NIH Women's Health Study Takes A Giant Step Forward

Date: November 23, 1992 In the first major move toward translating into research the National Institutes of Health's "largest coordinated study of women's health ever undertaken," a coordinating center has been named. Seattle's Fred Hutchinson Cancer Research Center will be overseeing research efforts and analyzing the data from up to 45 clinical centers, the first 15 of which will be identified by NIH in March. Each center will employ about nine researchers. During the course of the Women's Health Initiative (WHI) study-- being spearheaded by NIH director Bernadine Healy--about $600 million will be spent over the next 15 years to find ways to reduce the incidence of a variety of illnesses that afflict women. Although 111 copies of the contract solicitation were requested, Hutchinson was the only institution that actually applied for the $140 million coordination and statistical analysis contract, which was awarded on September 30. Ross Prentice, a noted epidemiologist and director of Hutchinson's public health sciences division, will be principal investigator. Maureen Henderson, head of the center's cancer prevention research program, will be the co-principal investigator. Prentice says he was surprised that his group was the only one to apply for the contract. But he says that he had only two months to prepare his proposal, which he recalls was "a daunting task" because it covers a "broad range of coordinating responsibilities." The job of coordinating the WHI is so large that Prentice had to bring in eight subcontractors, including the Bowman Gray School of Medicine in Winston-Salem, N.C., and the University of California, San Francisco. At Hutchinson, Prentice says, they will deal with the increased work load under the WHI study by adding about 30 new staff members, including seven at the doctoral level, with the rest mainly computer and quality control positions. Nanette Wenger, an Emory University cardiologist with expertise in women's health issues, ascribes Hutchinson's solitary application to both political and scientific factors. "Some members of the scientific community challenged whether this omnibus study is the best way to do it," she says. "And Congress has also taken a challenging view. In an election year, when you have a potential change in Congress, I think a lot of people shy away." Such shyness may not be unwarranted, with Congress welcoming 11 new senators and 109 representatives, many with unknown sentiments toward the WHI. In addition, there is considerable speculation that the WHI's strongest proponent, Healy, a political appointee and former Reagan administration staffer, could be forced to step down after President-elect Bill Clinton moves into the White House (Scott Veggeberg, The Scientist, Sept. 14, 1992, page 1). Daniel McGee, the Loyola University epidemiologist who chaired the contract review committee, says he was "totally shocked" that only one group applied for the grant. However, McGee does feel that the two-month time frame that was allotted to write a proposal of several hundred pages is "nonsense," but it is typical of federal grants. Another reviewer, biomatrician Mikel Aiken of the University of Arizona Cancer Center, says Fred Hutchinson's ascendancy in this field and Prentice's role in advocating the WHI study were probably a big factor in discouraging other applicants. "Hutchinson is clearly in a very strong position, and I'd have to wonder if I'd want to go up against them," he says. Clarence Davis, an epidemiologist at the University of North Carolina, who is among those that requested the solicitation but failed to apply, says it was probably true that many figured Hutchinson had the inside track in getting this contract. But for Davis it was the sheer size of the contract that put him off. "I enjoy doing coordinating center work, but not that big. I didn't know if I wanted to spend the rest of my life on this study and nothing " he says. The competition to become clinical study centers has been considerably more robust, according to NIH officials. The officials would not disclose the number of institutions in the running, citing nondisclosure agreements. It is difficult to predict how many new researchers might be employed at the 45 "vanguard centers" that will conduct the clinical studies, says Prentice. "It will be an important component of research at these centers, but it's not going to be an extremely large budget item," he says. While each of these centers will be provided funding for up to about nine full-time positions--some at the doctoral level and others in supporting positions--it would be an individual decision on the part of the chosen center whether these jobs would be filled by new hires or by reassignment of existing personnel, he says. The WHI has been one of Healy's priorities since taking the post as NIH director, as a way of redressing the lack of attention paid to health problems that largely affect women. The randomized, controlled clinical trial component of the WHI will enroll up to 60,000 postmenopausal women, 50-79 years of age. The trial has three components: to evaluate the effect of a low- fat diet on prevention of breast and colon cancers and of cardiovascular disease; to study how estrogen and progesterone replacement therapy affects the risk of heart disease, osteoporosis, and breast cancer; and to evaluate the effect of calcium and vitamin D supplementation on osteoporosis and colon cancer. The trial will require four years to develop protocols and recruit women subjects and will require nine years of follow- up, say NIH officials. Healy says the Seattle center will be "the central nervous system of the Women's Health Initiative." "The Seattle project will make certain that each clinical center holds to the highest scientific and administrative standards," she says. "The Hutchinson center has extensive experience in coordinating large medical research trials, especially dietary interventions. And it has distinguished itself in the management of other NIH clinical trials of women." The WHI has met with criticism along the way, with some scientists saying the study design has not been peer-reviewed and is poorly formulated. One group of researchers is particularly disturbed over the inclusion of the low-fat diet and breast cancer component, saying there is little scientific evidence that such a link exists. In October, Walter Willett and his colleagues at Harvard Medical School published a report in the Journal of the American Medical Association, demonstrating there is "no evidence of any positive association between intake of total or specific types of fat and risk of breast cancer among either premenopausal or postmenopausal women" (W.C. Willett, et al., JAMA, 268:2037-44). Geoffrey R. Howe of the National Cancer Institute of Canada backed up Willett's findings in an editorial appearing in the same issue (G.R. Howe, JAMA, 268:2080). Howe said the data in this study--dubbed the Nurses' Health Study--which analyzed the dietary fat content of about 90,000 women followed over eight years, "convincingly demonstrates the complete lack of any positive association between fat intake and breast cancer risk in this cohort." WHI officials say they will take this data into consideration and integrate this study with other evidence. But Prentice--a proponent of the dietary fat-breast cancer link--says he hopes the latest Willett report has little impact on the study. "Willett's work has probably been the single strongest argument against the dietary fat association," he says. But he defends the WHI low-fat trial because it will take women down to about 20 percent fat intake, lower than any other study to date. Meir Stampfer, a Harvard epidemiologist and a colleague of Willett, foresees little change in the dietary fat component of the WHI study. "There's so much fervor around this issue that it's gotten to the point where data is not going to change their minds." However, Stampfer and Willett both agree that the low- fat diet component will yield useful information on heart disease and colon cancer risk. Willett also sees problems with the hormonal replacement component of the trial, not because it has no value, but because it probably will significantly reduce the risk of heart disease. During trials of the drug AZT in AIDS patients, for instance, an early positive effect forced researchers, on ethical grounds, to prematurely cease the administration of placebo doses. Willett predicts the same fate will befall the WHI study when it comes to estrogen. Prentice says early cessation of estrogen is possible but not fatal to the study. "Even if it becomes necessary to stop one of the intervention components, it doesn't mean the other components will stop," he says.

NIH Women's Health Study Takes A Giant Step Forward

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