Increasing accrual in cancer clinical trials with a focus on minority enrollment
The William Beaumont Hospital Community Clinical Oncology Program Experience
Article first published online: 31 MAR 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 20, pages 4764–4771, 15 October 2011
How to Cite
Vicini, F., Nancarrow-Tull, J., Shah, C., Chmielewski, G., Fakhouri, M., Sitarek, S. A., Feczko, C. T., Brzozowski, C. and Felten, D. L. (2011), Increasing accrual in cancer clinical trials with a focus on minority enrollment. Cancer, 117: 4764–4771. doi: 10.1002/cncr.26094
- Issue published online: 5 OCT 2011
- Article first published online: 31 MAR 2011
- Manuscript Accepted: 14 FEB 2011
- Manuscript Revised: 8 FEB 2011
- Manuscript Received: 1 DEC 2010
- Cancer Clinical Trials Office at Beaumont Hospitals
- Administration of Beaumont Hospitals
- Beaumont Community Clinical Oncology Program (CCOP)
- community clinical oncology program;
- clinical trials;
- National Cancer Institute;
The authors reviewed changes in accrual to cancer clinical trials over the last 2 decades at their institution with a focus on minority participation after the implementation of a community clinical oncology program (CCOP) and an aggressive, education-orientated minority outreach program (MOP).
Data on patient enrollment in clinical trials for the years 1988 to 2010 was obtained from the William Beaumont Hospital (WBH) Cancer Clinical Trials Office. The type and number of cancers diagnosed and treated during the same period were obtained from the WBH tumor registry data. The MOP was initiated in the fall of 2003 with a focus on culture-specific cancer education.
With the development of the CCOP, clinical trials accrual increased significantly by 10-fold (P = .001). The primary service area for the CCOP consistently averaged an 85% to 90% Caucasian population. During the same period, the minority population for the service area remained stable between 8.8% and 10% and did not change significantly. From 1999 to 2004, the WBH tumor registry data demonstrated that minorities represented 8.6% of cancers registered, whereas the average yearly minority enrollment from 2002 to 2004 was 5.4%. After initiation of the MOP, minority accrual doubled to 11% by 2010 with stable minority demographics.
The current findings support the importance of a CCOP in supporting the accrual of patients to national clinical trials and increasing access to state-of-the art research. These data also strongly support focusing additional energy and educational efforts on targeting minority representation in clinical trials. Cancer 2011;. © 2011 American Cancer Society.
In 1983, the National Cancer Institute (NCI) initiated the Community Clinical Oncology Program (CCOP), the goal of which was to hasten the adoption of state-of-the-art oncologic care in community-based institutions.1, 2 This was prompted, in large part, by the recognition that greater than 80% of cancers in the United States are diagnosed and treated in local communities, and not at major academic centers.1, 2 The primary strategy adapted to link community-based oncologists to major cancer centers and thought leaders in the field was to conduct clinical trials onto which community-based oncologists could enroll patients. Most studies to date indicate that these programs have been successful in accruing patients to cancer-treatment clinical trials, with community-based physicians contributing approximately 33% of patients placed in investigational protocols.3 Statistics indicate that CCOPs have enabled patients and physicians to participate in clinical trials in over 60 major research centers in 34 states across the country, the District of Columbia, and Puerto Rico4; as clinical trials have advanced in scope beyond treatment trials, so has the breadth and scope of the CCOP. Since 1987, CCOPs have been required to participate in nontreatment-related research in cancer prevention, detection, mitigation of cancer symptoms, and cancer control research.5 Because minorities and underserved populations traditionally have underused cancer prevention and screening resources, this increase in scope has provided an avenue for the improvement in health care disparities by allowing for the resources of an organized CCOP to help increase minority and underserved awareness of these issues.
A review of the barriers that limit patient participation in cancer clinical trials has yielded 3 primary barriers: protocol-related, patient-related, and physician-related. The 10 most common barriers that physicians and clinical trial personnel face are concerns regarding the trial setting, dislike of the randomization procedure, discomfort with the idea of research, concerns regarding protocol adherence and complexity, concern regarding receipt of placebos, fears regarding potential worsening of side-effects with new treatments, belief that clinical trials are not to be used in serious diseases, fear of altered physician-patient relationships after enrollment, potential physician nonacceptance of enrollment in clinical trials, and (the most common) being unaware of trials availability.6 A review of elderly patients indicated their continued under-representation and barriers that included physician perception, eligibility age and functional criteria, lack of resources, and a lack of social support.7 Potential barriers in minorities mirror barriers for the general population but also include a lack of belief in the benefit of research, distrust in the scientific community, desire for minority physicians, potential socioeconomic issues, religious beliefs, and higher rates of comorbidities.8, 9
In 1999, a Cancer Clinical Trials Office (CCTO) was established at William Beaumont Hospital (WBH). The goals were to expand access to state-of-the-art national clinical trials across multiple specialties and to increase enrollment in clinical trials as an institution using the CCOP model. With regard to enrollment, a special focus was placed on increasing the enrollment of minorities and the elderly in clinical trials to help with the goal of creating clinical trial populations that are representative of the treatment population at-large. After successfully demonstrating the ability to enroll patients into national clinical trials, the first CCOP grant award was received by WBH for the period from 2002 through 2005. The Beaumont CCOP was then awarded continuing renewal for the following 5 years with recent completion of a second funding period. Despite the successes and improvement in the clinical trials infrastructure at WBH and in the United States over the past 3 decades, significant challenges remain. One challenge is to continue to increase community-based physician accrual. Although the development of the CCOP has increased community accrual, there is still a disparity, as 80% of the nation's cancer patients are diagnosed and treated in the community setting, yet only represent 33% of clinical trial enrollees.1-3 Another continuing problem has been improving access and recruitment of minorities to clinical trials.10-13 Currently, minorities enroll at rates less than Caucasians despite studies indicating that minorities are willing to enroll at the same rates.14 The concern with this is that the results derived from these skewed trial populations may not represent the results that would be obtained if a well balanced and representative population sample was obtained.
Recognizing these concerns, our institution initiated a Minority Outreach Program (MOP) in collaboration with local community-based organizations and targeted the Metropolitan Detroit area's 5 major ethnic/minority populations, including the African-American (AA), Arab-American and Chaldean (AAC), Hispanic/Latino, Native American, and South East Asian communities. The MOP was designed in such a way that the institution's resources were added synergistically to the community resources to provide culture-specific, bilingual cancer education, prevention, and screening information in a culturally competent manner with the ultimate goal of helping to decrease minority health care disparities and increase representation of these target groups in the clinical trials process.
This report chronicles the changes in clinical trial participation after the development of the CCOP at WBH. Furthermore, we focus on the impact of our MOP on reaching the undeserved to participate in oncologic education and the clinical trials process.
MATERIALS AND METHODS
Data on patient enrollment in clinical trials for the years 1988 through 2009 was obtained from the WBH CCTO and Research Institute (RI), and data on all cancer patients who were diagnosed and treated at WBH were obtained from the WBH tumor registry. Approval for this study was granted by the Human Investigation Committee (our local institutional review board) on October 15, 2010. The factors analyzed included year of participation, patient demographics (including race/ethnicity), physician specialty, type of clinical trial (treatment and control), and disease site represented.
Cancer Clinical Trials Office/Community Clinical Oncology Program
A CCTO was first established at WBH in 1999. At the initiation of the CCTO, the personnel consisted of a principal investigator, a program director, and a small cadre of research nurses and clinical research associates. Additional staff was used as the volume of studies, as well as the complexity and intensity of the studies grew with a focus on diversity in skills, background, and interpersonal ability. From the initial 7-member team, the staff has grown to a highly functional, diverse, and interdependent team of 27 individuals whose focus includes improving accrual to clinical trials and helping to improve elderly and minority representation in clinical trials. These objectives have been addressed primarily by using the CCOP model. WBH was awarded a $2.4 million grant for a CCOP in 2002 and received $4.9 million in 2005. The current competitive renewal has been approved with an award of $4.8 million. The 2010 to 2015 grant period will encompass the addition of 2 more sites to service the northeast and northwest sections of an underserved minority-based county, offering additional opportunities to provide service and increase clinical trial participation in an ethnically diverse population.
To address the 3 primary barriers identified above (physician-related, patient-related, and protocol-related), the CCOP staff developed processes to address each of these complicated sets of barriers. Physician-related barriers were addressed through 3 primary processes designed not only to inform physicians about clinical trials but to make them active participants in the clinical trials process. This was achieved by frequent educational and informational sessions with physicians from the medical oncology and radiation oncology departments. These meetings focused on open protocols and eligibility requirements and also provided a forum for physicians to suggest trials they were interested in bringing to the institution and to answer any questions or concerns physicians had regarding open protocols. Physicians were also provided with pocket handbooks, which divided open cancer clinical trials into subsites so that, before seeing patients, they could use the reference to identify appropriate trials. Finally, at the time of consultation, summaries listing trials open for the patient in question were placed on charts. The CCTO/CCOP leadership believed that these processes not only would help with physician-related barriers but also would help overcome the most common barrier to patient enrollment: a lack of knowledge regarding available trials. This was based on the belief that physicians who were educated in clinical trials would be able to best relay this information to their patients.
To address patient-related and protocol-related barriers, a 2-pronged approach using both the individual physicians and the CCOP staff was pursued. Physicians from medical oncology and radiation oncology services were educated to inform patients that enrolling in trials did not mean a change in the physicians who would care for them and that their decision to enroll or not enroll would have no impact on the physician-patient relationship. Furthermore, physicians were educated by CCOP staff to explain that enrollment in protocols would only enhance follow-up after the completion of treatment. Physicians also were encouraged to spend time with the patient discussing the historic nature of cancer clinical trials and explain that the standard of care today is based on the clinical trials of the past and that the benefits of research potentially are not only for the individual but for society at large. Once a patient expressed an interest in a trial, the CCOP staff would meet with the patient and go over a particular trial extensively. If randomization was needed, then the rationale was explained to the patient. CCOP staff routinely explained to the patient, along with physicians, how experimental arms differed from the standard of care and any potential additional side effects the patient may experience. Because a significant barrier was observed secondary to fear of placebos, if a placebo was part of a trial, then the patient would be advised regarding whether or not they would be receiving the standard of care and whether the placebo was only in place of a new therapeutic addition. To help with barriers in elderly and minority patients, the CCOP staff consisted of a diverse group that was trained to provide social support resources, including assistance with ensuring that clinical trials would be covered by insurance, arranging transportation, and providing patients with reminders for scheduled follow-up visits or testing, including telephone calls as needed.
Minority Outreach Program
A diversity program was initiated in 2003 to help address health care disparities in ethnic minorities. The goal of the program was to improve the disparity in cancer screening rates within ethnic minority populations compared with historic standards within Metropolitan Detroit and, subsequently, to develop programs that built on these increased screening rates to improve outcomes for the most common malignancies facing these communities (breast, prostate, lung, colon, and cervical cancers). To help determine and implement appropriate cultural and community solutions to barriers in receiving oncologic care, the Beaumont Cancer Institute's MOP worked in collaboration with community-based organizations from the Metropolitan Detroit area's 5 major ethnic/minority populations. Using a community-based, participatory process, WBH representatives worked with community leaders to develop culturally competent programs focusing on cancer prevention and screening as well as methods of diagnosis and treatment paradigms. The end result of these partnerships was a series of forums presented within each ethnic minority community. The initial forums focused primarily on breast and prostate cancer screening; however, additional programs were put in place that expanded the focus to include colon and cervical cancer screening and also began dialogues with members of the community regarding available therapeutic alternatives for each type of malignancy and the resources available for patients to obtain more information so that they could pursue treatment as soon as possible if necessary. Data regarding disparities in outcomes were highlighted at forums, and participating physicians emphasized that 1 solution would be a strong community resolve to pursue screening early and, furthermore, educate patients when it comes to treatment by seeking out advanced therapies and potential clinical trials. At these forums, focus also was placed on educating participants about the clinical trials process and what participation entailed for them. Members of the CCOP were present to help inform participants about the clinical trials currently available at WBH as well as the individual and societal/community benefits provided by participating in clinical trials. The success of the MOP in improving screening rates was published recently, and MOP forums leading to a relative increase in screening rates of 38.6% and 28.7% for breast cancer and prostate cancer, respectively, compared with historic controls of screening within minority populations.15
Baseline rates of clinical trial accrual before the development of the CCTO/CCOP were collected retrospectively. Beginning in 2002, the CCTO prospectively collected information regarding clinical trial patient accrual, including information on minority representation within clinical trials. Therefore, enrollment of minorities in cancer clinical trials was evaluated only for the years 2002 to 2010. From 2002 to 2004, a significant number of patients did not have their ethnicity documented; therefore, complete evaluation of minority enrollment was not possible for those years. However, a composite average from those years was calculated using all patients who had ethnicity documented. Comparisons of the mean number of patients enrolled in clinical trials before and after the development of the CCOP and between the numbers of minority patients enrolled were performed using 2-sided t tests. A P value ≤ .05 was considered statistically significant, and all statistical analyses were performed using SYSTAT (version 13.0; SYSTAT Software, Chicago, Ill).
Before initiation of the CCOP, 606 patients had been enrolled on active clinical studies in the previous 13 years. By 2009, patient enrollment had increased to an average of 439 patients per year. In total, 340 patients were enrolled on clinical trials in 2009; however, when registry studies were included (mainly genomics and patients with Barrett esophagus), this number increased to 1176 patients. These increases were observed in studies that addressed cancer treatment, prevention and detection, mitigation of cancer symptoms, and cancer control research.
Table 1 lists the enrollment by year for the years before and after development of the CCOP. The total number of enrolled patients was 606 in the 13 years before CCOP development and 3950 in the 9 years after CCOP development. The average number of patients enrolled per year increased from 46.6 ± 56.8 patients per year before development of the CCOP to 438.9 ± 289.3 patients per year after development of the CCOP (P = .001). The median number of accrued patients increased from 30 patients per year before the CCOP to 340 after CCOP development. The maximum number of patients enrolled in a single year increased from 221 before to 1176 after development of the CCOP (Table 2). A major reason for the increase in accrual during this period was the significant increase in the number of clinical trials available for patient enrollment. At the onset of the CCOP, 3 clinical trials were available, including 2 that were focused on cancer treatment and 1 that was focused on cancer control. By May 2009, 196 clinical trials were available, with 131 focused on cancer treatment, 2 focused on prevention, 3 focused on detection, 6 focused on symptom management, and 54 focused on cancer control. This increase over 10 years represents a 60-fold increase in available trials.
|Before CCOP Development||After CCOP Development|
|Year||No. of Patients Enrolled||Year||No. of Patients Enrolled|
|Variable||Before CCOP Development (1988-2001)||After CCOP Development (2001-2010)||P|
|Total no. of patients enrolled||606||3950|
|Mean no. of patients enrolled per y||46.6||438.9||.001|
|Median no. of patients enrolled per y||30||340|
Data were limited on elderly patient enrollment before development of the CCOP. However, from 2002 to 2010, the number of patients aged >65 years (range, 65-89 years) enrolled on cancer clinical trials ranged from 46 to 450 per year, and the percentage of total accrual ranged from 13.3% to 38.3%. The average elderly accrual percentage was 30.2%, which represents a 37.3% increase over historic controls based on a large number of National Cancer Institute of Canada (NCIC) studies.16 When patients aged ≥70 years were evaluated, the percentage of total accrual ranged from 6.8% to 21.9% with an average accrual of 17.4%. This represents a 33.8% increase in accrual compared with historic controls from the Southwest Oncology Group (SWOG) studies.17
Minority Enrollment in Clinical Trials Over Time
For the years from 1999 to 2010, the primary service area for the WBH CCOP consistently averaged an 85% to 90% Caucasian population. During the same period, the minority population for the 5 major counties affiliated with the CCOP remained stable between 8.8% and 10%, and there was no statistically significant change over time. From 1999 to 2004, Beaumont tumor registry data indicated 8.6% minority representation, whereas the average yearly minority enrollment at the WBH CCOP from 2002 to 2004 was 5.4%. This represents a 37.2% disparity from the minority representation within the tumor registry. After the inception of the MOP along with the CCOP, minority enrollment increased: the highest yearly enrollment was 15.2% during 2006-2007, and average minority enrollment was 10.2% (Table 3). There was a significant difference in average accrual during the years before and after development of the CCOP and MOP (P = .01). The percentage of each minority represented in the accrual numbers was consistent across the years the MOP was implemented, with 69.6% AA (range, 56.5%-76.7%), 16.5% Asian (range, 8.7%-31%), 1.3% Native American (range, 0-3.3%), and 12.6% Hispanic (range, 3.3%-21.7%). Data regarding accrual by minority group was not available before the introduction of the MOP, which prevented a comparison of the demographics.
|Year||Total No. Accrued||No. of Males||No. of Females||No. of Minorities (% of Total Accrual)|
The current report chronicles the changes in clinical trial participation that occurred over 20 years after the development of a CCTO, the awarding of a CCOP grant to our institution, and the initiation of an ambitious MOP. The number of clinical trials and patient accrual increased significantly over the period studied, as anticipated, with a nearly 10-fold increase in patients accrued per year. These increases were observed for studies that addressed cancer treatment, cancer prevention, cancer detection, mitigation of cancer symptoms, and cancer control research. With regard to the enrollment of elderly patients on cancer clinical trials, after development of the CCOP, rates of elderly enrollment were improved over the baseline rates reported in large cohorts of patients from NCIC and SWOG studies. Although data were not available regarding elderly accrual at our institution before the CCOP, we believed that the use of historic controls from large pools of patients would provide an excellent comparison because of the diverse nature of institutions accruing patients for NCIC or SWOG trials. Just as critical as the increase in elderly patient participation, accrual rates increased for minorities by greater than 100%. Before development of the CCOP and MOP, there was 37.2% disparity from the minority representation within the tumor registry; however, after the CCOP and MOP were developed, minority enrollment exceeded targeted goals based on expected enrollment rates relative to the proportion of these groups in our cancer population. Although some variability was observed in the rates of minority enrollment, all values were increased compared with the years before the CCOP and MOP were developed, and we believe the variation may be related to the opening and closing of specific trials that focused on malignancies with dissimilar ethnic minority incidence rates. However, these findings emphasize the importance of CCOP grant awards in supporting the accrual of under-represented patients to national clinical trials. However, they also emphasize that aggressive outreach still is needed to increase the enrollment of minorities, because the rates of minority enrollment increased only when the CCOP was combined with an aggressive MOP.
Advances in biomedical research are yielding significant opportunities to improve cancer prevention, detection, and treatment. However, the ability to translate biomedical discoveries into meaningful advances in cancer care depends on an effective clinical trials system. Often, publicly funded clinical trials play a major role by addressing questions that are important to patients but are less likely to be top priorities of industry. One of the CCOP strengths is the extensive involvement of physicians and patients from the community, which allows for the treatment of a diverse patient population in the community setting rather than treating only those patients who have access to large academic cancer centers. This helps to ensure that the results of clinical trials are meaningful to a broad segment of the US population. Also, this provides patients with access to promising, innovative therapies as they are developed and tested in a setting that often is more accessible than traditional academic medical centers. Clinical trials conducted by the cooperative groups also provide a valuable mechanism for training clinical investigators in the community setting on up-and-coming technologies and techniques. More recently, our CCOP also expanded to meet the needs of the expanding fields of genomics and esophageal cancer prevention. Contributions to the Michigan Department of Health Genomics Database for Breast Cancer and participation in a industry-sponsored database for radiofrequency ablation in patients with Barrett esophagus hopefully can dove tail in the future with NCI initiatives dealing with breast and esophageal cancers.
Despite the success of the clinical trials system in the United States, significant challenges remain. One concern has been increasing accrual to clinical trials in general and, more specifically, community-based accrual into large clinical trials. Currently, only 2.5% of the population enrolls in clinical trials.18 Data presented here support the CCOP model as a method to increase patient accrual in the community setting. Furthermore, the CCOP model allowed for many more cancer clinical trials to become available to clinicians, providing them with a more complete set of trials from which to choose. Before the CCOP was developed, 3 clinical trials were available; but, within a 10-year period, that number rose to nearly 200 clinical trials available.
Another major concern has been improving access and recruitment of the elderly and minorities into the clinical trials process, because they continue to be under represented.10, 11 The under represented continue to suffer from disparities with regard to cancer incidence, mortality, and cancer care.19, 20 It has been suggested that increasing minority and under-represented populations in clinical trials is a means to help reduce oncologic disparities.21 A recent review of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial indicated that eligible AA, Hispanic, and Asian patients enrolled in the study at rates that were far less than their Caucasian peers.22 Furthermore, a review of the Patterns of Care Study indicated that AA patients enrolled significantly less in radiation therapy trials than Caucasians.23 An evaluation of the reasons for the continued disparities was performed by Ford et al, who observed that minorities and under-represented populations continue to face multiple barriers and challenges that limit their ability to participate in clinical trials, as noted previously.24 Joseph and Dohan concluded that many of these barriers are institutional in nature and suggested that institutional involvement with under-represented communities could help to solve these disparities.25 It is our belief based on the results presented that a well organized CCOP can be the catalyst for removal of these barriers.
To address the cancer care disparities that continue to exist in metropolitan Detroit, the Beaumont Cancer Institute created the MOP. The program was designed to provide cultural-specific, bilingual cancer education and information on clinical trials participation, as noted above, with the ultimate goals of helping to decrease racial/ethnic health care disparities and increasing representation of these target groups in the clinical trials process. The program was structured to help break down barriers currently encountered by many within these vulnerable and high-risk target populations. Because of the multiple outreach educational events targeted to diverse groups in our community, thousands of minority patients were provided education and resources on oncologic screening, prevention, diagnosis, and care. They also were provided with resources to access care. The current study demonstrates that targeted enrollment goals (based on expected enrollment rates relative to the proportion of these groups in our cancer population) have easily been exceeded, and minority enrollment in clinical trials improved by more than 100% after the inception of the MOP. In terms of comparisons with previous attempts to increase minority enrollment, our results compare favorably. A previous study indicated that an enhanced media campaign improved registration by 3-fold compared with standard methods, and another study indicated that the use of church-based information dissemination along with increased amounts of contact improved enrollment compared with standard methods.26, 27
The benefit of the MOP went beyond simply enrolling patients in clinical trials. For example, from 2005 through 2008, 2281 AA and AAC members participated in outreach efforts (cancer education, prevention, and screening forums) conducted by the Beaumont Cancer Institute and MOP in cooperation with the Arab American and Chaldean Council, the NCI, and the American Cancer Society. Because they attended at least 1 cancer forum, 329 of 1067 (30.8%) participant respondents (questionnaires) underwent some type of cancer screening, including 108 women (13.9% of woman respondents) who underwent a screening mammogram, 94 women (12.1%) who received a Papanicolaou smear, 38 men (13.1%) who underwent prostate-specific antigen screening, and an additional 89 participants (8.3%) who underwent some other form of cancer screenings (eg, colonoscopy). Overall, 32% of AA respondents and 28.9% of AAC respondents underwent some type of cancer screening, which represents a significant improvement over historic controls. Therefore, results of the MOP suggest that focused educational outreach can play a major role in successfully recruiting these challenging subsets of patients into making important health care decisions. Furthermore, focused educational outreach can help address the disparities among minority and under-represented populations with regard to clinical trials. Currently, what remains a challenge is how best to provide these underserved populations with health care resources so that they can more easily act on the education provided during the MOP.
In conclusion, the results of this analysis emphasize the importance of CCOPs in supporting the accrual of patients to national clinical trials; after the development of a CCOP, enrollment in clinical trials increased 10-fold. Furthermore, with integration of the CCOP with a MOP, enrollment of minorities in clinical trials doubled in a short interval. Despite these significant improvements, aggressive outreach is still needed to increase the enrollment of minorities by addressing barriers through focused, community-based participatory processes.
We thank the staff of the Cancer Clinical Trials Office at Beaumont Hospitals, the Administration of Beaumont Hospitals, and the Beaumont Research Institute for their support of the Beaumont Community Clinical Oncology Program (CCOP). We also acknowledge and thank Pamela A. Williams, RN, MSN, for her invaluable work with Beaumont CCOP.
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
- 15Strategies for reducing cancer incidence and mortality in African American and Arab American and Chaldean communities in the Detroit metropolitan area. Am J Clin Oncol. In press., , , et al.
- 21Institute of Medicine, Board on Health Sciences Policy. The Unequal Burden of Cancer: An Assessment of NIH Research and Programs for Ethnic Minorities and the Medically Underserved. Washington, DC: National Academies Press; 1999.