Combined hormone therapy clinical trial yields massive economic return

The overall economic return from the WHI E+P trial indicates that changes in practice stemming from the trial provided a net economic return of $37.1 billion over the 10-year period since the main findings were published, providing a return of approximately $140 on every dollar invested in the trial.

The findings, published today in the Annals of Internal Medicine, are the result of collaboration between WHI investigators and faculty at the Hutchinson Institute for Cancer Outcomes Research. The researchers created a disease simulation model to evaluate clinical and economic outcomes for combined hormone therapy (cHT) eligible women since the initial publication of the E+P trial results in 2003.

The study first estimated clinical outcomes for women taking cHT following the study versus a counterfactual scenario where the E+P trial was not conducted and cHT use persisted at historical (pre-2003) trends. Based on the projected clinical outcomes, the study then calculated the net economic return of the trial, less the trial cost.

During the 10 years following publication of WHI E+P findings, the investigators estimated that 4.3 million fewer women used cHT. As a result there were 126,000 fewer breast cancer cases, 76,000 fewer cardiovascular events, 263,000 more osteoporotic fractures, and 15,000 more colorectal cancer cases compared to the no trial scenario. The observed reduction in cHT prescribing saved $49.5 billion in direct medical care costs. In addition, the net health yield for women in the U.S. was approximately 145,000 more quality-adjusted life years than would have occurred in absence of the trial. Assuming that 75% of the change in cHT prescribing can be directly attributed to the WHI, and subtracting the cost of the study itself ($260 million) the net economic return of WHI E+P trial was $37.1 billion.

"The WHI trial is often discussed as having a major impact on post-menopausal combined hormone therapy use, but I'm not aware of any other studies that have projected how many fewer women used combined hormone therapy as a result of the trial," said Joshua Roth, Ph.D., MHA, Hutchinson Institute for Cancer Outcomes Research, and lead author of the study. "It really brings the point home when you crunch the numbers, to see that millions of U.S. women likely stopped or never used combined hormone therapy based on the trial's findings, and that the change in use resulted in important reductions in disease incidence and associated medical spending."

Of the $37.1 billion in net economic return attributable to the WHI E+P trial, $26.4 billion was attributable to medical expenditure savings. These savings were driven by 25 million fewer person-years of cHT use, as well as cost savings from avoided diseases. The remaining $10.7 billion represents the value of additional quality-adjusted life expectancy resulting from lower incidence of breast cancer, cardiovascular disease, and venous thromboembolism.

"The motivation for the first WHI trial was to see if we could prevent heart disease, the number one killer of women. That's why we did it -- the economics never occurred to me," said Garnet Anderson, Ph.D., lead Women's Health Initiative investigator and director of Fred Hutchinson Cancer Research Center's Public Health Sciences Division. "What these findings underscore is the significant role clinical trials play in science and the importance of continuing to find ways to strategically invest public research funds to maximize value to society."

The WHI E+P clinical trial was funded by the National Heart, Lung, and Blood Institute (NHLBI), and its success was realized by dedicated study participants who contributed their time to help answer important research questions. Today's report on the $37.1 billion economic return of its E+P trial suggests that large public research investments can yield considerable clinical and economic value when targeted to address research questions with high clinical relevance and public health impact.

"It is important to consider the potential value of studies when making decisions about how to invest limited public research dollars," said Scott Ramsey, M.D., Ph.D., Director of Hutchinson Institute for Cancer Outcome Research. "Many stakeholders have talked about the high cost of the WHI estrogen plus progestin trial, but few have considered the potential value of the trial. These findings show that the trial was a high-value use of public funds with a substantial return on investment."