation is by using umbrella and basket trials, both of which can test several treatments at once across more than one cancer population simultaneously, which potentially could examine and compare the experience of underserved populations.22 An umbrella trial tests how well new therapies work in patients with the same type of cancer but different gene mutations or biomarkers. A basket trial tests how well a therapy works in patients with different types of cancers that have the same gene mutations or biomarkers. For example, ASCO’s TAPUR Study is a basket trial designed to learn from the greatest number of patients possible by having minimal eligibility criteria, which is possible because the study involves only FDA-approved, targeted drugs. This is different than most clinical trials, which have traditionally left out large swaths of the population and skew younger and healthier than the typical patient with cancer.
Trial availability. Geography presents yet another significant barrier in clinical trial enrollment, even after a match has been made between an ongoing trial and a patient’s cancer type and stage. A 2020 study published in the Journal of the American Medical Association examined the location of clinical trials relative to population and found that a lack of a convenient trial location explained 87% of disparities in clinical trial participants. This is especially true for patients in rural areas but even for those in more populous regions who lack ease of transportation to a particular site.23 The FDA’s 2020 final guidance noted previously also recommends sending medical professionals to visit trial participants instead of requiring extensive participant travel—a step that could appreciably address this barrier.
Concerns about trial availability also showed up in a 2020 study for the Oncology Nursing Society that found patients were willing and able to travel approximately 11 miles to a clinical trial site, with differences among ethnic groups. The study advocated that nurses could be a crucial element in understanding these geographic disparities and helping guide patients to relevant trials that would be feasible for them.24
Patient education, recruitment, and support. A recent ASCO survey25 found significant misperceptions among Americans about clinical trials. Nearly half of all respondents (48%) believe patients with cancer who participate in clinical trials are not receiving the best possible care, although clinical trials may offer the best options for initial treatment and, when the current standard of care is not working for a patient, they may provide a treatment option when no other treatments are available. Additionally, 75% of Americans, including 87% of patients with cancer, believe that some people who participate in cancer clinical trials receive a placebo rather than actual treatment—although placebos are rarely used in cancer clinical trials and are only used when there is no standard treatment available.
Increased physician-to-patient education and expanded community outreach could address this lack of understanding about the true nature of clinical trials. Researchers should be encouraged to use recruitment strategies that ensure adequate representation of populations afflicted with the disease being studied and those at risk of disparate outcomes, including, but not limited to, populations with diverse socioeconomic status, race/ethnicity, and geographic location (urban or rural). Social media and the use of patient-centered recruitment messaging is also gaining traction in assisting with recruiting patients for clinical research who may traditionally have been under-represented.18
Patient navigation. Other programs that have improved inclusion in research include patient navigation, educational efforts led by community health workers, and partnerships with community and advocacy organizations. Such efforts can assist with overcoming other known barriers to participation in research, such as transportation and childcare.
Novel consent strategies. Novel strategies include informed consent practices that are more accessible and understandable to participants from a wide range of cultural and linguistic backgrounds. Methods include multimedia consent content with concise text blocks, visual icons, and videos on smartphone-optimized web interfaces.18
Financial assistance. Although health insurance coverage of costs associated with clinical trial participation are, generally, covered by Medicare and private payers, Medicaid is not federally required to cover routine care costs (including physician visits and laboratory studies). With nearly 20% of Americans covered under Medicaid, a large swath of individuals with cancer—including those from under-represented minority and ethnic groups not well-represented in clinical trials—are financially unable to participate in potentially life-saving research.
ASCO has joined with numerous other organizations in urging Congress to pass the bipartisan CLINICAL TREATMENT Act, which would guarantee coverage of the routine care costs of clinical trial participation for Medicaid enrollees with life-threatening conditions. This legislation would improve the validity of clinical research data, thereby delivering better treatments to all patients while helping to reduce health disparities and ensure all patients have access to high-quality, high-value cancer care.
Discussion: Lessons From the Pandemic
The COVID-19 pandemic has provided a unique opportunity to re-envision cancer research and examine, in particular, disparities in clinical trials participation. Cancer clinical trials were upended in the early months of the outbreak, with widespread interruptions in trial enrollment preventing some patients from receiving experimental cancer therapies. Within the first weeks of the pandemic, some 60% of research institutions halted patient screening and enrollment for at least some trials.26 Similar numbers halted patient visits focused only on research, blood draws, or tissue collections, prioritizing only those visits that were essential to sustain patients’ health.
Yet, research sponsors and regulators acted quickly to create more flexible research practices averting a total shutdown of trials. The FDA and NCI quickly issued guidance and workarounds to give researchers and trial sponsors new flexibility while preserving the integrity of research. Along with remote patient monitoring and drug administration, the guidance allowed virtual consent using e-signatures, limited collection of research-only biospecimens, and blood draws or imaging scans done by local healthcare providers close to home. As a result, most patients were able to continue their treatments, and most trials were able to resume after just a few weeks or months of interruption.
The COVID-19 pandemic brought racial and other health disparities into sharp relief. At the same time, it was also clear that the healthcare system—and the oncology community in particular—has the agility to respond quickly to substantial and unexpected disruptions to both clinical trials and clinical care. This same ingenuity and flexibility can and should be applied to improving health equity for all individuals, so that the right treatment truly is delivered to the right patient at the right time, everywhere.