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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Patel, Shreeya 
Legood, Rosa 
Evans, D Gareth 
Turnbull, Clare 
Antoniou, Antonis C 

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.

Description

Keywords

BRCA, Sephardi Jewish, cost effectiveness, population testing, Adult, Cost-Benefit Analysis, Female, Genes, BRCA1, Genetic Testing, Hereditary Breast and Ovarian Cancer Syndrome, Heterozygote, Hormone Replacement Therapy, Humans, Jews, Life Expectancy, Magnetic Resonance Imaging, Mammography, Markov Chains, Middle Aged, Mutation, Ovariectomy, Prophylactic Mastectomy, Prophylactic Surgical Procedures, Quality-Adjusted Life Years, United Kingdom, United States

Journal Title

Am J Obstet Gynecol

Conference Name

Journal ISSN

0002-9378
1097-6868

Volume Title

218

Publisher

Elsevier BV
Sponsorship
Cancer Research UK (20861)