Participation in therapeutic clinical trials rarely reflects the race and ethnic composition of the patient population. To meet National Institutes of Health-mandated goals, strategies to increase participation are required. We recently reported our work from Siteman Cancer Center and the Program for the Elimination of CancerDisparities to increase trial participation.
Clinical trials are crucial to advancing science across the cancer continuum. Comprehensive inclusion of diverse participants in clinical trials is essential to assuring generalizability of prevention, diagnostic and treatment recommendations and ultimately the identification of effective treatments for all sectors of society. Although federal mandates require investigators to demonstrate sufficient representation of minorities in study samples 1-4, there continues to be disparity in the representation of racial and ethnic minorities in clinical trials 5-10.
Data available from 2000 show that accrual to National Cancer Institute-sponsored clinical trials for African Americans, Hispanics or Latinos, Asian/Pacific Islanders and American Indians was 8.2%, 4.5%, 1.8% and 0.3%, respectively 5. An update for the period 2003 to 2005 indicates that NCI and publically funded phase 1, 2, and 3 trials showed a national average of 8% African American participants among the total enrollment. Addition of Asian Pacific Islander (2.8%) and Native American Alaska Native (0.5%) and multiple (.1%) brought the total minority participation by race to 11.4% 11.
For all aforementioned groups except American Indians, clinical trial accrual percentages are considerably lower than each group’s respective make-up of the United States population (12.3%, 12.5%, 3.7% and 0.9%, respectively) 12. Additionally, other groups have been under-represented in clinical trials, including uninsured and underinsured adults, adults with lower socioeconomic status, and those living in underserved or rural areas 8,13-15.
Factors that contribute to this disproportional representation are well-documented and are influenced by multiple levels of interaction in the clinical trial recruitment process. In a recent paper, our team at Siteman published a report of our initiative through the Program for the Elimination of Cancer Disparities (see report). We present a framework for institutional enhancement of minority clinical trial accrual.
Four interrelated levels interact to influence enrollment of minorities to clinical trials. They range from individual level influences on patient trial participation (e.g. mistrust of research, faith beliefs, or fear of side effects) to interpersonal level factors (e.g. physician-patient relationships/communication or communication about trials between patients and friends or other patients) to institutional and clinical practice level influences (e.g. organizational infrastructure to reinforce minority recruitment, lack of physician awareness of available clinical trials, systemic lack of time for recruiting, or small minority patient pools), and finally, community and public policy level influences (e.g. federal mandates or inhibitive inclusion criteria that restrict participation due to a range of factors including co-morbidities) 16-31.
These discrete, but interrelated obstacles clearly indicate opportunities for intervention including careful consideration of required inclusion and exclusion criteria 19,32-35; structured evaluation of cancer trial results on strata such as age (or ethnicity) to understand tumor biology, treatment tolerability and the effects of comorbid conditions to help refine mandatory eligibility criteria for future studies 36,37; targeted patient communication via patient trusted communication vectors 38; use of peer coaches 39; and increased trust building between patient/provider and with communities 40,41.
Such interventions are essential in the path to achieve federal mandates for minorities in clinical trials. Emphasis is usually placed on individual and interpersonal levels of influence respective to both patients and providers. While this approach has merit and is part of the solution 42, closer linkage across levels of influence from individual to policy will speed attainment of minority clinical trial recruitment benchmarks over time. Sorensen et al. 43 illustrate this approach for cancer health behavior interventions across social contexts, and for achieving population-wide health advances in the United States 44. Without this linkage, interventions focused on individual and interpersonal levels of influence to increase minority participation are disconnected from parallel interventions at the community and public policy level of influence.
Consequently, an implementation gap results, which diffuses both progress toward and accountability for reaching national recruitment benchmarks, and makes way for slower progression of science discovery reinforcing poorer health status and quality of life for the population.
Fundamental to making the link across the continuum from individual to policy levels of influence is a focus on institutional level influences. Usually, there is an absence of any formal structure for ongoing monitoring of organizational/institutional progress in minority recruitment, beyond cancer center wide reporting at competitive peer review. To bridge this disconnect and underscore centralized accountability, tracking and monitoring across an organization, systematic adjustments to improve organizational infrastructure for minority clinical trial enrollment are required. Here, we describe a framework for centralized organizational accountability through systematic benchmark development, continuous progress monitoring and responsive adjustments at provider and organizational levels to enhance organizational infrastructure to induce and sustain increased minority participation in clinical trials.
Just how did we do this?
We implemented structural changes on four levels to induce and sustain minority accrual to clinical trials: (1) leadership support; (2) center-wide policy change; (3) infrastructural process control, data analysis, and reporting; and (4) follow-up with clinical investigators. A Protocol Review and Monitoring Committee reviews studies with 15 or more patients accruals as the target, and monitors accrual, and the Program for the Elimination Cancer Disparities leads efforts for proportional accrual, supporting the system through data tracking, web tools that allow investigators to see the average distribution of cancer by stage and race over the preceding 3 years, and provides feedback to investigators.
What did we find?
Following implementation in 2005, minority accrual to therapeutic trials increased from 12.0 % in 2005 to 14.0 % in 2010. The “rolling average” minority cancer incidence at the institution during this timeframe was 17.5 %. In addition to therapeutic trial accrual rates, we note significant increase in the number of minorities participating in all trials (therapeutic and nontherapeutic) from 2005 to 2010 (346-552, 60 % increase, p < 0.05) compared to a 52 % increase for Caucasians.
What dies this mean?
Implementing a system to aid investigators in planning and establishing targets for accrual, while requiring this component as a part of annual protocol review and monitoring of accrual, offers a successful strategy. We believe this approach can be replicated in other cancer centers, and may also extend to other clinical and translational research centers.
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