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Economic Return From the Women's Health Initiative Estrogen Plus Progestin Clinical Trial: A Modeling StudyEconomic Return From the WHI Estrogen Plus Progestin Clinical Trial

Joshua A. Roth, PhD, MHA; Ruth Etzioni, PhD; Teresa M. Waters, PhD; Mary Pettinger, MS; Jacques E. Rossouw, MD; Garnet L. Anderson, PhD; Rowan T. Chlebowski, MD, PhD; JoAnn E. Manson, MD, DrPH; Mark Hlatky, MD; Karen C. Johnson, MD, MPH; and Scott D. Ramsey, MD, PhD
[+] Article and Author Information

From the Fred Hutchinson Cancer Research Center and Group Health Research Institute, Group Health Cooperative, Seattle, Washington; University of Tennessee Health Science Center, Memphis, Tennessee; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles, Medical Center, Torrence, California; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and Stanford Medical School, Stanford University, Stanford, California.

Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank the WHI participants, clinical sites, investigators, and staff for their dedicated efforts.

Grant Support: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services (contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). Dr. Roth is supported by National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services (grant T32 AG027677).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2348.

Reproducible Research Statement: Study protocol: Not applicable. Statistical code and data set: Available from Dr. Roth (jroth@fhcrc.org).

Requests for Single Reprints: Scott Ramsey, MD, PhD, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M3-B-232, Seattle, WA 98109; e-mail, sramsey@fhcrc.org.

Current Author Addresses: Drs. Roth, Etzioni, and Ramsey and Ms. Pettinger: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M3-B-232, Seattle, WA 98109.

Drs. Waters and Johnson: Department of Preventive Medicine, University of Tennessee Health Science Center, 66 North Pauline Street, Suite 633, Memphis, TN 38163.

Dr. Rossouw: National Heart, Lung, and Blood Institute, PO Box 30105, Bethesda, MD 20824-0105.

Dr. Anderson: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M3-A410, PO Box 19024, Seattle, WA 98109.

Dr. Chlebowski: Harbor–University of California, Los Angeles, Medical Center, 1000 West Carson Street, Torrance, CA 90502.

Dr. Manson: Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, 3rd Floor, Boston, MA 02215.

Dr. Hlatky: Stanford University School of Medicine, Health Research and Policy Redwood Building, Room 150, 259 Campus Drive, Stanford, CA 94305-5405.

Author Contributions: Conception and design: J.A. Roth, R. Etzioni, T.M. Waters, G. Anderson, J.E. Manson, K.C. Johnson, S.D. Ramsey.

Analysis and interpretation of the data: J.A. Roth, R. Etzioni, T.M. Waters, M. Pettinger, R.T. Chlebowski, J.E. Manson, S.D. Ramsey.

Drafting of the article: J.A. Roth, R. Etzioni, S.D. Ramsey.

Critical revision of the article for important intellectual content: J.A. Roth, R. Etzioni, T.M. Waters, J. Rossouw, G. Anderson, R.T. Chlebowski, J.E. Manson, M. Hlatky, K.C. Johnson, S.D. Ramsey.

Final approval of the article: J.A. Roth, R. Etzioni, T.M. Waters, M. Pettinger, J. Rossouw, G. Anderson, R.T. Chlebowski, J.E. Manson, M. Hlatky, K.C. Johnson, S.D. Ramsey.

Provision of study materials or patients: J.A. Roth, R.T. Chlebowski, K.C. Johnson, J.E. Manson.

Statistical expertise: J.A. Roth, R. Etzioni, M. Pettinger.

Obtaining of funding: J.A. Roth, J. Rossouw, G. Anderson, J.E. Manson, S.D. Ramsey.

Administrative, technical, or logistic support: J.A. Roth, J. Rossouw, G. Anderson, J.E. Manson, S.D. Ramsey.

Collection and assembly of data: J.A. Roth, J. Rossouw, R.T. Chlebowski, J.E. Manson.


Ann Intern Med. 2014;160(9):594-602. doi:10.7326/M13-2348
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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.

Figures

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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.

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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.

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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.

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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.

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