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Lack of minority clinical investigators behind dearth of minority subjects in trials.
Views about racial disparities have changed in recent years. It is no longer the consensus that minority groups are less likely to participate in clinical research than nonHispanic whites due to historical abuses or even societal prejudices in general.
Kenneth A. Getz
New data suggests that under-representation of minority volunteers in clinical trials has a lot to do with the race and ethnicity of the clinical research investigator. This is one of the major findings of a study that my colleague, Laura Faden, and I recently completed. The Tufts Center for the Study of Drug Development (Tufts CSDD) study found that minority physicians participate in clinical research far less often than their white counterparts—most notably in FDA-regulated clinical trials funded by industry. Whereas 9.3% of all white physicians actively participate as principal investigators in industry-funded clinical trials, only 3.7% of minority physicians do.
Although minority physicians are no less interested in participating in clinical research than white physicians, minority investigators tend to conduct and initiate only about half the number of trials annually as their white counterparts. They're also younger and have a more limited clinical research infrastructure.
"The discrepancy between government- and industry-funded trials should come as no surprise," said Priscilla Igho-Pemu, MD, MS, director of clinical trials in the Clinical Research Center at Atlanta's Morehouse School of Medicine. "Only trials funded by the National Institutes of Health (NIH) are required to involve minorities. If not, you need a strong scientific rationale to not include them...not just that it's inconvenient or they're slow to recruit or noncompliant."
Since the mandate went into effect in 1993, the NIH has "constantly refined inclusion requirements [and] monitored and publicly reported progress toward more balanced representation," commented Alfonso Alanis, MD, chairman and chief executive officer of Anaclim, an Indianapolis, IN-based clinical research organization that specializes in minority participation. The regulations, he believes, drove a lot of positive change in NIH-funded clinical research.
"Minorities are woefully underrepresented even in studies of diseases, like diabetes, that disproportionately affect them," explained Alanis. To not have proper representation of impacted populations creates issues of scientific integrity and relevance. "There is now ample evidence that different racial and ethnic groups can respond differently to the same treatments. Given the significant growth of minority populations in the U.S., exclusion is also hard to justify from a social justice perspective," he said. According to the U.S. Census Bureau, by the year 2050, more than half of the U.S. population will be comprised of minority communities, up from 37% in 2004.
The commonly held belief that under-representation of minority volunteers in clinical trials is due to the legacy of Tuskegee and distrust of the research establishment was challenged by a December 2005 PLoS Medicine article, conducted by David Wendler, PhD, and his colleagues. "We found that minorities are at least as willing to participate in clinical research studies as long as they are eligible, know about it, and are invited to volunteer," said Wendler, director of the unit on vulnerable populations in the department of bioethics at the NIH. Wendler believes the largest barrier to minority participation is access. "A lot of studies are conducted largely by white investigators in inaccessible places to many minorities," said Wendler. There are also a host of socioeconomic barriers, including the inability to take time off from work or to afford the transportation costs.
"In inner city Baltimore, it has been relatively easy to attract male African-Americans to participate in research at the National Institute of Drug Abuse simply because that's their home turf," Wendler said.
"It's still often true that people get in a trial as the result of a referral from their primary care and specialty care doctor. But minority physicians in the best position to refer would-be minority participants may not have colleagues from medical school running clinical trials. They may not even be able to spare the time to make a referral," said Wendler. "And minorities in lower socioeconomic groups have disproportionately more co-morbidities that can make meeting a study's exclusion criteria an obstacle. But access and knowledge about trials are the greatest hindrances overall," he said.
"We recommend that [sponsors] open up sites in minority communities and involve minority clinicians and investigators," said Wendler. "In a lot of cases, it's relatively easy to do. This isn't an intractable problem."
Morehouse's Clinical Research Center has successfully tackled some of the root causes of racial disparities: minority physicians are less likely to be trained in the clinical trial process, lack sufficient resources and contacts to identify trials, and have limited capacity to respond quickly when they're offered clinical trials. In 2002, the Clinical Research Center created the Community Physician Network (CPN) to overcome these hurdles while increasing the quality of care minority patients receive, says Igho-Pemu. Over 165 practices, more than half primary care, are in the network. CPN provides training and mentoring to practices interested in participating in trials.
To enable CPN practices to more rapidly identify potential trial participants, four disease-specific registries—for hypertension, diabetes, metabolic syndrome, and heart failure—were created. "These registries provide a good cross-sectional view of what goes on in a practice and serve as a resource for evaluating clinical trial feasibility," said Igho-Pemu. She added that the "longitudinal" view provided by an electronic medical record (EMR) is an even better method for identifying potential participants, but is cost prohibitive for most solo and small-group practices at this time.
"Due to heath literacy issues, recruitment of minority patients happens best via face-to-face at health fairs rather than newspaper advertisements," said Igho-Pemu. In the past year, the Clinical Research Center has participated in 24 health fairs, screened 2304 people, and enrolled 708 volunteers into studies. More than 1400 volunteers in its active participant database are waiting for suitable studies.
To help practices set up the needed administrative structure for trials, CPN has three study coordinators available to help train sites' own coordinators. For the first time in March, it enlisted a professional research consultant to provide two days of Good Clinical Practice training to principal investigators and their study coordinators. CPN is now soliciting entry-level trials from industry sponsors for the 150 attendees, with the availability of a central IRB to expedite the approval process. It also seeks to establish master agreements with industry sponsors to eliminate contract uncertainties for fledgling investigators.
For the past three years, Anaclim has been actively recruiting minority populations using one seemingly simple strategy: inviting minority physicians and practices with high volumes of minority patients to participate as investigational sites. The CRO maintains a database of 4000 minority physicians, about 400 of which have been utilized to date for 17 clinical trials.
"We guarantee to provide patient populations that mirror the epidemiology of the disease we're asked to study," says Alanis. "Half of the time, we're hired by sponsors to do just the minority piece of a clinical trial."
According to Alanis, minority principal investigators tapped by Anaclim are eager to participate in clinical trials. "They work hard and the quality of their work is very good. Their patients, who are often of the same race and ethnicity, put a great deal of trust in them. Hispanic and African-American physicians, in particular, tend to return to their home community to practice after medical school. Their patients are relatively easy to recruit into clinical trials, though they typically ask more questions about trial design and safety precautions because they want to be reassured that nothing bad is going to happen to them," said Alanis.
Alanis has found that minority patients, existing disproportionately in lower socioeconomic stratums, tend to have special transportation, childcare, and communication needs that must be addressed if they are to be recruited and retained in studies. "Without some sort of compensation for missed time from work, many patients simply can't afford to make the study visits," he added.
Pharmaceutical and biotechnology companies, the primary funding sources for trials of new medical interventions, have become far more aware of the need to address racial and ethnic differences in their clinical studies. This will require research sponsors to broaden their focus beyond performance and outcomes, accept the higher cost associated with minority patient inclusion, and willingly go the extra mile to identify minority investigators.
The National Medical Association, which represents African-American physicians, is hopeful that pressure from prescribing minority physicians will help spur change. The organization has instructed members to ask drug company sales representatives to provide clinical trial data specific to African-American subjects if available.
On a broad scale, new health policies are needed. At the Baylor College of Medicine in Houston, Armin Weinberg, PhD, is heading up the four-year EDICT (Eliminating Disparities in Clinical Trials) project aimed at identifying feasible policy strategies and creating synergy between groups that have independently discovered promising solutions.
EDICT, initially sponsored by a grant from Genentech to Baylor and the Intercultural Cancer Council (ICC), "brings together stakeholders representing the public, private, and nonprofit sectors and focuses on erasing disparities in the areas of oncology and asthma trials," said Weinberg, director of the Chronic Disease Prevention and Control Research Center. "Nonprofits fund a fair amount of research but, like industry, aren't required to include representative samples of subpopulations."
Weinberg added that EDICT has identified nine areas of opportunity for impacting health policy, including expanding publication review procedures to cover inclusion efforts, providing insurance coverage for trial participants, and improving the conversation between physicians and patients about the clinical trial option. "The recommendations will be launched at an ICC symposium in April 2008 before being disseminated nationally," said Weinberg.
Two spin-off projects have emerged from EDICT, including application of National Standards on Culturally and Linguistically Appropriate Services to the clinical trials process. Team members are also nominating best practices and policies to include in a "backpack" of tools for eliminating disparities. A separate arm of EDICT is field-testing educational and support interventions for increasing clinical trial enrollment in underrepresented patient groups. These demonstration projects will result in a "toolkit" that can be easily modified to target any underrepresented population.
Meaningful progress in eliminating racial disparities may require some degree of encouragement and/or enforcement by the U.S. FDA. "At the very least, the agency needs to start enforcing existing regulations that require new drug applications to report the ethnicity of patients in trials," said Alanis. "My hope is that pharmaceutical and biotech companies soon come to realize that the inclusion of minorities is not only the right thing to do, but provides a competitive advantage."
For a copy of the results of the recent Tufts CSDD report quantifying minority disparities among clinical investigators, contact me or Peg Hewitt at Peg.Hewitt@tufts.edu
Kenneth A. Getz MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: email@example.com