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.
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Am J Obstet Gynecol. 2018 Apr;218(4):431.e1-431.e12. doi: 10.1016/j.ajog.2017.12.221. Epub 2017 Dec 26.
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.
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.
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.
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.
与基于家族史的检测相比，基于人群的 BRCA1/BRCA2 种系突变检测已被证明在阿什肯纳兹犹太女性中具有成本效益。然而，在塞法迪犹太人群体中仅发现了 3 种阿什肯纳兹 BRCA1/BRCA2 种系突变中的 1 种（185delAG[c.68_69delAG]），5382insC[c.5266dupC]）和 6174delT[c.5946delT]）（185delAG[c.68_69delAG]），因此塞法迪犹太人群体中的 BRCA 突变总体患病率较低（0.7%，而阿什肯纳兹犹太人群体中的患病率为 2.5%）。以前在塞法迪犹太人群体中观察到的这种较低的 BRCA 患病率水平，并未进行 BRCA 检测的成本效益分析。在这里，我们对英国和美国人群进行了成本效益分析，比较了塞法迪犹太女性中基于人群的 BRCA1 检测与基于临床标准/家族史的检测。
建立了一个马尔可夫模型，比较了基于人群的 BRCA1 检测与基于年龄≥30 岁的塞法迪犹太女性的基于家族史的临床标准的终生成本和效果。确定 BRCA1 携带者后，为其提供磁共振成像/乳房 X 光检查和降低风险的手术。报告的费用按 2015 年价格计算。结果包括乳腺癌、卵巢癌和心脏病导致的超额死亡。所有成本和结果均按 3.5%贴现。时间范围是终生，视角是支付方。计算了每质量调整生命年的增量成本效益比。通过单因素和概率敏感性分析评估参数不确定性。
人群检测导致预期寿命增加 12 个月（质量调整生命年=1.00）。英国基于人群的检测的基础贴现增量成本效益比为每质量调整生命年 67.04 英镑，美国为每质量调整生命年 308.42 美元。单向敏感性分析结果稳健。概率敏感性分析显示，在英国，100%的模拟在 20,000 英镑/质量调整生命年的成本效益阈值和美国 100,000 美元/质量调整生命年的成本效益阈值下具有成本效益。情景分析表明，即使绝经前卵巢切除术不能降低乳腺癌风险或激素替代疗法的依从性为零，人群检测在英国和美国人群中仍然具有成本效益。
与基于临床标准的方法相比，基于人群的 BRCA1 检测在塞法迪犹太女性中具有很高的成本效益。这支持改变犹太人群体中基于人群的 BRCA 检测模式，而不论其阿什肯纳兹/塞法迪血统如何。
