Published April 18, 2013
It was, admittedly, a long shot. Twenty years ago, faculty in the UB School of Medicine and Biomedical Sciences applied for a large National Institutes of Health contract called the Women’s Health Initiative, the landmark women’s health study and the largest clinical trial ever undertaken in the U.S.
“At the time, UB had had limited experience with major multi-centered clinical trials,” recalls Jean Wactawski-Wende, then an assistant professor in the Department of Gynecology-Obstetrics in the medical school who wrote the application with Maurizio Trevisan, an expert in preventive cardiology who at the time was professor and incoming chair of the Department of Social and Preventive Medicine.
“We weren’t a powerhouse like Harvard, but we worked hard to put our best foot forward,” says Wactawski-Wende, now professor and associate chair of social and preventive medicine, and vice provost for strategic initiatives. “We literally spent three months, full time, writing that application. We knew we had the talent to do this, but not the national reputation. We figured that we would get the pink sheets with reviewers’ criticisms and respond to the second round when additional centers would be added to see if we could better our score.
“As it turned out, the hard work paid off and we were one of the top reviewed applications. The lesson is: Do your best, because you never know!”
The announcement that UB had been chosen as one of the 16 vanguard centers came through on March 30, 1993.
Along with such institutions as the University of Pittsburgh, Northwestern University and Brigham and Women’s Hospital in Boston, UB was awarded a $13 million, 12-year contract, making it one of just 16 Vanguard Clinical Centers for women’s health in the U.S.; another 24 centers were added two years later.
In 2005, UB successfully competed for a five-year extension of the original contract. In 2010, based on UB’s success as a vanguard center, the university received an $8.2 million award from the National Heart, Lung and Blood Institute to administer a new round of studies that extend the WHI until 2015, and now leads the entire Northeast region. The four remaining regional centers that coordinate what were 40 centers are Buffalo, Stanford, Wake Forest and Ohio State. The Fred Hutchinson Cancer Research Center in Seattle serves as the coordinating center for the study.
In this new role, UB oversees the scientific direction and the participant contacts of the Northeast region's nine institutions: Harvard University, Brown University, Albert Einstein College of Medicine, University of Massachusetts at Worcester, Stony Brook University, George Washington University, University of Medicine and Dentistry of New Jersey and Medstar Health Research Institute, in addition to UB.
WHI is the largest study ever undertaken in the U.S., originally involving more than 162,000 women across the nation, including nearly 4,000 in Buffalo. The goal of WHI was to gather essential clinical data on the major diseases affecting women, on whom remarkably few studies had ever been done.
WHI is best known for what it revealed about hormone therapy through the clinical trials done in these postmenopausal women.
“It completely changed what we thought about hormone therapy,” says Wactawski-Wende. She notes that prior to the WHI, one-third of the prescriptions for the most commonly prescribed hormone replacement were given for chronic disease prevention before a single clinical trial had been done to determine that hormone therapy actually was able to prevent chronic diseases, such as cardiovascular disease.
“The conventional thinking at the time, all from observational evidence, was that women were being protected from heart disease by estrogen therapy,” she says. “And while observational evidence often turns out to be correct, in this case it turned out that it wasn’t. It wasn’t until we saw all the data that we could see that many assumptions about hormone therapy were a likely result of ‘healthy-user bias.’”
At UB, the WHI award opened horizons for researchers on multiple levels, says Wactawski-Wende.
“Having the vanguard center here has been an amazing training ground,” she says. “Being a multicenter study allowed UB to be affiliated with so many powerhouses around the country and some of the best investigators in the field. It’s been great for our younger faculty.”
Data collected by UB’s WHI researchers have been used by UB faculty studying everything from connections between periodontal disease and cancer, genome-wide associations with disease, metabolic syndrome and the role vitamin D plays in chronic disease. These data also have been a goldmine for master’s degree and doctoral students who use them as a jumping-off point for their own research.
Perhaps the most important piece of the WHI research at UB was the development of a comprehensive biospecimen bank, containing hundreds of thousands of biological samples provided by the Western New York women who participate in the WHI. “We have samples of blood, saliva, plaque, urine, DNA, breast milk and tumor blocks. This has been a goldmine for additional research,” says Wactawski-Wende.
Those samples and all the data that WHI continues to collect, she says, are keys to some of the most valuable research ever done on women’s health. This treasure trove of information has led to the publication of nearly 1,000 scientific publications from all of the WHI institutions and investigators. About 1,000 more publications are in the pipeline. In addition, the biorepository has allowed UB to apply for some very ambitious grants. “You have to show that you have this kind of capacity,” Wactawski-Wende notes.
“And in addition to the initial WHI contract and extension studies of over $21 million, UB has attracted over $12 million in additional funding in the WHI center, which we obtained because of this critical infrastructure which we have now,” says Wactawski-Wende.
The women who participated are an important part of the story, too, especially in Buffalo. “Recruiting participants for clinical trials is always just plain hard,” says Wactawski-Wende, “but the women of Western New York stepped up. UB was the first center out of the initial 16 that completed recruiting; in fact, we over-recruited!
“Western New York is just a great location for doing clinical studies. Women in this region are very altruistic, willing to participate in a study to help future generations of women,” she says. “Buffalo is really the city of good neighbors. These women—some of whom are now in their 90s—wanted to do something meaningful, to help someone else. They did it for their daughters and granddaughters.”
In addition to providing samples, they respond to detailed questionnaires every year about their health habits and diets. That will continue at least until 2015.
“We are already planning for the next submission to extend the study to 2020,” says Wactawski-Wende. “It has been an amazing experience.”