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The massive Women’s Health Initiative estrogen plus progestin clinical trial netted more than $37 billion in savings in the 10 years after it was published, largely by curtailing postmenopausal women’s use of combined hormone therapy, which in turn prevented 126,000 cases of breast cancer and 76,000 cardiovascular events, according to a report published online May 5 in Annals of Internal Medicine.
"The net health yield for women in the United States was approximately 145,000 more quality-of-life-years than would have occurred in the absence of the trial," said Joshua A. Roth, Ph.D., of the public health sciences division, Fred Hutchinson Cancer Research Center and Group Health Research Institute, Seattle, and his associates.
So even though the 2002 trial was one of the most expensive publicly funded studies ever – costing the National Institutes of Health an estimated $260 million in 2012 U.S. dollars – it yielded clinical and economic returns of approximately $140 for every dollar invested in it, they noted.
"Our findings suggest that large public research investments can yield considerable clinical and economic value when targeted to address research questions with great clinical relevance and public health effect," the investigators wrote.
One of the primary debates regarding public funding of research concerns its overall "returns" to society. To estimate the returns of the WHI-EP trial, Dr. Roth and his colleagues developed several mathematical models so they could simulate the 10-year health outcomes of American women aged 50-79 years if the study had never taken place – that is, if it had never been reported that combined hormone therapy (HT) raised the risks of cardiovascular disease, venous thromboembolism, and breast cancer (albeit reducing the risks of fracture and colon cancer).
Publication of those results led to an immediate 50% decrease in the use of combined HT and a continuing decline of 5%-10% per year thereafter, the researchers said.
They compared disease incidence, survival rates, and direct medical expenditures between a "WHI scenario" and a "no WHI scenario" to calculate the net economic and clinical returns of the trial through the year 2012.
Approximately 39.1 million women were eligible for combined HT during the study period. An estimated 5.2 million used combined HT in the WHI scenario, but 9.5 million would have used it if there had never been a WHI, given the usage trends during the years preceding the trial.
Relative to the no-WHI scenario, there were 126,000 fewer cases of breast cancer, 76,000 fewer cases of cardiovascular disease (CVD), and 80,000 fewer cases of venous thromboembolism in the WHI scenario. On the other side of the scale, there also were 263,000 more osteoporotic fractures and 15,000 more cases of colorectal cancer.
"Compared with the no-WHI scenario, the WHI scenario resulted in $35.2 billion in direct medical expenditure savings. Most of the savings came from fewer combined HT users and associated office visits ($26.2 billion), decreased breast cancer incidence ($4.5 billion), and decreased CVD incidence ($2.2 billion), offsetting increases in expenditures for greater fracture incidence ($4.8 billion) and colorectal cancer ($1.0 billion)," Dr. Roth and his associates said (Ann. Intern. Med. 2014;160:594-602).
The WHI scenario, compared with the no-WHI scenario, yielded 145,000 QALYs (quality-adjusted life-years), mainly because of the improved quality of life of women who avoided breast cancer and CVD. This greatly offset the reductions in QALYs that would have been due to increased fractures in the no-WHI scenario.
The net economic return of the WHI was calculated to be $37.1 billion. Savings from reduced use of combined HT drove the early economic value of the trial, and later value was driven by a combination of combined HT expenditure savings and QALY gains.
"This level of value was robust across plausible uncertainty ranges, and remained greater than $20 billion in all simulations that we evaluated," they wrote.
"Our analysis of the economic return from the WHI-EP trial suggests that, in certain circumstances, public investments in large prospective trials with high clinical and public health relevance could provide a similarly large positive rate of return in the long term," the investigators added.
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