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Journal of Clinical Oncology, Vol 26, No 20 (July 10), 2008: pp. 3380-3386 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.6027 Analysis of Maryland Cancer Patient Participation in National Cancer Institute–Supported Cancer Treatment Clinical Trials
From the Department of Internal Medicine, Office of Policy and Planning, the University of Maryland Comprehensive Center for Health Disparities Research, Outreach, and Training; and Department of Family and Community Medicine, Center for Health Policy/Health Services Research, University of Maryland School of Medicine, Baltimore, MD Corresponding author: Claudia R. Baquet, MD, MPH, University of Maryland School of Medicine, 685 West Baltimore St, Suite 618, Baltimore, MD 21201; e-mail: cbaquet{at}som.umaryland.edu
Purpose We examined the relationship of sociodemographic factors, urban/rural residence, and county-level socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI) –sponsored cancer treatment clinical trials. Patients and Methods Data were analyzed for the period 1999 to 2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI's Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. Results For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. Conclusion Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved.
Factors contributing to cancer disparities are numerous and complex, including lower participation of racial/ethnic minority and underserved patients in clinical trials.1-4 Assuring diversity in clinical trials is essential to eliminating health disparities, because lower participation of racial/ethnic minority and underserved patients reduces the generalizability of therapeutic and drug development trials to these groups, thus impeding treatment and survival advances. Clinical trials have produced prevention, treatment, and outcome advances, and nowhere has this been more evident than for cancer treatment trials.3,5 Although trials are proven to contribute to cancer therapy and prevention advances, clinical trial participation for the general cancer patient population is low (5% to 9%).3,5 Despite federal legislation and regulatory efforts to improve accrual,6 African Americans, rural, and underserved patients with cancer continue to participate in cancer trials at even lower rates than the general population.1,2,4,7-10 Some contributing factors remain unclear, yet modifiable factors do contribute to disparities in clinical research and trial participation.2-5,7,8,10-17 Factors include lack of awareness of available trials by community physicians and patients; lack of community awareness of the role and potential benefits of research participation; historical concerns, including Tuskegee and more recent exploitive research; distrust of academic institutions; poor researcher communication skills; lack of cultural competence of research personnel; modifiable design barriers, including rigid and exclusionary eligibility criteria; and reimbursement for trial-associated costs. Although an extensive community cancer trial infrastructure exists in the National Cancer Institute's (NCI) Community Clinical Oncology program and Minority-Based–Community Clinical Oncology program, not all community oncology practices are eligible for inclusion because of small accrual and other factors. This includes the single oncologist practice that is part of the Maryland Best Practice.18 In Maryland, we have implemented data-driven, targeted community-based participatory programs to enhance accrual to trials. The University of Maryland School of Medicine (UMSOM) has an intensive, multilevel program to increase cancer trial accrual and availability in minority and rural underserved communities. Eastern Shore Cancer Research Network, a single community oncologist practice located on the Eastern Shore of Maryland, and UMSOM shared a National Best Practice award from the Secretary of the Department of Health and Human Services Committee on Science and Policy in September 2004.18 An earlier Maryland study reported that 11.1% of Marylanders reported being recruited to clinical trials; of those, 59.4% actually participated.4 This study characterizes participation of Maryland patients with cancer in NCI-sponsored therapeutic trials for the period 1999 to 2002 by key demographic, racial/ethnic, geography of residence (rural/urban), and county-level socioeconomic factors. The extent to which Maryland patients with cancer accrued onto NCI-sponsored treatment trials were representative of all Maryland patients with cancer was also examined.
Maryland Patients With Cancer Maryland geographic and demographic cancer burden was determined using cancer incidence data from the population-based Maryland Cancer Registry for all patients newly diagnosed with cancer from 1999 to 2002. Data were obtained on primary cancer site, 10-year age group, race (white, black, or other), sex, and jurisdiction of residence at diagnosis. Maryland jurisdictions, consisting of 23 counties and Baltimore City, were used for geographic analyses.
Cancer Treatment Clinical Trial Patients For each patient, data included zip code of residence, 10-year age group, sex, race/ethnicity, and payment method (private insurance, Medicare or Medicaid, military, or self-pay). In addition, patients were assigned to a specific jurisdiction based on zip code data from the Maryland Department of Planning.19 Data have been analyzed by zip code of residence, thus data on Maryland patients with cancer treated in Maryland- and non-Maryland–based institutions are included in the analyses.
County Level Socioeconomic and Demographic Data
Two methods were used to examine urban/rural composition of Maryland jurisdictions. The Beale classification system22 classified counties as (1) metropolitan area with
Health Care System–Level Variables
Analysis
Accrual onto NCI-sponsored treatment trials was also examined by several county-level socioeconomic and demographic variables. We estimated odds ratios (ORs) and 95% CIs using logistic regression and used generalized estimating equations to account for clustering of individuals within county.25 Accrual onto treatment trials was modeled as a function of county-level socioeconomic and demographic factors and health system–level characteristics of Maryland counties. Each demographic variable was categorized into quartiles. Continuous socioeconomic, demographic, or health system–level variables were placed in logistic regression models to assess linear trends. Statistically significant estimates from Wald
For 1999 to 2002, 2,240 Maryland patients with cancer were accrued onto NCI-sponsored treatment trials, representing an average accrual rate of 2.3% (data not shown). The percentage of Maryland patients with cancer accrued onto treatment trials increased from 1.9% in 1999 to 2.9% in 2002 (  2trend = 86.4; df = 1; P < .0001).
Accrual by Age Group
Accrual by Sex and Cancer Site Male patients (31.4%) and female patients (30.0%) were almost identical with regard to Maryland's cancer burden percentage for non–sex-specific cancer sites (Table 2). For these cancer sites, male patients were significantly more likely than female patients (46.8% v 21.8%; P < .0001) to be accrued onto treatment trials. However, for sex-specific tumors, the Maryland cancer burden for male patients was 32.3%, but only 21.6% of male patients participated in reproductive system neoplasms trials. For female patients, although the Maryland cancer burden was 33.6%, 53.7% participated in breast cancer treatment trials and 12.3% participated in reproductive neoplasm trials.
Accrual by Race/Ethnicity and Sex For 1999 to 2002, there were modest fluctuations in accrual for white patients; however, there was a significant decline in accrual of black patients (Table 3). Estimated annual decline in the percentage of black patients accrued onto treatment trials was approximately 8.9% per year (P < .05). The highest percentage of individuals accrued onto treatment trials was white female patients, followed by white male patients, black female patients, and black male patients. During the same period, the accrual of female patients was significantly higher than that of male patients (59.2% v 40.8%; P < .01). Within each racial/ethnic group, with the exception of American Indian or Alaska Native, a higher percentage of female patients were accrued than male patients. Overall, the racial distribution of patients enrolled onto trials was similar to the racial distribution of Maryland patients with cancer.
Accrual by Insurance Status Compared with the general Maryland population, a lower percentage of trial patients were uninsured (3.4% v 13.4%), were insured with Medicaid (3.2% v 6.5%), and had private insurance (65.4% v 77%; data not shown). Although no differences were observed in government coverage (ie, Medicare, Medicaid, and/or Military–Veterans' Administration) as a whole, a larger percentage of Maryland trial patients than the general population were covered by some form of Military–Veteran's Administration insurance (6.5% v 3.9%).
Accrual by Maryland Regions
Accrual by County-Level Sociodemographic and Health System Characteristics Logistic regression models suggest different accrual patterns for female patients and male patients (Table 5). For female patients, odds of accrual onto treatment trials was lower among women in the highest quartile of deprivation scores than among those in the lowest (OR = 0.45; 95% CI, 0.23 to 0.89). For both female and male patients, the trend of lower accrual onto trials with increasing deprivation scores was statistically significant (P < .001). Similarly, county social class was strongly associated with treatment trial accrual among women (OR = 2.29; 95% CI, 1.84 to 2.83 for the highest compared with the lowest quartiles) and men (OR = 1.57; 95% CI, 1.32 to 1.86). Accrual among female patients and male patients increased as the county social class score increased (P = .011 for female patients; P  .001 for male patients). The adjusted odds of accrual decreased with each 2% increase in counties' nonwhite population composition among females and 1% among males (P = .001).
This study comprehensively examined participation of Maryland patients with cancer in NCI-sponsored CTCG treatment trials. Our findings show that, for the period from 1999 to 2002, Maryland patients with cancer enrolled onto treatment trials at a higher rate included pediatric and adolescent age groups, male patients for non–sex-specific tumors and female patients for sex-specific tumors, those with private health insurance, and those residing in the Maryland National Capitol (specifically Montgomery County) and parts of the Baltimore Metro (especially Baltimore and Anne Arundel Counties) regions. In addition, there were different patterns of accrual for female and male patients on county level socioeconomic factors. This study was modeled on the report by Sateren et al3 that examined accrual onto NCI-sponsored treatment trials nationally for a 12-month period. Our study differs from that of Sateren et al in several key ways. We present data on accrued patients, cancer rates, and accrual trends from one state for a 4-year period and provide more detailed measures of material deprivation and rural residence. Although accrual data were presented for all racial/ethnic groups, because of low numbers of patients other than black or white, analyses were not possible for these groups. Additionally, although cancer sites (colorectal, lung, leukemia, and lymphoma) were selected to make appropriate comparisons with the national analysis, additional cancers of significance to Maryland residents (ie, female breast and male reproductive [prostate included]) were also examined. Although requested from NCI, accrual data on race by age group were not obtained; therefore, such analyses were not possible in this report. From 1999 to 2002, there was an increase in accrual of Maryland patients with cancer to NCI-sponsored treatment trials. Moreover, the overall accrual rate of Maryland patients with cancer to NCI-sponsored treatment trials was comparable to that of national CTCG accrual rates.3 As reported elsewhere,3 accrual was highest for pediatric patients with cancer and lowest among adults age 60 years and older. Low accrual of adults age 60 years and older is disconcerting, as they are at high risk for a cancer diagnosis and are insured through Medicare, which instituted a coverage policy for beneficiary trial participation in 2000 and amended it in July 2007. Despite comparable cancer burden for some cancers, there were significant sex differences in accrual for Maryland patients with cancer. Male and female patients had relatively similar rates for colorectal cancer, leukemia, and lymphoma; however, male patients were significantly more likely to be enrolled onto treatment trials. On the other hand, despite comparable sex-specific cancer rates (reproductive cancers for male patients and breast cancer for female patients), there was significantly higher accrual of female patients to sex-specific cancer treatment trials. The majority of Maryland's accrual data by race is for black and white patients. Although modest fluctuations in accrual for white patients occurred during this period, decline in accrual of black patients, who experience significant cancer rates, should be noted and is similar to that reported nationally.3 Decline in enrollment of African Americans warrants immediate study and may be due to factors such as distrust, lack of available trials, limited information, age, and exclusionary criteria for comorbidity (also see Murthy et al2 and Baquet et al4). Lack of insurance coverage and reimbursement for trials is a real and perceived barrier to clinical trial accrual.26 Overall, the majority of Maryland patients with cancer in treatment trials were covered by health insurance. Similar to national data,3 the majority of Maryland trial patients were privately insured. However, unlike the national data,3 a lower proportion of Maryland trial patients were covered by Medicaid, a higher proportion were government insured, and the percentage of Medicare patients accrued on trials was similar to the percentage of individuals covered by Medicare in the state. Clinical trial participation cost is a concern. The majority (60%) of patients do not take part in clinical trials because of fear of having their insurance denied,26,27 and oncologists have reported denial for routine care costs as an obstacle to enrollment.26,28 In 1998 and 1999, Maryland passed state health insurance mandates into law on coverage of trial-associated clinical costs.26,27 Although the Maryland law mandates coverage for trial-associated costs, restrictions in application of this law make this benefit, and other mandated health benefits, available to only 25% of the insured.27 There were substantial differences in trials accrual for Maryland regions, with higher observed than expected accrual in the National Capitol region (comprised of Montgomery and Prince George's Counties), equivalent accrual in the rural Eastern Shore, and lower than expected accrual in rural Northwest and Southern Maryland regions. Although viewed as a wealthy county, Montgomery County has pockets of underserved communities and is the location of the NIH and its Clinical Center, which may explain higher than expected trial accrual. Prince George's County, adjacent to Montgomery County and having a large African American community, had lower than expected accrual, which may be an artificially low rate owing to the proximity of other centers. All patients were enrolled in cancer treatment trials at institutions outside of the county. Unlike the lower than expected accrual observed in the rural Northwest and Southern Maryland regions, the Eastern Shore observed-versus-expected accrual was equivalent. This could be explained by the intensive, multilevel programs and partnership with Eastern Shore Cancer Research Network and UMSOM that includes concentrated education, trial infrastructure, and outreach to the public, local physicians, and nurses to increase cancer trial accrual and availability in the rural Eastern Shore.18 These findings present a compelling case for future research on declining trends in accrual of black patients onto treatment trials, differential accrual by sex for comparable prevalence of specific cancer burden, differential accrual by sex within racial/ethnic groups, and lower than expected accrual rates in Prince George's County and rural Northwestern and Southern Maryland regions. There is a need to enhance targeted educational and outreach efforts to communities and community-based health professionals to increase trial availability and to foster trial participation, accrual, and retention. Educational efforts should inform minorities and community physicians on design, regulatory and reporting aspects on clinical trials, and foster public trust, health literacy, and community understanding of the importance of representative numbers in clinical research, institutional review boards, informed consent, and potential for research benefits. This study has important features. It extends existing research by Sateren et al3 in several key areas. In the absence of individual socioeconomic data, study limitations include use of demographic data for county population and not for individual Maryland patients with cancer. Therefore, it is difficult to determine the independent effect of geography of residence and individual-level racial and socioeconomic differences on treatment trial accrual. Observed multivariable logistic regression results may be due to uncontrolled confounding by individual social and economic resources, as well as barriers to participation, which may bias results in an unpredictable manner. We examined accrual of Maryland patients with cancer to NCI-sponsored treatment trials from CTCGs, thus individuals participating in prevention or industry trials or investigator-initiated treatment trials supported by NCI cannot be commented on, and results cannot be extended to the general population of patients participating in all clinical trials. This examination of participation of Maryland patients with cancer in NCI-sponsored treatment trials has identified significant disparities in trial accrual among Maryland patients with cancer. Findings provide a compelling argument for intensive, ongoing efforts to understand and address barriers to clinical research and trial participation in Maryland and for tailored and targeted educational efforts to improve accrual.
The author(s) indicated no potential conflicts of interest.
Conception and design: Claudia R. Baquet Financial support: Claudia R. Baquet Administrative support: Claudia R. Baquet Provision of study materials or patients: Claudia R. Baquet Data analysis and interpretation: Claudia R. Baquet, Gary L. Ellison, Shiraz I. Mishra Manuscript writing: Claudia R. Baquet, Gary L. Ellison, Shiraz I. Mishra Final approval of manuscript: Claudia R. Baquet
Supported by grants from the National Center for Minority Health and Health Disparities (Grant No. P60MD000532) and National Cancer Institute (Grants No. U01CA114650 and 5U01CA86249). The National Cancer Institute Cancer Therapy Evaluation Program provided patient data based on a freedom of information request by C.R.B. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. McCaskill-Stevens W, Pinto H, Marcus AC, et al: Recruiting minority cancer patients into cancer clinical trials: A pilot project involving the Eastern Cooperative Oncology Group and the National Medical Association. J Clin Oncol 17:1029-1039, 1999 2. Murthy VH, Krumholz HM, Gross CP: Participation in cancer clinical trials: Race-, sex-, and age-based disparities. JAMA 291:2720-2726, 2004 3. 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 20:2109-2117, 2002 4. Baquet CR, Commiskey P, Daniel Mullins C, et al: Recruitment and participation in clinical trials: Socio-demographic, rural/urban, and health care access predictors. Cancer Detect Prev 30:24-33, 2006[CrossRef][Medline] 5. Comis RL, Miller JD, Aldige CR, et al: Public attitudes toward participation in cancer clinical trials. J Clin Oncol 21:830-835, 2003 6. 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 trialists. Control Clin Trials 16:277-285, 1995[CrossRef][Medline] 7. Brown DR, Fouad MN, Basen-Engquist K, et al: Recruitment and retention of minority women in cancer screening, prevention, and treatment trials. Ann Epidemiol 10:S13-S21, 2000 (suppl)[CrossRef][Medline] 8. Harris Y, Gorelick PB, Samuels P, et al: Why African Americans may not be participating in clinical trials. J Natl Med Assoc 88:630-634, 1996[Medline] 9. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061-2067, 1999 10. Lewis JH, Kilgore ML, Goldman DP, et al: Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21:1383-1389, 2003 11. Ellis PM, Butow PN, Tattersall MH, et al: Randomized clinical trials in oncology: Understanding and attitudes predict willingness to participate. J Clin Oncol 19:3554-3561, 2001 12. Giuliano AR, Mokuau N, Hughes C, et al: Participation of minorities in cancer research: The influence of structural, cultural, and linguistic factors. Ann Epidemiol 10:S22-S34, 2000 (suppl)[CrossRef][Medline] 13. Mandelblatt JS, Yabroff KR, Kerner JF: Equitable access to cancer services: A review of barriers to quality care. Cancer 86:2378-2390, 1999[CrossRef][Medline] 14. Mouton CP, Harris S, Rovi S, et al: Barriers to black women's participation in cancer clinical trials. J Natl Med Assoc 89:721-727, 1997[Medline] 15. Shavers VL, Lynch CF, Burmeister LF: Racial differences in factors that influence the willingness to participate in medical research studies. Ann Epidemiol 12:248-256, 2002[CrossRef][Medline] 16. Shavers-Hornaday VL, Lynch CF, Burmeister LF, et al: Why are African Americans under-represented in medical research studies? Impediments to participation. Ethn Health 2:31-45, 1997[Medline] 17. Zhu K, Hunter S, Bernard LJ, et al: Recruiting elderly African-American women in cancer prevention and control studies: A multifaceted approach and its effectiveness. J Natl Med Assoc 92:169-175, 2000[Medline] 18. United States Department of Health and Human Services: A model for increasing availability of community-based cancer clinical trials in rural eastern shore Maryland. 2004. http://www.phs.os.dhhs.gov/ophs/BestPractice/MD_cancer.htm/ 19. Maryland Department of Planning: Planning Data Services. http://www.mdp.state.md.us/ 20. United States Census. 2000. http://www.census.gov/ 21. Klassen AC, Curriero FC, Hong JH, et al: The role of area-level influences on prostate cancer grade and stage at diagnosis. Prev Med 39:441-448, 2004[CrossRef][Medline] 22. United States Department of Agriculture: Measuring Reality: Rural-Urban Continuum Codes. April 28, 2004 update. http://www.ers.usda.gov/briefing/rurality/RuralUrbCon/ 23. United States Department of Agriculture: Data Sets: Urban Influence Codes. http://www.ers.usda.gov/Data/UrbanInfluenceCodes 24. American College of Surgeons: Commission on Cancer. http://www.facs.org/cancerprogram/ 25. Stokes ME, Davis CS, Koch GG: Categorical Data Analysis Using the SAS System (ed 2). Cary, NC, SAS Institute Inc, 2000 26. Baquet CR: The role of state legislation and policy in addressing disparities in clinical trials. http://www.bcm.edu/edict/PDF/State_Legislation.pdf 27. American Cancer Society: Clinical Trials: State Laws Regarding Insurance Coverage. http://www.cancer.org/docroot/ETO/content/ETO_6_2x_State_Laws_Regarding_Clinical_Trials.asp 28. American Society of Clinical Oncology: Coverage of Routine Patient Care Costs in Clinical Trials: Position Statement (approved by the ASCO Board of Directors in 2005). http://www.asco.org/ASCO/Legislative+%26+Regulatory Submitted September 25, 2007; accepted March 28, 2008.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
1 million population, (2) metropolitan area of less than 250,000 population, and (3) nonmetropolitan area with urban population of 
