Clinical Researchers Adapting To Mandate For More Diversity In Study Populations

WASHINGTON -- Clinical investigators trying to include more women and minorities in their studies must rethink the traditional researcher-subject relationships and pay more attention to the needs of populations. And while the immediate costs of complying with federal mandates for increasing the use of underrepresented populations as research subjects may be significant, the long-term consequences of not doing so may be considerable, they say. "When I sit on committees, I hear members of re

Sep 16, 1991
Marcia Clemmitt
WASHINGTON -- Clinical investigators trying to include more women and minorities in their studies must rethink the traditional researcher-subject relationships and pay more attention to the needs of populations. And while the immediate costs of complying with federal mandates for increasing the use of underrepresented populations as research subjects may be significant, the long-term consequences of not doing so may be considerable, they say.

"When I sit on committees, I hear members of renowned research institutions stressing the need to carefully separate research from service," says Janet Mitchell, director of the special prenatal clinic at Harlem Hospital in New York. "That's the old thinking: research has to be isolated and protected. But that won't hold water with these new populations."

Mitchell says today's researchers must be able to show how their science contributes to clients' welfare in addition to increasing the world's storehouse of knowledge. " Women, drug users, minorities--they're more sophisticated than the research establishment gives them credit for," says Mitchell. "Their question is, `What are you giving in return? I'm interested in helping if you show me how it'll help me or my children. If you only want me to get your data and your funds, I'm not coming.' " Critics of the use of homogeneous study populations in clinical research charge that the practice ignores hormonal, genetic, and physiological factors that could seriously affect patient outcomes when research is applied. As examples, they point to the different responses of black and white patients to diuretics--drugs that lower salt and water levels--as a treatment for high blood pressure, and to a study conducted largely on men that seemed to show aspirin prevented strokes in men but not in women. Later research showed aspirin to be just as effective in preventing strokes in women.


"It's vital for researchers to admit that the scientific establishment and minority communities have not worked well together in the past," says Diane Stoy, operations director of George Washington Unitersity's Lipids Research Clinic. "For African Americans, Tuskegee lives."

Stoy's reference is to an infamous study, begun in 1934, of 412 black male sharecroppers from Tuskegee, Ala., who were infected with syphilis. For 40 years, researchers observed the men as they suffered and died from the disease, without telling them what the disease was or treating them for it. It's not surprising, say Stoy and others, that many in the black community still harbor grave distrust of medical researchers.

Stoy has headed the Washington, D.C.-based clinic for 17 years. The clinic does cardiovascular research, studying such risk factors as high blood pressure. But, she says, "in a city whose black population is 65.8 percent of the total, I had been very unsuccessful in attracting blacks to the program. I knew something was wrong, but it took a lot of studying and asking to find out how to fix it."

The answer Stoy found, she says, was community involvement. Over the past few years, Stoy has worked with black community leaders, particularly clergy, to increase awareness of the risks of heart disease and the ways clinics might help. "You can't recruit in the same old way," she says. "I used to just do TV and radio ads, sit behind my desk, and wait.

"Now, I get out into the community and talk to people. And I acknowledge the wrongs of the research community in the past. By working closely with the churches and other neighborhood leaders, we stress that we're interested in people's future health." One aspect of her current study is a grant that lists a local church as a subcontractor. "Churches can provide neighborhood sites for taking study data," she notes.

Over the past few years, black participation in clinic programs has soared. While a decade ago a typical population included almost no blacks, the clinic's most recent study boasts a minority recruitment rate of 62 percent. "We're getting better data," Stoy says, "but it's more important than that. It's really about empowering the community in the interest of its own health." --M.C.

In response to such concerns, the National Institutes of Health declared five years ago that medical researchers must include more women and minorities as study subjects in clinical research or give compelling reasons for not including them. But last year the Government Accounting Office reported to Congress that NIH had made no appreciable strides in achieving the goal of diversifying research populations and had no systematic method for enforcing its requirements.

The issue is at the top of the agenda of two new offices at NIH, one on women's studies and the other on minority research. And this summer, the House of Representatives voted as part of its reauthorization of major NIH programs to require the agency to enforce its inclusionary policy in all studies in which it would be applicable.

Although that bill is better known for controversial language relating to fetal tissue use and abortion funding, its provision to spur the use of women and minorities has also drawn fire from the Bush administration. White House officials claim that the provision would make it harder for Secretary of Health and Human Services Louis Sullivan to exercise control over his own department. The bill is expected to reach the president later this fall.

Regardless of the outcome of the bill, researchers must begin to incorporate more women and minorities in their studies to comply with NIH policy. Scientists who have done so cite several elements that must be included when diversifying study populations. Those include:

  • modifying risk/ benefit analyses of clinical trials to account for long-term benefits of diversification as well as short-term savings of using homogeneous populations;

  • improving communication between researchers and study subjects to overcome distrust;

  • abandoning traditional methods for recruitment of research subjects in favor of community-based efforts that involve local institutions, such as churches; and

  • finding ways to meet such primary needs of study populations as child care, access to health care, and a stronger community voice in setting the research agenda. Traditional risk/benefit analysis concludes that clinical research conducted on a homogeneous, rather than a diverse, population ensures the clearest result at the lowest risk of liability and cost. "The rationale for using a homogeneous population is getting a quick--and therefore cheaper--answer about whether an idea is promising," says Gregory W. Siskind, associate dean for research and sponsored programs at Cornell University Medical College's New York Hospital.

    "Suppose you're going to test an HIV vaccine. Most researchers would feel that an antiviral would kill that virus in men, women, blacks, and whites--that there's little question of the vaccine's performance being substantially altered by hormonal or genetic considerations. So most would opt for testing in a homogeneous population, because the number of variables present in a more diverse one might make it more difficult to detect a modest degree of change."

    Siskind notes that some institutions are concerned that because diversifying entails larger groups and a change of focus--causing the research to take longer and therefore become more expensive--fewer studies will be funded.

    But automatic acceptance of such arguments has blinded researchers to the long-term costs of regularly excluding a diverse population, scientists say.

    "Clinical trials are the greatest example we have of applied science," says Lawrence S. Brown, Jr., vice president of the Addiction Research and Treatment Corp. in Brooklyn, N.Y. "And the scientific value of such science lies not just in clear results, but in their therapeutic value. That's why it makes sense to include all relevant variables.

    "Without more inclusive studies, we're going to come up wanting--there'll be more unpredictable side effects, and less benefit than we expected. I've never seen an economic analysis that takes into account these public health issues and the devastating effect they can have on the economy."

    "We may test therapies on homogeneous groups, but we use them to treat a heterogeneous group of patients," says Peter Hawley, medical director of the Whitman-Walker Clinic in Washington, D.C.

    Hawley cites a recent controversy surrounding the anti-AIDS drug AZT as an example of the potential for inaccuracy when testing only a homogeneous population. The initial successful tests of AZT were conducted almost exclusively on white males, Hawley says. But in February of this year, the United States Department of Veterans Affairs released a new study suggesting that AZT may be less effective in treating black men who suffer from AIDS.

    "If more diverse subjects had been included from the start," Hawley says, "these inaccuracies and uncertainties of interpretation could have been avoided."

    NIH officials hope to make clear to grant applicants the importance of using a diverse study population. "It's a question of balance. NIH has decided that people are so in the habit of considering the risk/cost dimension in the simplest way that they just don't think [about other factors]," Siskind says. "They stick with their usual populations out of habit and ignore the possibility that a study could and should appropriately be done on a diverse population.

    "The NIH requirements ask people to think about that up front. In a 10-year study, you shouldn't have to say, five or 10 years down the line--`Egads, we should also be studying this in women!' That kind of decision should be made at the beginning. And, in fact, when you tell people to consider this, they usually conclude they should use diverse groups."

    Arlene Bardeguez, a medical researcher whose studies focus on pregnant women and drugs and AIDS, contends that "it's not inherently more difficult to include women, but you have to develop the tools to do it." Bardeguez, an assistant professor of obstetrics and gynecology at the New Jersey Medical School in Newark, lists child care and transportation among those tools. But she stresses that the most important element is communication.

    "When a woman misses an appointment, you have to ask, `Why is she not coming? Is the baby sick? Does she have transportation? Did she just have a clinic visit two days ago?'

    "It's seldom that she didn't want to come. They may not come on the day you want them to, but they do come. This means you have to listen, so you can build a system responsive to their needs."

    "With women, it's mostly an issue of building trust," says Mary A. Young, an assistant professor of infectious diseases at Georgetown University Medical School in Washington, D.C. "Often, they're initially skeptical." To allay that skepticism, she says, it's important for researchers to understand what the women know about clinical trials and what they believe could help them participate.

    Young is working with a local group of HIV-positive women to develop a survey of how women feel and what they know about research participation. And, she says, she won't be surprised if that survey produces answers that overturn some of her assumptions.

    "For example, we tend to assume that people are always happier when a research trial is conducted in their own neighborhoods," says Young. "But we're finding that for HIV women that may not be true. Many are afraid that neighbors or fellow church members might see them in a neighborhood clinic."

    Another major issue, many researchers who deal with women say, is child care. "For women with children, their own health tends to come second, the child's health and well-being first," says Whitman-Walker's Hawley. "You need to address that in order to get women into trials."

    Among his suggestions are to arrange for a part-time social worker or other employee to assess the women's needs and find a way for schedules to be rearranged or children to be looked after when necessary. "I always try to include money for those things," he says, "though I'm not usually successful."

    Trust is even more of an issue in working with minority groups, say scientists who have done it. Such populations traditionally have had limited access to medical care as well as an adversarial relationship with the research community, these researchers say (see story on page 8). But, they say, greater community involvement in the planning and recruitment processes and greater attention to the study population's needs can go a long way toward solving the problem.

    Richard Hutchinson, a professor of epidemiology at the University of Mississippi Medical School in Jackson, stresses that sustained recruitment efforts for minorities must be community-based, involving neighborhood media and local leaders, such as clergy. For this reason, he adds, it's important to build in a slightly longer lead time to start a study that involves a largely minority population.

    "It takes a little time for people to become aware of a study when they're outside the traditionally solicited population," Harlem Hospital's Mitchell says. "It's important to identify the real community and neighborhood leaders, and discuss the benefits and importance of the study with them.

    "But once the first few people come in and see that they will get good health screening and good data to take to their own doctors, friends will tell friends and the recruitment will take off." Hutchinson reports such a recruitment pattern for a three-year study of hypertension involving an all-black study group: "We anticipate at least 90 percent of our original participants will come back for a second phase of the study."

    Many scientists note that understanding and meeting the vital needs of their subjects also demands that researchers become more involved in the communities from which their subjects will come. "You can't send poor people back to no medical care after a study," says Neil Shulman, an associate professor of medicine at Emory University in Atlanta. "NIH has no mandate to set up clinics so people can receive good primary care, but doctors and research hospitals can try to set up community health centers." Mitchell says that changing the research establishment's ideas that research must be conducted in an institutional setting is one way to ensure that minority populations can participate in research and receive ongoing medical care. "To include low-income populations, you have to have some service component connected with your research," she says. "City hospitals already have that component, so it makes sense to do more research there. Now some of us are trying to prove to the medical establishment that it can be done and done well."

    It's also important, say Emory's Shulman and others, for members of the minority community to be part of research teams and clinic staffs at all levels. "When we first started to work in Atlanta," Shulman says, "we went for advice to a woman who was a leader in the housing projects. She said, `Don't just hire white people from the suburbs to work for you.'

    "We weren't sure we could find enough qualified people. She told us, `Just look.' And we've never had any trouble doing it. I'm not talking just about support staff. It's important to have top-level staff from the community, too. That lets patients feel they're more likely to be respected."

    High levels of community involvement pay dividends for researchers as well as for study participants, says Francisco Fuentes, associate professor of cardiology at the University of Texas Medical School at Houston. "We need to make communities coparticipants in research in more significant ways," Fuentes says. "We can do this by keeping them aware of what research is going on and how it will be important to the community.

    "In return, community leaders can be an invaluable help to us. Often, when you come in from the outside, you're unaware of the extent of particular complications of a disease among a certain population, for example, how much eye complications afflict diabetics in a certain area. You can learn a great deal about multiple risk factors.

    "That's what I mean by making community leaders coparticipants. Their knowledge can be invaluable in developing and refining our research hypotheses."