Friday, July 19, 2013

Reducing cancer disparities through participating in clinical research

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.


1. Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH Revitalization Act of 1993--the perspective of NIH clinical trials. Control Clin Trials. Oct 1995;16(5):277-285; discussion 286-279, 293-309.
2. Hohmann AA, Parron DL. How the new NIH Guidelines on Inclusion of Women and Minorities apply: efficacy trials, effectiveness trials, and validity. J Consult Clin Psychol. Oct 1996;64(5):851-855.
3. NIH Revitalization Act of 1993. Vol PL 103-43June 10, 1993.
4. Amendment: NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research - October 2001. Vol NOT-OD-02-001 October 9, 2001.
5. Christian MC, Trimble EL. Increasing participation of physicians and patients from underrepresented racial and ethnic groups in National Cancer Institute-sponsored clinical trials. Cancer Epidemiol Biomarkers Prev. Mar 2003;12(3):S277-S283.
6. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. Jun 9 2004;291(22):2720-2726.
7. Stewart JH, Bertoni AG, Staten JL, Levine EA, Gross CP. Participation in surgical oncology clinical trials: gender-, race/ethnicity-, and age-based disparities. Ann Surg Oncol. Dec 2007;14(12):3328-3334.
8. Baquet CR, Ellison GL, Mishra SI. Analysis of Maryland cancer patient participation in national cancer institute-supported cancer treatment clinical trials. J Clin Oncol. Jul 10 2008;26(20):3380-3386.
9. National Cancer Institute. NCI-Supported clinical trials: facts and figures. [Website]. 2000; NCI clinical trials: an overview. Available at: Accessed 12 December, 2008.
10. Movsas B, Moughan J, Owen J, et al. Who enrolls onto clinical oncology trials? A radiation Patterns Of Care Study analysis. Int J Radiat Oncol Biol Phys. Jul 15 2007;68(4):1145-1150.
11. Springfield S. Racial and Ethnic Minorites Accrual to NCI Clinical Trials. Bethesdda, MD: Center to Reduce Cancer Health Disparities, National Cancer Institute, NIH;2010.
12. U.S. Bureau of the Census. DP-1. Profile of General Demographic Characteristics: 2000. Census 2000 Summary File 1 (SF 1) 100-Percent Data: U.S. Census Bureau; 2000.
13. Sateren WB, Trimble EL, Abrams J, et al. How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials. J Clin Oncol. Apr 15 2002;20(8):2109-2117.
14. Elliott TE, Elliott BA, Renier CM, Haller IV. Rural-urban differences in cancer care: results from the Lake Superior Rural Cancer Care Project. Minn Med. Sep 2004;87(9):44-50.
15. Klabunde CN, Springer BC, Butler B, White MS, Atkins J. Factors influencing enrollment in clinical trials for cancer treatment. South Med J. Dec 1999;92(12):1189-1193.
16. Ford JG, Howerton MW, Bolen S, et al. Knowledge and access to information on recruitment of underrepresented populations to cancer clinical trials. Evid Rep Technol Assess (Summ). Jun 2005(122):1-11.
17. Tournoux C, Katsahian S, Chevret S, Levy V. Factors influencing inclusion of patients with malignancies in clinical trials. Cancer. Jan 15 2006;106(2):258-270.
18. Ford JG, Howerton MW, Lai GY, et al. Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review. Cancer. Jan 15 2008;112(2):228-242.
19. Adams-Campbell LL, Ahaghotu C, Gaskins M, et al. Enrollment of African Americans onto clinical treatment trials: study design barriers. J Clin Oncol. Feb 15 2004;22(4):730-734.
20. Holcombe RF, Jacobson J, Li A, Moinpour CM. Inclusion of black Americans in oncology clinical trials: the Louisiana State University Medical Center experience. Am J Clin Oncol. Feb 1999;22(1):18-21.
21. Baquet CR, Commiskey P, Daniel Mullins C, Mishra SI. Recruitment and participation in clinical trials: socio-demographic, rural/urban, and health care access predictors. Cancer Detect Prev. 2006;30(1):24-33.
22. Robinson SB, Ashley M, Haynes MA. Attitude of African-Americans regarding prostate cancer clinical trials. J Community Health. Apr 1996;21(2):77-87.
23. Coyne CA, Demian-Popescu C, Brown P. Rural cancer patients' perspectives on clinical trials: a qualitative study. J Cancer Educ. Fall 2004;19(3):165-169.
24. Brown DR, Fouad MN, Basen-Engquist K, Tortolero-Luna G. Recruitment and retention of minority women in cancer screening, prevention, and treatment trials. Annals of Epidemiology. 2000;10(8, Supplement 1):S13-S21.
25. Pinto HA, McCaskill-Stevens W, Wolfe P, Marcus AC. Physician perspectives on increasing minorities in cancer clinical trials: an Eastern Cooperative Oncology Group (ECOG) Initiative. Ann Epidemiol. Nov 2000;10(8 Suppl):S78-S84.
26. Advani AS, Atkeson B, Brown CL, et al. Barriers to the participation of African-American patients with cancer in clinical trials: a pilot study. Cancer. Mar 15 2003;97(6):1499-1506.
27. Outlaw FH, Bourjolly JN, Barg FK. A study on recruitment of black Americans into clinical trials through a cultural competence lens. Cancer Nurs. Dec 2000;23(6):444-451; quiz 451-442.
28. Hudson SV, Momperousse D, Leventhal H. Physician perspectives on cancer clinical trials and barriers to minority recruitment. Cancer Control. Nov 2005;12:S93-S96.
29. Giuliano AR, Mokuau N, Hughes C, et al. Participation of minorities in cancer research: The influence of structural, cultural, and linguistic factors. Annals of Epidemiology. 2000;10(8, Supplement 1):S22-S34.
30. Linden HM, Reisch LM, Hart A, Jr., et al. Attitudes toward participation in breast cancer randomized clinical trials in the African American community: a focus group study. Cancer Nurs. Jul-Aug 2007;30(4):261-269.
31. Shavers VL, Lynch CF, Burmeister LF. Racial differences in factors that influence the willingness to participate in medical research studies. Ann Epidemiol. May 2002;12(4):248-256.
32. George SL. Reducing patient eligibility criteria in cancer clinical trials. J Clin Oncol. Apr 1996;14(4):1364-1370.
33. Fuks A, Weijer C, Freedman B, Shapiro S, Skrutkowska M, Riaz A. A Study in contrasts: Eligibility criteria in a twenty-year sample of NSABP and POG clinical trials. Journal of Clinical Epidemiology. 1998;51(2):69-79.
34. McCabe MS, Varricchio CG, Padberg RM. Efforts to recruit the economically disadvantaged to national clinical trials. Semin Oncol Nurs. May 1994;10(2):123-129.
35. Elks ML. The right to participate in research studies. J Lab Clin Med. Aug 1993;122(2):130-136.
36. Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol. May 1 2005;23(13):3112-3124.
37. Swanson GM, Bailar JC, 3rd. Selection and description of cancer clinical trials participants--science or happenstance? Cancer. Sep 1 2002;95(5):950-959.
38. Wood CG, Wei SJ, Hampshire MK, Devine PA, Metz JM. The influence of race on the attitudes of radiation oncology patients towards clinical trial enrollment. Am J Clin Oncol. Dec 2006;29(6):593-599.
39. Fracasso PM, Walker MS, Mathews KJ, et al. Coaching intervention as a strategy for enhancing accrual to phase I/II clinical trials. Journal of Clinical Oncology. June 20 2007;2007 ASCO Annual Meeting Proceedings Part I. Vol 25:S6580.
40. Fouad MN, Partridge E, Green BL, et al. Minority recruitment in clinical trials: a conference at Tuskegee, researchers and the community. Ann Epidemiol. Nov 2000;10(8 Suppl):S35-S40.
41. Fouad MN, Partridge E, Wynn T, Green BL, Kohler C, Nagy S. Statewide Tuskegee Alliance for clinical trials. A community coalition to enhance minority participation in medical research. Cancer. Jan 1 2001;91(1 Suppl):237-241.
42. Lai GY, Gary TL, Tilburt J, et al. Effectiveness of strategies to recruit underrepresented populations into cancer clinical trials. Clin Trials. 2006;3(2):133-141.
43. Sorensen G, Emmons K, Hunt MK, et al. Model for incorporating social context in health behavior interventions: applications for cancer prevention for working-class, multiethnic populations. Prev Med. Oct 2003;37(3):188-197.
44. Emmons K. Behavioral and Social Science Contributions to the Health of Adults in the United States. In: Smedley BD, Syme SL, eds. Promoting Health: Intervention Strategies from Social and Behavioral Research. Washington DC: The National Academies Press; 2000:254-321.

No comments:

Post a Comment