Session II. Minority Investigators in Clinical Trials? How Important Are They?

Discussion Leaders: Clemente Diaz, M.D., Professor and Chairman, Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico, and Michele K. Evans, M.D., Deputy Scientific Director, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland

Dr. Clemente Diaz presented the Hispanic perspective on the importance of minority investigators in clinical trials. The underrepresentation of minorities in clinical trials resulted in a 1993 congressional mandate that led to the NIH policy on inclusion of women and minorities in clinical research. There is a need to understand how history, attitudes, cultural beliefs, social issues, and investigative behavior actually affect the enrollment of minorities in clinical trials. The NIH policy resulted from a response to ethical principles of social justice and the need to balance research burdens and research opportunities and benefits across society.

Minority Researchers: How Are They Effective?

Dr. Diaz stated that minority researchers are effective because they are part of the community and, therefore, function as access points for minority populations to participate in research. Sometimes minority researchers work in settings that are isolated in terms of minority representation; therefore, they are key to accessing research for minority populations. Minority researchers offer a cultural empathy, which acts as a bridge to minority participants. Minority researchers also know the communities that are advocates for minority populations and have negotiated good relationships with organizations that offer access points to these minority populations. Strong bonds with community-based organizations can lead to partnerships to enhance not only enrollment but also retention and involvement. In addition, by role modeling and mentoring, minority researchers foster and promote increasing numbers of minority researchers for the future. Minority students may be reluctant to choose research as a profession because of the lack of financial incentives. Therefore, when minority researchers act as mentors, they become instrumental in helping to increase the number of primary investigators.

Hispanics as Participants

Dr. Diaz focused on the heterogeneity of the Hispanic population. Hispanics comprise Mexicans, Puerto Ricans, Cubans, South and Central Americans, and Spaniards. Although Hispanics share certain values and a language, there are significant differences among them. Researchers must recognize these differences in order to successfully enroll Hispanics in clinical trials. In many instances, issues of trust, language, religion, and cultural beliefs affect how research is perceived by Hispanics. This population must perceive the benefits and value of research, especially regarding high-prevalence conditions that indicate health disparities, such as HIV/AIDS, tuberculosis, breast and cervical cancers, cardiovascular diseases, asthma, hypertension, and diabetes. For example, asthma is extremely prevalent in Puerto Ricans, and diabetes is an increasing problem for Hispanics. Because Hispanics perceive these issues as relevant, they will be interested in participating in clinical trials in these areas.

Health issues and disparities in Hispanics raise some political issues. Language and acculturation are important for Hispanics, and the issues are very different for the first generation, second generation, etc. Likewise, gender role issues are important; men and women have different health care behaviors. Hispanic men tend to disregard as a waste of time preventive health care behaviors such as yearly physical examinations. Hispanic women postpone preventive care because of their role as caregivers for family members and children.

In addition, decisionmaking in the family is important. For Hispanics, that fact translates into difficulties in getting informed consent; Hispanic people need time to discuss informed consent with family members. In general, Hispanics have less access to health insurance, which limits their access to preventive health services. They also lack access to public health education materials, for example, vaccination information.

There are also differences in trust, reactions to medication, and perception of pain; therefore, an individual approach is often necessary. Questions will arise regarding access to urgent care and to emergency room services, perception of pain and threshold of pain, and recognizing and reporting adverse events--all critical issues for clinical trials.

Promoting the Inclusion of Minorities in Clinical Trial Research

Some general principles and elements that must be present to promote the inclusion of minorities in clinical research are as follows:

• Existence of active links with grassroots organizations
• Outreach and awareness of the cultural component that leads to minority-relevant research
• Knowledge of motivations for participation, that is, the perceived value of the study, the altruistic component, the desire for peer interaction, and access to care
• Education importance and rationale for participation in clinical trials
• Accessible sites and convenient hours
• Knowledge of the role of the family in decisionmaking

Promoting the inclusion of minorities in clinical trial research is important because the United States has one of the most ethnically diverse populations in the world. A third of the current U.S. population belongs to minority groups, and this proportion is expected to increase steadily. By the early part of the 21st century, today's minority groups are likely to make up more than half of the U.S. population. Information gathered from these populations will be essential for the implementation of health policies and interventions in the future.

The barriers to promoting inclusion of minorities in clinical trial research fall into three general categories:

1. Simple logistical barriers, such as transportation, meals, child or elder care, and time of visits
2. Complex logistical barriers, such as fear of large institutional settings, lack of cultural diversity in the staff, and recruitment and instructional materials in an inappropriate language or at inappropriate literacy levels
3. Barriers related to attitudes, beliefs, and insufficient knowledge, such as fear or distrust of research; lack of familiarity with research procedures such as randomization, masking, and placebo controls; and fears or concerns about interference with primary care or continuity of care

Investigators must recognize the obstacles to minority participation and develop approaches to overcome them. The barriers can be broken, and minority participation can be made more accessible in a number of ways:

• Have members of the target population visit the clinic.

• Hire appropriate staff.

• Understand the need for cultural sensitivity training.

• Include community involvement in the planning process to ensure appropriate language and literacy level.

• Recruit credible spokespeople.

• Seek communication with and endorsement by community leaders.

• Avoid jargon.

• Emphasize benefits gained through participation.

• Ensure a clear understanding of the agendas of the investigators, community, and participants.

• Maintain credibility by never promising what cannot be delivered.

• Never promote activities before they are ready.

The roadmap to success in promoting inclusion of minorities in clinical trial research is characterized by an essential understanding of the target population, including understanding the differences and diversity among subcultures in the Hispanic community. Also, the roadmap to success involves knowing the structure of the community, the process whereby health policy decisions are made, and the opinion makers within the community. In addition, success depends on the recruitment of credible spokespeople, knowing what constitutes a family in the target population, and understanding how decisions are made within the family. Effective means of communication with the target population are through religious organizations, through printed materials and presentations, and through word-of-mouth given by research participants or community advisory board members.

The following practical tips have proven successful:

• Spend time in the community.
• Do library research on medical and scientific literature related to the target population as well as census data, government reports, maps, and newspapers.
• Consult with experts.
• Establish specific goals for recruitment and retention.
• Offer monetary incentives, if necessary.
• Ensure that the investigators, staff, and community understand the design, methods, implementation, and completion of the study.
• Identify individuals or groups that can give access to the community.
• Set up advisory boards to review research plans, informed consent, and recruitment and retention.
• Transmit the research findings back to the community.
• Develop a Web site.

Women and Infants Transmission Study

Dr. Diaz concluded his presentation by describing the NIAID-funded Women and Infants Transmission Study (WITS), a multisite observational study designed to examine the impact of HIV infection on HIV-infected women and their infants. Prospective clinical and laboratory data on HIV infection and disease have been systematically collected at specified intervals from mothers and infants at six sites in the United States: Boston, Chicago, Houston, New York (two sites), and San Juan, Puerto Rico. As of July 2003, WITS had recruited 3,042 women and 2,550 children. The participant distribution is 49 percent African American, 34 percent Hispanic, 12 percent white, and 5 percent others. At all sites, WITS has become the model for successful prevention of mother-to-infant transmission of HIV. In Puerto Rico, the expansion of WITS strategies across the island has achieved a reduction in the number of infected infants from 150 in the 1980s and 1990s to 1.2 in 2003. There have been no infected infants born in the program since 1996. In addition, this highly successful program has achieved long-term retention and continued enrollment.

Dr. Diaz ended by stating that promoting ethnic, racial, and gender diversity in clinical research helps to address gaps in social justice, to end health disparities, and to represent all segments of a multiethnic society. It should be a goal for the 21st century.

The Role of Minority Investigators in Developing Diverse Cohorts in Clinical Research

Dr. Michele K. Evans spoke on the importance of minority investigators. She began by citing the influence of ethnicity, socioeconomic status, and age on health. Health disparities affecting African Americans and Hispanics are evidenced in renal transplantation rates, renal replacement therapy morbidity, evaluation and management of chest pain, treatment of early-stage lung cancer, acute myocardial infarction mortality, access to invasive cardiac procedures, outcome of left ventricular dysfunction, cancer treatment in clinical trials settings, and treatment of pain related to terminal disease.

The sources of health disparities are complex. They are rooted in historic and contemporary inequities related to health care systems, administrative and bureaucratic processes, utilization managers, health care professionals, patients, and clinical and basic biomedical researchers. An Institute of Medicine report on unequal treatment found that racial and ethnic minorities tend to receive lower quality of health care than nonminorities regardless of access factors such as medical insurance and income. Factors that help to explain this disparity include the operation of health care systems, the legal and regulatory climate, discrimination, biases, stereotyping, uncertainty, and patients' cultural preferences. Biomedical researchers contribute to this problem by failing to research disease states that are relevant to minority populations. Unequal treatment leads to the inability to get people to participate in clinical trials.

Of 23,208 full professors teaching in U.S. medical schools, 29 are Native American. Dr. Evans pointed out that the country clearly needs more than 29 people to drive the research infrastructure to look at problems such as diabetes, alcohol abuse, and mental health disorders in the Native American population.

Minority Clinical Researchers: Barriers and Responsibilities

How does a minority in the medical sciences decide to become a researcher? One barrier to that decision is the lack of financial incentives, which are greater in clinical medicine than in basic or clinical biomedical research. Instead of careers in research, minority physicians often enter private practice and become active in community affairs. Minorities in the medical field also need endorsement and encouragement to decide to pursue basic or clinical biomedical research as a valid career choice. Once the choice has been made to enter the field of clinical research, the researcher needs further endorsement to take up minority health and health disparities as a valid research discipline. An additional disincentive is the number of NIH grants given to minority investigators.

In the face of all these barriers, minority researchers bear a responsibility that involves "the vision thing"--they have the ability to bring personal life experiences and perspectives to research. Dr. Evans described an epidemiologic study she is conducting in Baltimore. The study is looking at the effects of race and socioeconomic status on issues of health disparity in a city that has some of the worst health statistics in the Nation. As a medical oncologist who does basic biochemistry of DNA repair in the laboratory, Dr. Evans admits that she lacks the knowledge of an epidemiologist, but she is driven by "the vision thing" to survey 40,000 households in Baltimore to discover the reason for the city's terrible health statistics. "The vision thing" also may explain why underrepresented minority faculty members are 3.2 times more likely than white faculty members to serve on institutional review boards.

Investigators must address barriers to participation in clinical research for themselves as well as for the participants they hope to enroll in the studies. To a minority investigator, clinical research might entail the involvement of social services and an ethical component in the treatment of underserved populations. Research also must be relevant to the perceptions of the participants, and it must address what the researchers want. In addition, environmental logistics must be addressed, including multiple changes of address, the reliability of telephone numbers, lack of transportation, safety issues, childcare, confidentiality, the type of study, and economic concerns.

It is possible to negotiate the barriers to participation of minorities in clinical research by taking the following steps:

• Approach participants through community organizations, such as local churches, tenant associations, neighborhood civic associations, and police departments.
• Take a face-to-face recruitment approach.
• Use researchers of the same race and gender as the participants.
• Create a sense of investment in the study.
• Design the study with a nonresearch benefit for participants.
• Establish a network for participant referral for medical and nonmedical issues.
• Study staff selection based primarily on skill level, followed by diversity.
• Ensure that the spokesperson for the study in the community is a well-trained lay community coordinator, not the principal investigator.
• Offer compensation for time, free transportation, and flexible scheduling.
• Publish a newsletter with study updates, health education information, and features on staff and participants.
• Devise mechanisms for participant feedback.
• Use health fairs, street festivals, and social events to enhance a sense of community.
• Establish contact with participants by phone, mail, or reports.

Setting the Tone for Research: Cultural Proficiency Curriculum

Some medical schools address the issue of the legacy of distrust and attempt to introduce researchers to the notion of cross-cultural communication. A cultural proficiency curriculum teaches the recognition of and appropriate response to key cultural features that affect clinical research and clinical care. The curriculum presents important factors that influence the way health care is delivered and clinical research is conducted. Cultural factors influence the ability to deliver health care and to conduct clinical research. Columbia University, the University of California at San Francisco, and Rush Medical College have developed cultural competence courses for medical students and residents.

Cultural proficiency courses present the scientific rationale for inclusion of underserved populations and minority groups in research projects and for changing the diversity dynamics nationwide; for example, a study of African American culture and clinical research reveals a legacy of mistrust. Cultural proficiency courses also describe and explain the need for cultural competence and sensitivity among clinical researchers and introduce researchers to cross-cultural communication. In addition, the concept of cultural humility and the role of advisory boards are covered topics. Moreover, the courses provide a background for investigators to develop a framework for effective community-based research.

Setting the Research Goals: Operational Goals and Objectives

The operational goals and objectives should include the following:

• Enhancing training opportunities in epidemiology, aging, and health disparities research for local students pursuing careers in public health
• Enhancing participation of minority investigators and minority institutions in clinical research and contributing to building research capabilities at minority institutions
• Developing effective community-based methods of recruiting and retaining minority and socioeconomically diverse participants in clinical research

The role of community advisory boards includes offering advice and counsel, giving consent, building larger communication networks within local neighborhoods, changing perceptions that have inhibited development of substantive working relationships between community members and scientific researchers, and reaching a larger segment of the community for research participation and dissemination of health findings and preventive methods for reducing risk.

Community advisory boards consist of 6 to 28 members who meet 2 to 12 times per year. Membership on community advisory boards can include clergy, school officials, tenant association members, neighborhood residents, politicians, community health professionals, and neighborhood associations.

Questions to be answered on the topic of minority investigators in clinical trials include the following:

• How can the number of minority clinical investigators be increased?
• Why are minority investigators critical for the successful recruitment of diverse subjects?
• What can nonminority investigators do to improve participation rates among diverse segments of the population?
• What is the role of minority and community-based health care providers?
• What is the role of community institutions in recruitment?
• Should investigators design research studies with specific goals and benefits that may appeal to a diverse cohort?
• Is cultural proficiency a factor in clinical research?

Discussion

The breakout session presentation by Drs. Diaz and Evans prompted the following discussion:

• A participant commented on a presentation she attended during which a minority investigator gave a careful and thorough explanation of a study, including the informed consent process.

• Another attendee posed two questions: (1) How are female care providers and/or researchers perceived, supported, and/or undermined by the general Hispanic population? and (2) What is meant by cultural humility? Dr. Diaz responded to the first question by saying that female care providers must be aware of underlying issues, such as childcare, and biases and must be able to bridge the language gap. In response to the second question, Dr. Evans explained that minority investigators must accept the lifestyle of minority participants in clinical trials even though they may not identify with that lifestyle. This type of acceptance is basic to understanding how to reach the populations that most need to participate in clinical research to get access to decent health care.

• The attendee offered a proposal to train more Native American and Hispanic nurse midwives and nurse practitioners to be investigators and to take part in clinical research nationwide.

• Vicki Cargill, from the Office of AIDS Research, offered two points: (1) both minority and nonminority researchers have something to offer in the investigation of health disparities and (2) outreach educators from the community must be offered a fair staff salary. Dr. Diaz concurred that outreach educators often make invaluable contributions to the success of trials.

• Another participant requested talking points on the spiritual or humanistic component of research and on the need for a systematic approach to building an infrastructure in medical education to enlarge the pool of minority investigators.

• Another attendee asked about the concept of building trust in African American and other minority communities with clinical researchers. Is it possible to create trust between the two parties when there has never been a foundation of trust? The attendee asked Dr. Evans if her curriculum covers this issue. Dr. Evans responded that her curriculum addresses the issue of trust from the point of view of the staff, investigators, and participants in a clinical trial.

• Another attendee asked if Tuskegee is the only type case used to examine the issue of mistrust in clinical investigations. Dr. Evans replied that the discussion always begins with Tuskegee.

• Dr. Herman E. Mitchell, from Rho Federal Systems Division, asserted the importance of minority investigators educating nonminority investigators. Dr. Diaz agreed that this type of education is important. Issues of trust are incredibly complex and go far beyond minority issues. They concern medical care and the relationship between patient and practitioner at every level.

• Another attendee asked about promoting clinical trial participation among rural minorities and using local practitioners as co-investigators. Dr. Diaz agreed.