Economic return from the Women's Health Initiative estrogen plus progestin clinical trial: a modeling study

Abstract

Background: The findings of the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial led to a substantial reduction in use of combined hormone therapy (cHT) among postmenopausal women in the United States. The economic effect of this shift has not been evaluated relative to the trial's $260 million cost (2012 U.S. dollars).

Objective: To estimate the economic return from the WHI E+P trial.

Design: Decision model to simulate health outcomes for a "WHI scenario" with observed cHT use and a "no-WHI scenario" with cHT use extrapolated from the pretrial period.

Data sources: Primary analyses of WHI outcomes, peer-reviewed literature, and government sources.

Target population: Postmenopausal women in the United States, aged 50 to 79 years, who did not have a hysterectomy.

Time horizon: 2003 to 2012.

Perspective: Payer.

Intervention: Combined hormone therapy.

Outcome measures: Disease incidence, expenditure, quality-adjusted life-years, and net economic return.

Results of base-case analysis: The WHI scenario resulted in 4.3 million fewer cHT users, 126,000 fewer breast cancer cases, 76,000 fewer cardiovascular disease cases, 263,000 more fractures, 145,000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100,000 per quality-adjusted life-year.

Results of sensitivity analysis: The 95% CI for the net economic return of the trial was $23.1 to $51.2 billion.

Limitation: No evaluation of indirect costs or outcomes beyond 2012.

Conclusion: The WHI E+P trial made high-value use of public funds with a substantial return on investment. These results can contribute to discussions about the role of public funding for large, prospective trials with high potential for public health effects.

Primary funding source: National Heart, Lung, and Blood Institute.

Figure 1

Disease-simulation model simplified schematics for the cHT decision tree and Markov state transition model structure. Panel A illustrates the structure of the simulation model decision tree. At the end of the decision tree, women entered the Markov model (“M”) (panel B) and were tracked for long-term health outcomes. Once women transitioned into a disease state, survival, expenditure, and quality-adjusted life-year outcomes were stratified into initial vs. subsequent years in that state. Note that the cHT ever user Markov models divide the “no disease of interest” state into current cHT users and cHT stoppers. cHT = combined hormone therapy; HT = hormone therapy. * Combined hormone therapy– eligible women entered the model from 2003 until 2012. The first cohort (2003) comprised prevalent hormone therapy users and never users, and subsequent cohorts (2004 –2012) comprised never users. † The outcomes of interest are coronary heart disease, coronary artery bypass graft/percutaneous transluminal coronary angioplasty, stroke, deep venous thrombosis, pulmonary embolism, breast cancer, endometrial cancer, colorectal cancer, hip fracture, vertebral fracture, and other osteoporotic fracture. Each outcome of interest is tracked as a separate health state in the Markov model.

Figure 2

Absolute differences in 10-y disease incidence between WHI and no-WHI scenarios. Positive values reflect increased disease incidence in the WHI scenario vs. the no-WHI scenario, and negative values reflect decreased disease incidence in the WHI scenario vs. the no-WHI scenario. Errors bars represent 95% CIs as generated by sensitivity analysis. CABG = coronary artery bypass graft; PTCA = percutaneous transluminal coronary angioplasty; WHI = Women’s Health Initiative.

Figure 3

Differences in 10-y direct medical expenditure between WHI and no-WHI scenarios. Positive values reflect greater expenditure related to changes in the incidence of the listed condition in the WHI scenario vs. the no-WHI scenario, and negative values reflect reduced expenditure for listed condition. Errors bars represent 95% CIs as generated by sensitivity analysis. CABG = coronary artery bypass graft; PTCA = percutaneous transluminal coronary angioplasty; WHI = Women’s Health Initiative.

Figure 4

Annual net economic return created by expenditure savings and QALY gains in the WHI and the no-WHI scenarios. QALY = quality-adjusted life-year; WHI = Women’s Health Initiative.