Minorities, Women, and Clinical Cancer Research

Minorities, Women, and Clinical Cancer Research: The Charge, Promise, and Challenge SANDRA MILLON UNDERWOOD, PhD, RN, FAAN

Significant progress has been made since the war against cancer was launched. Discoveries in molecular medicine, genetics, and epidemiology have led to the recognition that certain cancers are potentially preventable and that elements of lifestyle, along with genetic, hormonal, and metabolic factors can be altered to reduce cancer risk. Advances in medical technology have led to the development of new imaging methods and computer technologies that can aid in efforts to detect, diagnosis, and treat cancer. Since the offensive against cancer was initiated, cancer treatments have become more powerful, more precise, less drastic, and safer. As a result, cancer incidence and mortality have begun to decline. Yet, while the nation boasts of the progress being achieved relative to cancer incidence and mortality, and federal research agencies retort that research applies to all populations, it is apparent that the declines do not translate to all populations in the United States. Clinical research is essential to cancer prevention and control. Within the oncology community, clinical cancer research trials are viewed as an efficient and economical way for patients to secure stateof-the-science medical care. Recognizing the need to improve access to state-of-the-science cancer treatment and control programs, minority and female participation in clinical cancer research trials has been encouraged. This recommendation is based on the belief that increased participation in welldesigned clinical cancer research trials adhering to strict protocols and quality controls will, not only help validate the application of research findings to minority and female populations, but also result in better patient outcomes. Born out of a commitment to social equity, justice, beneficence, and the desire to ensure that data relevant to cancer prevention and control are both valid and generalizable to populations across the United States, several programs of research aimed toward increasing the representation of women and minorities in clinical cancer research have been pursued by the National Cancer Institute. This issue of the Annals of Epidemiology Minorities, Women, and Clinical Cancer Research presents issues and challenges that face the research community and descriptions of effective models, strategies, and practices that may be used to increase the participation of minorities and women in clinical cancer research trials and facilitate the conduct of research directed toward reducing the cancer burden within the United States. Ann Epidemiol 2000;10:S3–S12.  2000 Elsevier Science Inc. All rights reserved. KEY WORDS:

Cancer, Clinical Trials, Minorities, Women, Research

INTRODUCTION On December 23, 1971, President Richard M. Nixon signed the National Cancer Act—the first law passed by any nation that made the conquest of cancer a national priority (see Text Box 1) (1). Considered by many as a declaration of war against cancer, the legislation charged the director of the National Cancer Institute (NCI) to “coordinate all the activities of the National Institutes of Health relating to cancer with the National Cancer Program” and “with the advice of the National Cancer Advisory Board, [to] plan and develop an expanded, intensified, and coordinated cancer

From the University of Wisconsin-Milwaukee (S.M.U.), School of Nursing, Milwaukee, WI. Address correspondence and reprints to: Sandra Millon Underwood, PhD, RN, FAAN, School of Nursing, University of Wisconsin-Milwaukee, 1921 East Hartford Avenue, 7th Floor Mailroom, Milwaukee, WI 53201.  2000 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

research program encompassing the programs of the NCI, related programs of other research institutions, and other Federal and non-Federal programs.” The directive given to the leaders in the scientific and medical community was to establish a national program that would advance the country’s efforts against cancer and, thereby, reduce the burden of cancer among Americans in the United States. The war was to be fought through the conduct and support of basic and applied research with respect to the biology, cause, diagnosis, prevention, treatment, and rehabilitation of cancer; support of training for research scientists, clinicians, and educators; communication of cancer information to the lay community; and the rapid translation of research findings into clinical practice. It was anticipated that the heightened efforts would result in reductions in cancer incidence, reductions in cancer mortality, increased life expectancy and improved quality of life for cancer survivors, and ultimately the cure and/or eradication of cancer. 1047-2797/00/$–see front matter PII S1047-2797(00)00200-3

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Selected Abbreviations and Acronyms NCI ⫽ National Cancer Institute SEER ⫽ Surveillance, Epidemiology, and End Results

Text Box 1. National Cancer Act (Public Law 92-218) National Cancer Act (1) Public Law 920218 Purpose of the National Cancer Institute Sec.410. [285] The general purpose of the National Cancer Institute is the conduct and support of research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients. National Cancer Program Sec.411. [285a] The National Cancer Program shall consist of (1) an expanded, intensified, and coordinated cancer research program encompassing the research programs conducted and supported by the Institute and the related research programs of the other national research institutes, including an expanded and intensified research program for the prevention of cancer caused by occupational or environmental exposure to carcinogens, and (2) the other programs and activities of the Institute. Cancer Control Programs Sec. 412. [285a-1] The Director of the Institute shall establish and support demonstration, education, and other programs for the detection, diagnosis, prevention, and treatment of cancer and for rehabilitation and counseling respecting cancer. Programs established and supported under this section shall include: (1) locally initiated education and demonstration programs (and regional networks of such program) to transmit research results and to disseminate information respecting(A) the detection, diagnosis, prevention, and treatment of cancer, (B) the continuing care of cancer patients and the families of cancer patients, and (C) rehabilitation and counseling respecting cancer to physicians and other health professionals who provide care to individuals who have cancer;

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(2) the demonstration of and the education of students of the health professions and health professions in(A) effective methods for the prevention and early detection of cancer and the identification of individuals with a high risk of developing cancer, and (B) improved methods of patient referral to appropriate centers for early diagnosis and treatment of cancer; and (3) the demonstration of new methods for the dissemination of information to the general public concerning the prevention, early detection, diagnosis, and treatment and control of cancer and information concerning unapproved and ineffective methods, drugs, and devices for the diagnosis prevention, treatment and control of cancer. Significant progress has been made since the war against cancer was launched. Thirty years ago, little was known about the origin or biologic nature of cancer. Cancer, the group of diseases characterized by the uncontrolled growth and abnormal development of cells that is often followed by unpredictable spread, was once believed to result from humoral, viral, chemical, hormonal, and/or hereditary causes (2–4). However, new knowledge relative to the regulation of the normal cell cycle; the recent discovery of two classes of genes, oncogenes, and tumor suppressor genes; and the role of endogenous and environmental exposures have broadened the understanding of the genesis of cancer. Cancer is now characterized as a disease of altered genes and altered genetic function. It is now known that these alterations are inherited or acquired as a result of chemical or physical changes or the effects of viruses that have the potential to cause aberrations in cellular growth and development and uncontrolled cellular proliferation (3–5). Since the offensive against cancer was initiated, biologic discoveries have led to the recognition that certain cancers are potentially preventable and that elements of lifestyle and culture, along with genetic, hormonal, and metabolic factors, can be altered to reduce cancer risk (4, 6–10). Advances in medical technology have led to the development of new imaging methods and computer technologies that can assist in the efforts to detect, diagnose, and treat cancer. Surgical interventions have become more precise and less drastic, radiation therapy has grown more powerful and safer, and chemotherapeutic agents are now being used in combinations that inflict greater damage on cancer cells while selectively sparing normal cells. As a result, more patients are afforded the chance to fight their disease with less radical or invasive surgical procedures and nonsurgical options that spare vital organs and limbs, control cancer-related pain,

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FIGURE 1.

cancer-related fatigue, and treatment side effects, and preserve their self-determination and personal dignity. As a consequence of targeted efforts in the area of cancer prevention, screening, diagnosis, and treatment, cancer incidence and mortality have begun to decline (Figures 1 and 2). Recent reports from the NCI, the American Cancer Society, and the Centers for Disease Control and Prevention indicate that the incidence and mortality rates for all cancers combined decreased during 1990–1996, reversing an almost 20year trend of increasing cancer incidence and cancer mortality (11–14). Data demonstrate that the refinement of surgical, pharmacologic, and radiotherapeutic treatments have

resulted in prolonged life expectancy for many cancer patients, while advances in the management of cancer pain and the management of the sequelae of cancer therapy have led to significant improvements in patient quality of life. However, in spite of these advances, cancer continues to pose a major health threat to the American public. As a result, victory against cancer cannot yet be declared. THE UNEQUAL BURDEN Cancer is known to have an impact on all population groups. According to recent estimates, approximately 1.22 million

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FIGURE 2.

new cases of invasive carcinoma and more than 1 million cases of basal and squamous cell cancer of the skin or carcinoma in sites other than the urinary bladder, will be diagnosed in the year 2000. In addition, it is expected that the disease will kill approximately 552,200 people in the United States during this same year (11, 12). Yet, while the Nation boasts of the progress being achieved relative to cancer incidence and mortality, it is apparent that the declines do not affect all populations in the United States (11–18). Data demonstrate that all too often the major minority populations in the United States, African Americans, Hispanic Americans, Native Americans, Alaska Natives, Native Hawaiians, Asians and Pacific Islanders, bear a disproportionate share of the Nation’s cancer burden. Cancer incidence, mortality, and survival are known to vary widely between men and women of different racial/ethnic groups in the United States. However, when measures of incidence, mortality, length of survival, and quality of life are compared across these racial and ethnic groups, the differential effects of cancer and the magnitude of the differences are alarming. NCI’s Surveillance, Epidemiology, and End Results (SEER) Program is considered the most authoritative source of cancer statistics in the United States (14, 19). Data reported by the SEER Program demonstrate that cancer

incidence and mortality rates vary considerably between racial and ethnic groups in the United States (11–18) (Tables 1 and 2). A review of data reflecting 1988–1992 trends in cancer incidence by site, gender, race, and ethnicity demonstrate that the prostate, esophageal, oral, and lung cancer rates among African-American men, stomach cancer rates among Korean men, liver cancer rates among Vietnamese men, kidney cancer among Native-American men, and colorectal cancer rates among Alaska Native men are higher than those for any other racial or ethnic group in the United States (16). Vietnamese women are noted to have the highest incidence rates of stomach cancer (25.8 per 100,000) and cervical cancer (43.0 per 100,000). Alaska Native women are noted to have the highest incidence of colorectal cancer (67.4 per 100,000) and lung cancer (50.6 per 100,000). Although Hawaiian women are noted to have the highest incidence of cancer of the uterine corpus (23.9 per 100,000), ovarian cancer rates are noted to be the highest among NativeAmerican women (17.5 per 100,000). Data collected and reported by the SEER Program indicate that between 1988 and 1992 the cervical, stomach, thyroid, liver, and intrahepatic bile duct cancer mortality rates among Asian/Pacific Islanders, gallbladder cancer mortality rates among Hispanics, and prostate, breast (female), lung (male), colorectal, corpus uterus

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TABLE 1. SEER cancer incidence ratesa 1990–1996 by site, sex, and race ethnicity

All Races Male Female White Male Female African American Male Female Asian/Pacific Islander Male Female American Indian Male Female Hispanic Male Female

All sites

Lung and bronchus

Female breast

Prostate

Colon and rectum

482.8 342.9

74.5 41.7

— 109.1

151.9 —

53.4 37.3

480.2 361.6

73.1 43.3

— 113.2

147.3 —

53.2 36.8

598.0 335.6

112.3 46.2

— 99.3

222.9 —

58.1 44.9

325.5 244.9

52.4 22.5

— 72.6

81.5 —

47.5 31.4

177.8 136.8

25.3 13.5

— 33.9

46.5 —

21.5 12.4

326.9 243.2

38.8 19.6

— 69.4

102.8 —

35.7

24.0

Source: Ries LAG, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK, eds. SEER Cancer Statistics Review, 1973–1996. National Cancer Institute. Bethesda, MD, 1999. a Rates are per 100,000 population and age-adjusted to the 1970 U.S. population. SEER incidence data are from the 11 SEER areas. Hispanic is not mutually exclusive from whites, African Americans, Asian/Pacific Islanders, and Native Americans.

and uterus, oral, pancreatic, laryngeal, esophageal cancer and multiple myeloma mortality rates among African Americans are higher than those of any other racial/and or ethnic group in the United States (16). Data reporting 1990–1996 trends in cancer incidence and mortality indicate that among the major ethnic groups in the United States, African Americans have the highest overall risk of developing cancer (442.9 cancer per 100,000) and the greatest overall risk of dying from cancer (223.4 per 100,000) (14). Among men, overall cancer incidence rates are highest among African Americans (598.0 per 100,000) and lowest among Native-American men (177.8 per 100,000). Although the differences among women are less pronounced, overall cancer incidence is noted to be highest among non-Hispanic white women (361.6 per 100,000) and lowest among Native American women (136.8 per 100,000). Measures of 5-year relative cancer survival are used by NCI’s SEER Program to estimate the proportion of people in a given population who are alive after the diagnosis of cancer. As with the indices of cancer incidence and cancer mortality, considerable variation is noted in the 5-year relative cancer survival rates between minority and nonminority groups in the United States. According to the most recent SEER report, between 1989 and 1995, 5-year relative cancer survival for all sites and all races of people combined throughout the United States was reported to be 59%. However, while the 5-year relative cancer survival rate was 61% for whites, the survival rate was 48% among African Americans (Table 3).

Quality of life for cancer survivors is most often measured in terms of physical side effects, which may be both general and the result of treatment; functional status, both personal and social; psychological morbidity, expressed in both distress and depression; and coping and/or satisfaction in work or social relationships (20). Breakthroughs in cancer treatment and the management of cancer pain, fatigue, and the side effects of cancer therapy have led to improvements in the quality of life for many cancer patients (5, 9, 20–26). These improvements offer cancer patients relief from discomforts that are often associated with cancer and its treatment that were unattainable decades ago. However, many of these breakthroughs and improvements have not been translated into practice among cancer survivors of different racial/ethnic groups in the United States. Research demonstrates that throughout the United States, there are disparate variations in the delivery of cancer care to minority cancer patients (18, 26–32). Although pain is common to the cancer experience, it has been noted that it is often inadequately treated among minority cancer patients (33–35).

IMPROVING CANCER OUTCOMES: THE CHALLENGE There is no conclusive evidence to support any single explanation for the differential cancer burden among racial and ethnic population groups within the United States. It has been suggested that the trends in cancer incidence have

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TABLE 2. SEER cancer mortality ratesa 1990–1996 by site, sex, and race/ethnicity, United States

All Races Male Female White Male Female African American Male Female Asian/Pacific Islander Male Female American Indian Male Female Hispanic Male Female

All sites

Lung and bronchus

Female breast

Prostate

Colon and rectum

215.1 141.2

71.9 33.2

— 25.9

25.9 —

21.9 14.9

208.8 141.2

70.1 33.8

— 25.7

23.7 —

21.5 14.5

308.8 168.1

100.8 32.8

— 31.4

54.8 —

27.8 20.0

129.2 83.5

34.9 14.9

— 11.4

10.7 —

13.4 9.0

123.3 90.2

40.5 19.8

— 12.3

14.3 —

11.0 8.9

131.8 86.3

32.0 11.0

— 15.3

16.7 —

13.2 8.4

Source: Ries LAG, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK, eds. SEER Cancer Statistics Review, 1973–1996. National Cancer Institute. Bethesda, MD, 1999. a Rates are per 100,000 population and age-adjusted to the 1970 U.S. population. SEER incidence data are from the 11 SEER areas. Hispanic is not mutually exclusive from whites, African Americans, Asian/Pacific Islanders, and Native Americans.

arisen from myriad biological, hereditary, behavioral, and environmental factors (15, 18, 36–41). The trends in cancer mortality and survival are believed to be attributable to variations in cancer incidence, the stage of the cancer at the time of first treatment, and the standard of care administered. The trends relative to the quality of life experienced and expressed by cancer survivors are presumed to be associated with access to and utilization of state-of-the-art resources for cancer care. Gaining a better understanding of the factors that led to variations in cancer biology, incidence, mortality, survival, and quality of life among racial/ethnic population groups in the United States is paramount to accomplishing the goals of the National Cancer Program. The same is true relative to gaining a better understanding of racial, social,

and cultural factors that correlate with these differences, given that race, in the biological sense, may not be the cause (42–45). Although the NCI has long encouraged appropriate representation in clinical research, even with the imposition of the National Institutes of Health Revitalization Act (PL 103-43) and the development of guidelines on the inclusion of minorities and women in clinical research, often minorities and women are less than adequately represented in cancer research efforts (see Text Box 2) (46–47). Text Box 2. NIH Revitalization Act of 1993 (46) The NIH Revitalization Act of 1993, Public Law 103-43, signed by the President on June 10, 1993, directed the NIH to establish guidelines for

TABLE 3. SEER 5-year relative cancer survival ratesa 1974–1995 by site and race/ethnicity White Site All Sites Breast (Female) Lung and Bronchus Prostate Colon Rectum

African American

All Races

1974–1976

1980–1982

1989–1995

1974–1976

1980–1982

1989–1995

1974–1976

1980–1982

1989–1995

50 75 12 68 51 49

52 77 13 74 56 53

61 86 14 93 62 60

39 63 11 58 46 42

40 66 12 65 49 38

48 71 11 84 52 51

49 75 12 67 50 48

51 76 13 73 55 52

59 85 14 92 62 59

Source: Ries LAG, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK, eds. SEER Cancer Statistics Review, 1973–1996. National Cancer Institute. Bethesda, MD, 1999. a Survival data are age-adjusted for normal life expectancy and are based on followup of patients through 1996. SEER survival data are from the 11 SEER areas.

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the inclusion of women and minorities in clinical research. The Act required that the guidance include guidelines regarding(A) the circumstances under which the inclusion of women and minorities as subjects in projects of clinical research is inappropriate; (B) the manner in which clinical trials are required to be designed and carried out; and (C) the operation of outreach programs. NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research Required by the 1993 NIH Revitalization Act (47) It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification establishes to the satisfaction of the relevant Institute/Center Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances may be made by the Director, NIH, upon the recommendation of an Institute/Center Director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research. All NIH-supported biomedical and behavioral research involving human subjects is defined as clinical research. This policy applies to research subjects of all ages. NIH funding components will not award any grant, cooperative agreement or contract or support any intramural project to be conducted or funded in Fiscal Year 1995 and thereafter which does not comply with this policy. Clinical research is essential to cancer prevention and control. Clinical cancer research trials offer patients access to the most advanced and effective treatment options available in a research context. Within the oncology community, clinical cancer research trials are viewed as an efficient and economical way for patients to secure state-of-the-science therapy and medical care. Recognizing the need to improve access to state-of-the-science cancer treatment and control programs, the participation of minorities and women in clinical cancer research trials has been encouraged. This recommendation is based on the belief that increased participation in well-designed clinical cancer research trials that adhere to strict protocols and quality controls will not only

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help validate the application of research findings to minority and female population groups, but also result in better patient outcomes (5, 47–52). With this premise in mind, multiple studies specifically targeted to minority populations and studies targeted to issues, tumor types, or problems that differentially affect minority populations have been proposed. The same is true regarding the design of studies that specifically target women, and studies that aim to address cancer in women. Recipients of federally funded clinical research grants and cooperative agreements are required to include representation of minority groups and women in their study populations (46, 47, 53). Data reported by NCI-sponsored Cooperative Groups and the Community Clinical Oncology Program demonstrate that minorities have been adequately represented in cancer treatment trials relative to their cancer incidence (48–50, 52). However, reports indicate that they are often underrepresented in cancer prevention and control trials relative to their proportion in the U.S. population. Accrual of minorities into investigator-initiated clinical trials has not been similarly tracked and reported. The same is noted in reports that reflect accrual of women in clinical cancer research studies. As a result, the overall representation of minorities and women in NCI-sponsored trials remains unknown.

IMPROVE THE REPRESENTATION OF MINORITIES, WOMEN, AND CLINICAL CANCER RESEARCH: THE CHARGE Numerous reports suggest that, despite Federal policies and guidelines, the customary research subject is a white male. Many factors are known to hinder the participation of minorities and women in clinical research studies (54–70). For years, stereotyped as “difficult to reach,” “noncompliant,” “unreliable,” and “unwilling,” minorities have not been routinely included in trials or they have been systematically excluded by trialists from many clinical research studies of diseases, disorders, and conditions that affect them. Historical, educational, cultural, linguistic, economic, geographic, and social barriers have caused many to be fearful, wary, unwilling, and/or unable to participate in clinical research studies. Concerns expressed by health care providers about the methods, ethics, and costs of clinical research have led an untold number of providers to directly or indirectly discourage minority patient/client participation in research studies and clinical trials. Concerns about sample homogeneity and fetal teratogenicity have led many researchers to exclude women from participation in clinical research. As a result, to date many hypotheses related to the biology, prevention, diagnosis, detection, and treatment of cancer remain untested, and many research questions remain unanswered.

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Born out of a commitment to social equity, justice, beneficence, and the desire to ensure that data relevant to cancer prevention and control are both valid and generalizable to populations across the United States, several programs of research support were established by the NCI. In December 1995, the Women and Minority Recruitment: Small Grant Program was announced (RFA: CA-96-03) (71). The Early Detection Branch of NCI’s Division of Cancer Prevention and Control invited investigator-initiated small grant program applications to perform pilot studies, test new ideas, and/or gather information that would lead to the development of effective models and strategies to improve the participation of women and minority groups as subjects in Phase III cancer prevention and screening research. In January 1996, the Women and Minority Recruitment: Intervention Testing RFA was announced (RFA: CA-96-04) (72). The Early Detection Branch of NCI’s Division of Cancer Prevention and Control invited investigator-initiated grant applications for research to develop, implement, and test well-designed, hypothesis-based interventions aimed toward improving the participation of women and minority groups as subjects in Phase III cancer prevention and screening trials. In May 1996, the Cancer Training Branch of NCI’s Office of the Deputy Director for Extramural Sciences published an RFA for Regional Conferences on Recruitment and Retention of Minority Participants in Cancer Research (RFA: CA-96-015) (50). Applications were sought for the support of regional conferences, which presented strategies that would aid clinical cancer investigators in recruiting and retaining minority participants in clinical cancer research and promote collaborations among clinical investigators and the minority community. This issue of the Annals of Epidemiology highlights observations from NCI’s Women and Minority Recruitment: Small Grant Program, the Women and Minority Recruitment: Intervention Testing Program, the Regional Conferences on Recruitment and Retention of Minority Participants in Cancer Research, and several other NCI-sponsored efforts. Throughout the monograph, selected discoveries, historical events, and legislative milestones that have affected the health status of minorities, women, and clinical cancer research are chronicled; data that reflect issues, trends, and challenges relevant to minorities, women, and clinical cancer research are presented; perspectives of providers and researchers are described; structural, cultural, and linguistic factors affecting the participation of minorities in cancer research are identified; the experiences of minority populations in ongoing clinical cancer research studies are detailed; strategies for enhancing the participation of minorities, women, and clinical cancer research studies are described; recommendations to the scientific community for future research are proposed; and resources that could be used to strengthen collaborative relationships among policymakers,

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the health care system, health care providers, cancer investigators, and the community are highlighted. It is hoped that each of these important items will be considered and used by the scientific community to improve the participation of minorities and women in clinical cancer research.

REFERENCES 1. National Cancer Act. Public Law 92-218. 2. National Cancer Institute, National Institutes of Health. The dread disease. Bethesda, MD, 1998; http://rex.nci.hih.gov. 3. National Cancer Institute, National Institutes of Health. Closing in on Cancer: Solving a 5000 Year Old mystery. Bethesda, MD, 1998; NIH publication No. 98-2955. 4. National Cancer Institute, National Institutes of Health. NCI’s Research Programs: Pursuing the Central Questions of Cancer Research. Bethesda, MD, 1999. 5. National Cancer Institute, National Institutes of Health. The Nation’s investment in cancer research. Bethesda, MD, 1998; NIH publication no. 98-4373. 6. National Cancer Institute. Measures of progress against cancer: Cancer prevention. Bethesda, MD, 1993. 7. Greenwald P, Kramer BS, Weed DL, eds. Cancer Prevention and Control. New York: Marcel Dekker; 1995. 8. National Cancer Institute, National Institutes of Health. Measures of Progress Against Cancer: Advances in Early Detection. Bethesda, MD, 1993. 9. National Cancer Institute, National Institutes of Health. Measures of Progress Against Cancer: Cancer Control. Bethesda, MD, 1993. 10. President’s Cancer Panel. Report of the Chairman. Bethesda, MD, 1995; NIH publication no. 96-3179. 11. American Cancer Society. Cancer Facts and Figures, 2000. Atlanta, GA: 2000. 12. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. Ca Cancer J Clin. 2000;50:7–23. 13. Ries, LAG, Wingo, PA, Miller BA, Howe, HL, Weir, HK, Rosenberg, HM, Vernon, SW, Cronin, K, Edwards BK. (2000). The Annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer. Cancer. 88 (10), 2398–2424. 14. Ries LAG, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK, eds. SEER Cancer Statistics Review, 1973–1996. Bethesda, MD: National Cancer Institute, 1999. 15. American Cancer Society. Racial and ethnic patterns: Cancer facts and figures, 1997. Atlanta, GA, 1997; publication no. 8620-R. 16. Miller BA, Kolonel LN, Bernstein L, Young Jr. JL, Swanson GM, West D, et al., eds. Racial/ethnic patterns of cancer in the United States, 1988–1992. Bethesda, MD: National Cancer Institute, 1996; NIH publication no. 96-4104. 17. National Center for Health Statistics. Health, United States, 1998 with socioeconomic status and health chartbook. Hyattsville, MD: US Department of Health and Human Services, 1998; DHHS publication no. 98-1232. 18. American Cancer Society. American Cancer Society facts and figures for African Americans, 1998–1999. Atlanta, GA, 1998; publication no. 8614.98-R. 19. Swan J, Wingo P, Clive R, West D, Mill D, Hutchinson C, et al. Cancer surveillance in the US: Can we have a national system? Cancer. 1998;83:1282–1291. 20. Roukos DH. Current advances and changes in treatment strategy may

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improve survival and quality of life in patients with potentially curable gastric cancer. Ann Surg Oncol. 1999;6:46–56.

44. Cooper R. Ethnicity and disease prevention. Am J Human Biol. 1993; 5:387–398.

21. Cella D. Factors influencing quality of life in cancer patients: Anemia and fatigue. Semin Oncology. 1998;5:43–46.

45. National Cancer Institute, National Institutes of Health. Report of the President’s Cancer Panel: The meaning of race in science— considerations in cancer research. Bethesda, MD, 1997.

22. Terrell JE, Fisher SG, Wolf GT. Long-term quality of life after treatment of laryngeal cancer. The Veterans Affairs Laryngeal Cancer Study Group. Arch Otolaryngol Head Neck Surg. 1998;124:964–971. 23. Dorval M, Maunsell E, Deschenes L, Brisson J. Type of mastectomy and quality of life for long term breast carcinoma survivors. Cancer. 1998;83:2130–2138. 24. Cella D, Perteman A, Passik S, Jacobsen KP, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology. 1998;12: 369–377. 25. King C, Haberman M, Berry D, Bush N, Butler L, Dow K, et al. Quality of life and the cancer experience: The state of knowledge. Oncol Nurs Forum. 1996;24:27–41. 26. Jacox A, Carr DB, Payne R, et al. Management of cancer pain. Clinical practice guidelines. Rockville, MD: US Department of Health and Human Services, Public Health Services, 1994; AHCPR publication no. 94-0592. 27. Horner RD. Racial variation in cancer care: A case study of prostate cancer. Cancer Treat Res. 1998;97:99–114. 28. Polednak AP. Prostate cancer treatment in black and white men: The need to consider both stage at diagnosis and socioeconomic status. J Natl Med Assoc. 1998;90:101–104. 29. Klabunde CN, Potosky AL, Harlan LC, Kramer BS. Trends and black/ white differences in treatment for nonmetastatic prostate cancer. Med Care. 1998;36:1337–1348.

46. National Institutes of Health. Revitalization Act. Public Law 103-45. 47. US Department of Health and Human Services. NIH guidelines on the inclusion of women and minorities as subjects in clinical research. Fed Register. 1994;59:14508–14513. 48. Bleyer WA. Recruiting minorities into clinical trials: Toward a participant-friendly system. JNCI. 1996;88:377.V 49. Bleyer WA, Tejeda HA, Murphy SB, Brawley OW, Smith MA, Ungerleider RS. Equal participation of minority patients in US national pediatric cancer clinical trials. J Pediatr Hematol Oncol. 1997;19: 423–427. 50. Tejeda HA, Green SB, Trimble EL, Ford L, High JL, Ungerleider RS, et al. Representation of African Americans, Hispanics, and Whites in National Cancer Institute Treatment Trials. J Natl Cancer Inst. 1996;88:812–816. 51. Brawley OW, Tejeda H. Minority inclusion in clinical trails: issues and potential strategies. Monograph of the National Cancer Institute, 1995;17:55–57. 52. Kaluzny A, Brawley O, Garson-Angert D, Shaw J, Godley P, Warnecke R, et al. Assuring Access to state-of-the-art care for US minority populations: The first 2 years of the Minority-Based Community Clinical Oncology Program. JNCI. 1993;23:1945–1950. 53. LaRosa JH. Including women and minorities in clinical research. App Clin Trials. 1995;4:31–33.

30. Gaffin J. Opening doors, improving access to hospice and specialist palliative care services by member of the black and minority ethnic communities. Cancer. 1996;29:S51–53.

54. Corbie-Smith G. The continuing legacy of the Tuskegee Syphilis Study: Considerations for clinical investigation. Am J Med Sci. 1999;317:5–8.

31. Kagawa-Singer M. Socioeconomic and cultural influences on cancer care in women. Semin Oncol Nurs. 1995;11:109–119.

55. Freedman TG. Why don’t they come to Pike Street and ask us?: Black American women’s health concerns. Soc Sci Med. 1998;47: 941–947.

32. Ashing-Giwa KM, Ganz PA, Petersen L. Quality of life of AfricanAmerican and white long-term breast carcinoma survivors. Cancer. 1999;85:418–426.

56. El-Sadr W, Capps L. The Challenge of minority recruitment in clinical trials for AIDS. J Am Med Assoc. 1992;267:954–957.

33. Bernabel R, Gambassi GM, Lapane K, Landi F, Gatsonis C, Dunlop R, et al. Management of pain in elderly patients with cancer. J Am Med Assoc. 1998;279:1877–1882.

57. Hayunga EG, Pinn VW. Women and minorities in clinical research: Responding to concerns of the research community. App Clin Trials. 1996;5(11):59–64.

34. Cleeland CS, Gonin R, Baez L, Loehrer P, Pandya KJ. Pain and treatment of pain in minority patients with cancer. The Eastern Cooperative Oncology Group Minority Outpatient Pain Study. Ann Internal Med. 1997;127:813–816.

58. Thomas Jr CR, Pinto HA, Roach III M, Vaughn CB. Participation in clinical trials: Is state-of-the-art treatment for African American and other people of color. J Natl Med Assoc. 1994;86:177–182.

35. Yabroff KR, Linas BP, Schulman K. Evaluation of quality of life for diverse patient populations. Breast Cancer Res Treat. 1996;40:87–104.

59. Swanson GM, Ward AJ. Recruiting minorities into clinical trials: Toward a participant-friendly system. J Natl Cancer Inst. 1995;87: 1747–1759.

36. Alexander GA. Cancer control in special populations: African Americans, Native Americans, Hispanics, poor and underserved. In: Greenwald P, Kramer BS, Weed DL, eds. Cancer Prevention and Control. NY: Marcel Dekker; 1995.

60. McCabe MS, Varrichio CG, Padberg RM. Efforts to recruit the economically disadvantaged to national clinical trials. Semin Oncol Nurs. 1994;10:123–129.

37. Baquet CR, Hunter CP. Patterns in minorities and special populations. In: Greenwald P, Kramer BS, Weed DL, eds. Cancer Prevention and Control. NY: Marcel Dekker; 1995. 38. Guidry JJ, et al. Transportation as a barrier in cancer treatment. Cancer Practice. 1997;5:361–366.

61. Roberson NL. Clinical trial participation: Viewpoints from racial/ ethnic groups. Cancer. 1994;74:2687–2691. 62. McCarthy CR. Historical background of clinical trials involving women and minorities. Acad Med. 1994;69:695–698.

39. Guidry JJ, et al. Information sources and barriers to cancer treatment by racial/ethnic minority status of patients. J Cancer Edu. 1998;13:43–48.

63. Millon Underwood S, Sanders E, Davis M. Determinants of participation in state-of-the-art cancer prevention, early detection/screening, and treatment of trials among African Americans. Cancer Nurs. 1993;16:25–33.

40. Brenner PR. Issues of access in a diverse society. Hospital J. 1997;12: 9–16.

64. Altman K, Amato D, Wood W, Corson J, Suit H, Proppe K, et al. Selection bias in clinical trials. J Clin Oncol. 1985;3:1142–1147.

41. Horner RD. Racial variation in cancer care: A case study of prostate cancer. Cancer Treat Res. 1998;97:99–14.

65. Taylor KM, Margolese RG, Soskolne CL. Physician’s reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. New Engl J Med. 1984;310:1363–1367.

42. Freeman HP. The meaning of race in science: Considerations for cancer research. Cancer. 1998;82:219–225. 43. Liu ET. The uncoupling of race and cancer genetics. Cancer. 1998; 83:1765–1769.

66. Cassileth BR, Lusk EJ, Miller DS, Hurwitz S. Attitudes toward clinical trials among patients and the public. J Am Med Assoc. 1982;248: 968–970.

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67. Mouton CO, et al. Barriers to black women’s participation in cancer clinical trials. J Natl Med Assoc. 1997;89:721–727.

70. Caplan AL. Twenty years after: The legacy of the Tuskegee Syphilis Study. When evil intrudes. Hastings Center Rep. 1992;22:29–32.

68. Gamble VN. Under the shadow of Tuskegee: African Americans and health care. Am J Public Health. 1997;87:1773–1778.

71. Women and minority recruitment: Small Grant Program. RFA: CA96-03. NIH Guide, December 1995.

69. Harris Y, Gorelick PB, Samuels P, Bempong I. Why African Americans may not be participating in clinical trials. J Natl Med Assoc. 1996; 88:630–634.

72. Women and minority recruitment: Intervention testing. RFA: CA96-04. NIH Guide, January 26, 1996;25(1).