Shreeya Patel1, Rosa Legood2, D Gareth Evans3, Clare Turnbull4, Antonis C Antoniou5, Usha Menon6, Ian Jacobs7, Ranjit Manchanda8. 1. Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom. 2. Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom. 3. Centre for Genomic Medicine, Division of Evolution and Genomic Science, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. 4. Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. 5. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. 6. Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom. 7. University of New South Wales, Sydney, New South Wales, Australia. 8. Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom; Department of Gynaecological Oncology, Barts Health National Health Service Trust, Royal London Hospital, London, United Kingdom. Electronic address: r.manchanda@qmul.ac.uk.
Abstract
BACKGROUND: Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost effective compared with family history based testing in Ashkenazi Jewish women. However, only 1 of the 3 Ashkenazi Jewish BRCA1/BRCA2 founder mutations (185delAG[c.68_69delAG]), 5382insC[c.5266dupC]), and 6174delT[c.5946delT]) is found in the Sephardi Jewish population (185delAG[c.68_69delAG]), and the overall prevalence of BRCA mutations in the Sephardi Jewish population is accordingly lower (0.7% compared with 2.5% in the Ashkenazi Jewish population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in the Sephardi Jewish population. Here we present a cost-effectiveness analysis for UK and US populations comparing population testing with clinical criteria/family history-based testing in Sephardi Jewish women. STUDY DESIGN: A Markov model was built comparing the lifetime costs and effects of population-based BRCA1 testing, with testing using family history-based clinical criteria in Sephardi Jewish women aged ≥30 years. BRCA1 carriers identified were offered magnetic resonance imaging/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer, ovarian cancer, and excess deaths from heart disease. All costs and outcomes are discounted at 3.5%. The time horizon is lifetime, and perspective is payer. The incremental cost-effectiveness ratio per quality-adjusted life-year was calculated. Parameter uncertainty was evaluated through 1-way and probabilistic sensitivity analysis. RESULTS: Population testing resulted in gain in life expectancy of 12 months (quality-adjusted life-year = 1.00). The baseline discounted incremental cost-effectiveness ratio for UK population-based testing was £67.04/quality-adjusted life-year and for US population was $308.42/quality-adjusted life-year. Results were robust in the 1-way sensitivity analysis. The probabilistic sensitivity analysis showed 100% of simulations were cost effective at £20,000/quality-adjusted life-year UK and the $100,000/quality-adjusted life-year US willingness-to-pay thresholds. Scenario analysis showed that population testing remains cost effective in UK and US populations, even if premenopausal oophorectomy does not reduce breast cancer risk or if hormone replacement therapy compliance is nil. CONCLUSION: Population-based BRCA1 testing is highly cost effective compared with clinical criteria-driven approach in Sephardi Jewish women. This supports changing the paradigm to population-based BRCA testing in the Jewish population, regardless of Ashkenazi/Sephardi ancestry.
BACKGROUND: Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost effective compared with family history based testing in Ashkenazi Jewish women. However, only 1 of the 3 Ashkenazi Jewish BRCA1/BRCA2 founder mutations (185delAG[c.68_69delAG]), 5382insC[c.5266dupC]), and 6174delT[c.5946delT]) is found in the Sephardi Jewish population (185delAG[c.68_69delAG]), and the overall prevalence of BRCA mutations in the Sephardi Jewish population is accordingly lower (0.7% compared with 2.5% in the Ashkenazi Jewish population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in the Sephardi Jewish population. Here we present a cost-effectiveness analysis for UK and US populations comparing population testing with clinical criteria/family history-based testing in Sephardi Jewish women. STUDY DESIGN: A Markov model was built comparing the lifetime costs and effects of population-based BRCA1 testing, with testing using family history-based clinical criteria in Sephardi Jewish women aged ≥30 years. BRCA1 carriers identified were offered magnetic resonance imaging/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer, ovarian cancer, and excess deaths from heart disease. All costs and outcomes are discounted at 3.5%. The time horizon is lifetime, and perspective is payer. The incremental cost-effectiveness ratio per quality-adjusted life-year was calculated. Parameter uncertainty was evaluated through 1-way and probabilistic sensitivity analysis. RESULTS: Population testing resulted in gain in life expectancy of 12 months (quality-adjusted life-year = 1.00). The baseline discounted incremental cost-effectiveness ratio for UK population-based testing was £67.04/quality-adjusted life-year and for US population was $308.42/quality-adjusted life-year. Results were robust in the 1-way sensitivity analysis. The probabilistic sensitivity analysis showed 100% of simulations were cost effective at £20,000/quality-adjusted life-year UK and the $100,000/quality-adjusted life-year US willingness-to-pay thresholds. Scenario analysis showed that population testing remains cost effective in UK and US populations, even if premenopausal oophorectomy does not reduce breast cancer risk or if hormone replacement therapy compliance is nil. CONCLUSION: Population-based BRCA1 testing is highly cost effective compared with clinical criteria-driven approach in Sephardi Jewish women. This supports changing the paradigm to population-based BRCA testing in the Jewish population, regardless of Ashkenazi/Sephardi ancestry.
Authors: Terri Patricia McVeigh; Deirdre Donnelly; Maryam Al Shehhi; Elizabeth A Jones; Alexandra Murray; Sarah Wedderburn; Mary Porteous; Sally Ann Lynch Journal: Eur J Hum Genet Date: 2019-01-08 Impact factor: 4.246
Authors: Karl Johnson; Katherine W Saylor; Isabella Guynn; Karen Hicklin; Jonathan S Berg; Kristen Hassmiller Lich Journal: Genet Med Date: 2021-12-07 Impact factor: 8.822
Authors: Peter D Beitsch; Pat W Whitworth; Kevin Hughes; Rakesh Patel; Barry Rosen; Gia Compagnoni; Paul Baron; Rache Simmons; Linda Ann Smith; Ian Grady; Michael Kinney; Cynara Coomer; Karen Barbosa; Dennis R Holmes; Eric Brown; Linsey Gold; Patricia Clark; Lee Riley; Samuel Lyons; Antonio Ruiz; Sadia Kahn; Heather MacDonald; Lisa Curcio; Mary Kay Hardwick; Shan Yang; Ed D Esplin; Robert L Nussbaum Journal: J Clin Oncol Date: 2018-12-07 Impact factor: 44.544