Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women.

Abstract

BACKGROUND: Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost-effective compared to family-history(FH) based testing in Ashkenazi Jewish(AJ) women. However, only one of the three AJ BRCA1/BRCA2 founder-mutations (185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT)) is found in the Sephardi Jewish(SJ) population (185delAG(c.68_69delAG)) and the overall prevalence of BRCA mutations in the SJ population is accordingly lower (0.7% compared to 2.5% in the AJ population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in SJ. Here we present a cost-effectiveness analysis for UK and US populations comparing population-testing with Clinical-criteria/FH-based testing in SJ women. METHODS: A Markov model was built comparing the lifetime costs-&-effects of population-based BRCA1-testing with testing using FH-based clinical criteria in SJ women ≥30years. BRCA1-carriers identified were offered MRI/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer(BC), ovarian cancer(OC) and excess deaths from heart disease. All costs-&-outcomes are discounted at 3.5%. The time horizon is life-time, and perspective is payer. The incremental-cost-effectiveness-ratio (ICER) per quality-adjusted life-year (QALY) was calculated. Parameter uncertainty was evaluated through one-way and probabilistic-sensitivity-analysis (PSA). RESULTS: Population-testing resulted in gain in life-expectancy of 12months (QALY=1.00). The baseline discounted ICER for UK population-based testing =£67.04/QALY and for US population=$308.42/QALY. Results were robust in the one-way sensitivity analysis. The PSA showed 100% of simulations were cost-effective at £20,000/QALY UK and the $100,000/QALY US WTP thresholds. Scenario analysis showed, population-testing remains cost-effective in UK and US populations even if pre-menopausal oophorectomy does not reduce BC-risk or if hormone-replacement-therapy compliance is nil. CONCLUSION: Population-based BRCA1- testing is highly cost-effective compared to clinical-criteria driven approach in SJ women. This supports changing the paradigm to population-based BRCA- testing in the Jewish population regardless of Ashkenazi/Sephardi ancestry.