Abstract
To assess the cost effectiveness from a Canadian perspective of index patient germline BRCA testing and then, if positive, family members with subsequent risk-reducing surgery (RRS) in as yet unaffected mutation carriers compared with no testing and treatment of cancer when it develops. A patient level simulation was developed comparing outcomes between two groups using Canadian data. Group 1: no mutation testing with treatment if cancer developed. Group 2: cascade testing (index patient BRCA tested and first-/second-degree relatives tested if index patient/first-degree relative is positive) with RRS in carriers. End points were the incremental cost-effectiveness ratio (ICER) and budget impact. There were 29,102 index patients: 2,786 ovarian cancer and 26,316 breast cancer (BC). Using the base-case assumption of 44 percent and 21 percent of women with a BRCA mutation receiving risk-reducing bilateral salpingo-oophorectomy and risk-reducing mastectomy, respectively, testing was cost effective versus no testing and treatment on cancer development, with an ICER of CAD 14,942 (USD 10,555) per quality-adjusted life-year (QALY), 127 and 104 fewer cases of ovarian and BC, respectively, and twenty-one fewer all-cause deaths. Testing remained cost effective versus no testing at the commonly accepted North American threshold of approximately CAD 100,000 (or USD 100,000) per QALY gained in all scenario analyses, and cost effectiveness improved as RRS uptake rates increased. Prevention via testing and RRS is cost effective at current RRS uptake rates; however, optimization of uptake rates and RRS will increase cost effectiveness and can provide cost savings.
Highlights
Testing remained cost effective versus no testing at the commonly accepted North American threshold of approximately Canadian dollars (CAD) 100,000 per quality-adjusted life-year (QALY) gained in all scenario analyses, and cost effectiveness improved as risk-reducing surgery (RRS) uptake rates increased
44 percent of BRCA positive women underwent risk-reducing bilateral salpingo-oophorectomy (RRBSO) at age 54 years and 21 percent of BRCA positive women underwent risk-reducing mastectomy (RRM) at age 44 years [20;21], resulting in 127 fewer epithelial ovarian cancer (EOC) cases, 104 fewer breast cancer (BC) cases, and 21 fewer deaths. These outcomes were achieved at an additional cost of CAD 11,777,696 (USD 8,319,986) with a QALY gain of 788, resulting in an incremental cost-effectiveness ratio (ICER) of CAD 14,942 (USD 10,555) per QALY gained, which is cost effective at the commonly accepted Canadian willingness to pay threshold of CAD or U.S dollars (USD) 100,000 per QALY gained
A longer time period was not modeled, cost savings would continue to occur in all years after this period. This Canadian analysis demonstrates that current genetic testing of patients with EOC or BC and their family members for BRCA mutations followed by RRS prevents cancer cases and deaths, at an incremental cost which is considered cost effective
Summary
To assess the cost effectiveness from a Canadian perspective of index patient germline BRCA testing and if positive, family members with subsequent risk-reducing surgery (RRS) in as yet unaffected mutation carriers compared with no testing and treatment of cancer when it develops. Group 1: no mutation testing with treatment if cancer developed. Using the base-case assumption of 44 percent and 21 percent of women with a BRCA mutation receiving risk-reducing bilateral salpingo-oophorectomy and risk-reducing mastectomy, respectively, testing was cost effective versus no testing and treatment on cancer development, with an ICER of CAD 14,942 (USD 10,555) per quality-adjusted life-year (QALY), 127 and 104 fewer cases of ovarian and BC, respectively, and twenty-one fewer all-cause deaths. Prevention via testing and RRS is cost effective at current RRS uptake rates; optimization of uptake rates and RRS will increase cost effectiveness and can provide cost savings
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