Cost-Effectiveness Analyses of Aromatase Inhibitors versus Tamoxifen in Early Stage Breast Cancer

Background: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policyrelevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. Methods: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. Results: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Conclusion: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy. Citation: John-Baptiste AA, Wu W, Rochon P, Anderson GM, Bell CM (2013) A Systematic Review and Methodological Evaluation of Published Cost-Effectiveness Analyses of Aromatase Inhibitors versus Tamoxifen in Early Stage Breast Cancer. PLoS ONE 8(5): e62614. doi:10.1371/journal.pone. 0062614 Editor: Todd W. Miller, Dartmouth, United States of America Received December 17, 2012; Accepted March 22, 2013; Published May 6, 2013 Copyright: 2013 John-Baptiste et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Team Grant [Grant number OTG-88591] from the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism and Diabetes (http://www.cihr-irsc.gc.ca/e/13521.html), Cancer Care Ontario (https://www.cancercare.on.ca), and the Ontario Institute for Cancer Research (http://oicr.on.ca) (through funding provided by the Ministry of Health and Long-Term Care http://www.health.gov.on.ca/en/and the Ministry of Economic Development and Innovation http://www.ontariocanada.com/ontcan/1medt/en/home_en.jsp of the Government of Ontario). Ava John-Baptiste was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research http://www.cihr-irsc.gc. ca/e/193.html (through funding provided by the Ministry of Health and Long-Term Care). Chaim Bell is supported by a Canadian Institutes of Health Research/Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care (http://www.patientsafetyinstitute.ca/English/research/PatientSafetyPartnershipProjects/patientSafetyResearchChair/Pages/default. aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ava.john-baptiste@wchospital.ca