Special Issue: Clinical Trials Enrollment
Taking Action to Diversify Clinical Cancer Research
Many decry the fact that only 3 to 5 percent of adults with cancer in the United States join clinical trials, but a deeper challenge emerges when you put faces to these numbers. Close to 90 percent of those who do enroll in NCI-sponsored studies are white (with Hispanics/Latinos accounting for only 5.6 percent of that amount).
Rural State Networks Link Patients to Clinical Trials
Another example of innovative ways to enhance recruitment in the community setting is the Midwest Cancer Alliance (MCA), a network of 14 institutional partners (universities, health system clinics, hospitals) throughout the state of Kansas and in western Missouri that collaborate with the University of Kansas Cancer Center.
“We’ve been using telemedicine for over 15 years to reach out to the community and provide care close to home,” explained MCA Medical Director Dr. Gary C. Doolittle. “It’s a core part of our mission.”
About 20 percent of Americans live in rural areas, facing common challenges such as less access to care and awareness of clinical trial opportunities. Patients throughout Kansas can enroll in cooperative group and pharmaceutical trials, which are traditionally available only in urban cancer centers, through the MCA. In most cases, they can complete all trial activities without the burden of travel.
“Minority, rural, elderly, and other underserved patient populations bear a heavy burden of cancer disease but remain underrepresented in clinical trials,” says Dr. Jean Ford, from Johns Hopkins Bloomberg School of Public Health. “Not only does this pile one disparity atop another by denying them the benefits of clinical trials as a treatment option, but it potentially compromises the ability to generalize trial results to those groups.” (See the sidebar on rural populations.)
NCI is using several approaches to increase the enrollment of minority and underserved patients in clinical trials. In 2001, the Institute established the Center to Reduce Cancer Health Disparities (CRCHD), in part, to address the problems minorities face in gaining access to cutting-edge cancer care, including the care provided in clinical trials.
“The reasons for cancer health disparities can be complex and unique to specific populations and include behavioral, environmental, and biological factors,” said CRCHD Director Dr. Sanya Springfield at the recent National Minority Quality Forum Seventh Annual Health Disparities Leadership Summit. CRCHD, she added, is funding numerous programs to help train a diverse cadre of investigators to effectively deliver cancer advances, such as those afforded by clinical trials, to diverse and underserved communities at risk for or with poor outcomes.
Dr. Derek Raghavan, director of the Cleveland Clinic Taussig Cancer Institute, agrees that training a diverse clinical trials workforce is critical. He co-authored a recent American Society of Clinical Oncology (ASCO) policy statement on disparities in cancer care. “Improving the proportion of minorities who are recruited into the oncology clinical specialties is a big part of our strategy for increasing minority representation in cancer clinical trials,” he said.
Enrollment at the Community Level
One of the most successful dedicated NCI programs to date for improving minority enrollment in clinical trials is the Division of Cancer Prevention’s Minority-Based Community Clinical Oncology Program (MB-CCOP). Over the past 20 years, the MB-CCOP has worked to help community oncologists who serve large minority populations recruit patients to NCI-sponsored clinical trials at cancer centers, university centers, and community programs. Between 2000 and 2008, MB-CCOP researchers helped recruit nearly 7,000 minority patients in cancer treatment, prevention, and control trials. In fact, nearly two-thirds of all clinical trials participants recruited in the 14 MB-CCOPs are minorities. In 2007, NCI’s Board of Scientific Advisors called on NCI to use the MB-CCOP as a model for its other programs that need greater accrual of minority patients.
Dr. Steven Wolff is director of the MB-CCOP at Meharry Medical College in Nashville, TN, where a shared resource was established at the Nashville General Hospital at Meharry (NGHM) in collaboration with the Vanderbilt-Ingram Cancer Center. This resource is the product of a pilot study funded by CRCHD’s Comprehensive Minority Institution/Cancer Center Partnership program. The program’s goal is to develop and evaluate a model that enhances recruitment and retention of African Americans in national cancer clinical trials.
This program is unique in defining and prioritizing clinical trials that are relevant to the African American patient base at NGHM, Dr. Wolff said. Data on all patients diagnosed with cancer at the hospital are entered into a database, and a nurse navigator is assigned to each patient for follow-up. Procedures are established and customized for each step in the recruitment process, and a research or clinical staff member is assigned to ensure that the step is completed.
After testing and refining the model, 68 percent of those who were eligible to participate in a clinical trial––61 percent of them African American––agreed to take part in one, explained Dr. Wolff. “These accrual rates are more than double those reported in the literature. We attribute our success to a proactive approach, adequate resources, additional time and effort allocated for the informed consent process, decreased logistics, and cultural sensitivity of the research staff.
Community Engagement and Patient Navigators Boost Trial Enrollment
Working closely with the Hispanic/Latino community and assisted by a trained, bilingual patient navigator, investigators from the CRCHD-supported Community Networks Program (CNP), Redes En Acción increased enrollment into pediatric hematology/oncology clinical trials in a South Texas county with increased rates of childhood leukemia.
The Redes En Accion program used a multipronged approach—featuring a Spanish-speaking navigator, community outreach and education, and an enrollment tracking tool—to increase by 48 percent the number of Hispanic/Latino children accrued to local hematology clinical trials. NCI’s Coordinating Center for Clinical Trials helped fund the effort.
“This was a most impressive result,” said CNP Redes En Accion principal investigator, Dr. Amelie Ramirez, “and speaks to the importance of community involvement combined with the promise of navigation to help increase enrollment among some of our most vulnerable populations.”
Success in tackling the complexities of increasing clinical trials accrual for chronically underserved populations requires a broad array knowledge, abilities, sensitivities, and resources, say experts in the field, because the issues involved transcend race and ethnicity.
“It’s not just race per se,” explained Dr. Ford, of Johns Hopkins, “but rather how sociodemographic factors––such as age, gender, socioeconomic status, income, education, culture, language, and geography, as well as race and ethnicity––influence the process of accrual.”
To look deeper into that process, Dr. Ford’s group conducted a systematic literature review of barriers to recruiting minority and underserved patients to cancer clinical trials. From the 65 studies that met the criteria for review, they culled 150 discrete factors that act as barriers to accrual of underrepresented groups.
Dr. Ford developed a conceptual model that sorts the accrual process into three stages and demonstrates that barriers often differ by stage. Initially, patients must become aware of the role and concept of clinical trials in general. Barriers at this stage include lack of education about clinical trials, lack of physician awareness, and, to a lesser extent, knowledge about the origins of cancer.
Then, they need to learn about relevant opportunities to join specific trials. Barriers at this stage include other illnesses (comorbidities), age, race, inadequate health insurance, lack of provider referral, and socioeconomic status (including income).
Finally, they have to decide whether to enroll. Here barriers include the perceived risks of the treatment and practical concerns such as the time commitment, loss of income, transportation, and loss of control.
Creating Awareness, Building Opportunities
A proven strategy to raise awareness is to focus on the communities where target populations live and work. At Baylor College of Medicine in Houston, Dr. Armin Weinberg leads the Eliminating Disparities in Clinical Trials (EDICT) project. “Addressing any national health concern requires a systematic approach that provides assistance not only directly to individuals, but also promotes change at community, organizational, local, state, and national levels,” Dr. Weinberg said.
After producing policy recommendations to reform the trial enrollment system, Dr. Weinberg and his colleagues took EDICT researchers into eight local communities across the U.S. and engaged local stakeholders in regional community dialogue meetings. These meetings have led to ongoing activity and infrastructure that enhances that community as a context for clinical trials awareness.
Once patients become aware of clinical trials, the next stage is to match patients with clinical trials for which they are eligible. The NCI Community Cancer Centers Program has developed a process for tracking patients through this process and identifying factors that influence enrollment decisions. Using a Clinical Trials Screening and Accrual Log, hospitals in the network capture race and ethnicity data for all incoming cancer patients, as well as the reasons why patients who are screened for a trial may not join.
“A great example of the value of having strong baseline and tracking data is our new Underserved Patient Navigation Project,” explained Maria Gonzalez, cancer research manager at St. Joseph Hospital in Orange, CA.
At each site, navigators focus on particular cancers (breast, colorectal, etc.) and work closely with those research teams. The navigators disseminate clinical trials information to newly diagnosed patients, assess their needs, and refer appropriate patients for screening.
“Our goal is to have every member of their cancer care team educate the patient about clinical trials,” explained Ms. Gonzalez. “When their treating physicians approach them, most have already developed a good understanding of clinical trials, and that eliminates the ‘fear factor.’
“Our physicians like it because the stage is set for an effective and collaborative meeting over informed consent, reducing the time physicians have to spend on general clinical trials education and emphasizing trial and treatment options,” she said.
Deciding to Enroll
When making their final decision, patients seem to perform a kind of personal calculus of perceived risks and benefits, according to the Hopkins model, including factors such as trust in the trial’s sponsor/investigator, monetary costs, transportation, time, provider-related issues, culture, fear, family considerations/issues, religious/spiritual beliefs, altruism, and stress.
“This is not ‘one size fits all,’” cautioned Dr. Raghavan. “Most factors, both barriers and promoters of accrual, assume a different level of significance depending on which group you are targeting. Perhaps one of the most important issues is for the majority population to care about this issue and to establish real mechanisms to improve access to care and recruitment to trials where appropriate,” he added.
Drs. Ford, Raghavan, and Wolff co-led a discussion on “The Science of Minority and Underrepresented Accrual” at the recent NCI/ASCO Clinical Trial Accrual Symposium, where conference attendees agreed that targeting specific barriers can improve the situation. “But we have a long way to go,” said Dr. Ford, “and our systematic review of the literature suggests that it is past time for a unified national program that will generate the evidence needed to establish a standard of care that improves population diversity within cancer-related trials.”