ARTICLE IN BRIEF
Trialists respond to a new study finding a decline in Hispanic representation in clinical trials and offer suggestions for increasing enrollment in neurology studies.
In 1994, the NIH issued new guidelines aimed at strengthening the inclusion of women and minorities in research populations. These guidelines mandated several major new elements to the agency's policy: among them, they stipulated that women and minorities and their subpopulations had to be included in all human participant research, not just clinical research; that the NIH would not allow cost as an acceptable reason for excluding these groups; and that the NIH would initiate programs and support for outreach efforts to recruit these groups into clinical studies.
Fifteen years later, researchers at the University of Michigan set out to discover what difference, if any, these guidelines have made in the enrollment of women and minorities in neurology trials funded by the NINDS — and their findings were surprising.
Although enrollment of both women and African-Americans was significantly higher in trials conducted after the guidelines were enacted compared to the time period before 1995, the enrollment of Hispanic Americans actually declined over time — 7.4 percent in period 1 vs. 5 percent in period 2 (p<0.001).
“Considering that this happened in spite of a strong demographic trend in the opposite direction, as Hispanics have become a much larger proportion of the overall population, this finding is particularly troubling,” said James F. Burke, MD, a clinical lecturer in neurology at the University of Michigan and the lead author of the paper, which appeared in the Jan. 25 Neurology. “Based simply on demographics, one would have imagined that they would also become a larger proportion of our trial population.”
WHY ENROLLMENT IS DECLINING
There may be a number of factors behind the declining enrollment of Hispanics in neurology clinical trials, Dr. Burke theorizes. “First, are we putting our trials in the right types of places? Clinical trials sites tend to be located at large, academic teaching-type hospitals, and while there are exceptions, they may not be in areas that are ethnically and racially diverse.”
Dr. Burke also wonders if there might be a more benign explanation for some of the decline. “As the Hispanic population has grown, it's also become somewhat younger,” he said. “Since the Hispanic population is relatively younger than the white and African-American populations, this may cause an overall decline in disease incidence, which may explain some of the decrease in trial participation.”
Hispanic Americans don't appear to have the same historic skepticism and mistrust of the medical research system that, in the African-American community, has been the understandable result of historical injustices like the 1932-1972 Tuskegee experiments by the US Public Health Service — which studied the natural progression of untreated syphilis — and the story of Henrietta Lacks, whose carcinoma cells were removed for research purposes without her knowledge or permission.
“When researchers have asked Hispanics to participate in trials, they haven't found the cultural resistance seen in the African-American community,” Dr. Burke said. “If it's not that Hispanics are reluctant to participate, maybe it's because we failed to ask them to participate. The truth is, there's much less research into this phenomenon amongst Hispanics than in African-Americans. With African-Americans, lower participation in clinical research is a longer described phenomenon and there has been more explicit energy directed at minimizing it.”
That may be so, but just because the participation of African-Americans in neurology trials has increased since 1995, that doesn't mean it's where it should be in order to ensure their full representation. Barbara Tilley, PhD, Lorne C. Bain Distinguished Professor and director of the Division of Biostatistics at the University of Texas Health Science Center at Houston School of Public Health, and head of the Statistical Coordination Center for the NINDS Exploratory Trials in Parkinson's Disease, reports that it has been “very difficult” to accrue minority patients to Parkinson disease trials.
“Minority recruitment to our Parkinson disease trials has been around 9 percent — that's for all minority groups, including Asian-Americans,” she said. “A number of strategies have been tried, but recruitment is particularly difficult because Parkinson disease, unlike stroke, is not that common. Traditional community approaches, such as going into churches, beauty parlors, and so on, are not effective, because the chance of finding eligible people to recruit that way is very small.”
[Dr. Tilley's observation is all the more troubling in the context of a Dec. 13 study published online in the Archives of Neurology that found that among parkinsonism patients treated at a tertiary movement disorders center, African-Americans and others with lower socioeconomic status had greater disease severity and disability than whites.]
A critical element to recruiting minority patients for participation in clinical trials is establishing relationships with the physicians who serve those patients. “Again, it has to be a large number of physicians, especially when we're doing large trials of patients with early Parkinson disease,” said Dr. Tilley. “And other research we've done has shown that physicians who serve the minority community tend to have fears and suspicions about clinical trials that very much mimic those of their patients, so that gives us a double hurdle to get over.”
Dr. Tilley's group tried to organize meetings — breakfasts, lunches, dinners — that gave minority-serving physicians (both neurologists and general practitioners) a forum to learn about a clinical trial and also about how to manage their own patients with Parkinson disease. “They often weren't interested in spending the time,” Dr. Tilley observed.
But her team did glean some insights from the effort. “The specialists who were successful in recruiting patients were very good at making personal contact. They weren't just sending representatives or sending brochures out. They went out themselves and were very proactive, very understanding of the issues that were faced by minority patients.”
That's been one of a number of keys to success for Philip B. Gorelick, MD, in his efforts to recruit participants for his stroke trials in minority communities. “We have trained our study staff to spend adequate amounts of time to explain our studies, employed study staff from the communities of interest, and provided flexible hours and home study visits or transportation stipends for examinations at the study office,” explained Dr. Gorelick, John S. Garvin Professor and director of the Center for Stroke Research in the Department of Neurology and Rehabilitation at the University of Illinois College of Medicine in Chicago.
Of course, stroke has been widely publicized in some minority communities as a significant health risk. “Thus, stroke has had a head start over some of the other neurological diseases or disorders,” Dr. Gorelick acknowledged. Still, he believes that the barriers to recruitment of minority participants can be broken down for other, less common neurologic diseases with less awareness in minority communities. “We need proper study staff training, community and individual subject education campaigns about the research, genuine commitment and concern on the part of study staff, and diligent work by study staff to overcome deficiencies,” he said.
Leaders of minority communities also need to be involved in research planning from the outset, Dr. Gorelick observed. “They should be part of all elements of the research: the pre-study planning phase, the training and recruitment of study personnel from the minority community of interest, and helping to identify the need for targeted research to provide important information about risk, prevention, or treatment of a disorder that is common to that community,” he said. In a way, it all goes back to the pipeline. “We need programs to enhance the number of minority research scientists available to develop and carry out key, targeted research initiatives in minority communities,” he said.
SUPPORT FROM NINDS
The NINDS is striving to provide support for researchers to increase the enrollment of minorities in clinical trials, said Salina Waddy, MD, a neurologist in the NINDS Office of Minority Health Research. “We have provided a forum for some of the groups performing clinical trials and studies in minority populations to develop Best Practices for enrollment in various minority populations,” she said.
“We recently co-sponsored an enroll-ment workshop with the NHLBI [National Heart, Lung and Blood Institute] to discuss the barriers to recruitment and to identify solutions for improving recruitment in which a significant part of the workshop focused on inclusion of minorities. And we also recently announced the NINDS Diversity Research Education grants, which target health disparities with a stated goal that includes improving the ability to recruit subjects from diverse backgrounds into clinical research protocols.”
One huge gap that could easily be addressed is a continuing lack of information on minority participation in trials. “Although the NIH has specific regulations requiring that this information be reported to them, it's often not making it into publication,” said Dr. Burke.
“In our study, we found that only one-quarter of the publications reported the level of participation of Hispanic Americans. About half reported the number of African-Americans enrolled; that didn't improve over time. Stroke trials do tend to report minority participation more often, possibly because of the awareness of disparities in stroke care. But generally, if you don't tell the scientific masses who is enrolled in your trial, it's hard to raise awareness of this issue.”
That information is the “low-hanging fruit” of the minority trial participation conundrum. “Perhaps the NIH should make funding contingent on reporting these numbers in your publication,” Dr. Burke said. “Or perhaps journal editors should agree to say that they're not going to accept a paper unless that information is there in table form. That's the easy part of the problem. Once we have that, then we can better understand what's happening in terms of trial enrollment. Then we can ask the harder questions about what's driving this phenomenon and how much we should spend to answer these questions, both scientifically and in the interests of social justice and fairness.”