Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women
Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women
复制标题
DOI：
10.1093/jnci/djx265
复制
发表时间：
2018-07-01
影响因子：
10.3
通讯作者：
Legood, Rosa
中科院分区：
文献类型：
--
作者：
Manchanda, Ranjit;Patel, Shreeya;Legood, Rosa
背景：以人群为基础的小组检测卵巢癌(OC)/乳腺癌(BC)高、中外显性基因突变的成本效益尚不清楚。我们评估了基于人群的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2突变检测与临床标准/家族史(FH)检测在未选择的普通人群女性中的成本-效果。方法：比较基于标准/FH的BRCA1/BRCA2检测与BRCA1/BRCA2/RAD51C/RAD51C/RAD51D/BRIP1/PALB2检测在那些满足临床标准/强FH的癌症(>；=10%BRCA1/BRCA2概率)和所有30岁或以上女性中的成本-效果。本文对英国和美国的人口进行了分析。确诊的携带者接受降低风险的输卵管卵巢切除术。BRCA1/BRCA2/PALB2携带者可以选择核磁共振成像/乳房X光检查、化学预防或降低风险的乳房切除术。单向和概率敏感度分析(PSA)实现了模型不确定性评估。结果包括OC、BC和更多的心脏病死亡。计算质量调整生命年(QALYs)、OC发生率、BC发生率和增量成本效果比(ICER)。结果：与基于临床标准/FH的BRCA1/BRCA2检测相比，基于临床标准/FH的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2检测具有成本效益(ICER=7629.65磅/QALY或49 282.19美元/QALY；预期寿命增加0.04天)。与当前政策相比，基于人群的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2突变检测是最具成本效益的策略：ICER=E21 599.96/QALY或54 769.78美元/QALY(预期寿命增加9.34天或7.57天)。在3万英镑/QALY和10万美元/QALY的支付意愿阈值下，基于总体的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2面板测试在83.7%和92.7%的PSA模拟中是首选策略；在16.2%和5.8%的模拟中，基于标准/FH的面板测试是首选策略。基于人群的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2检测可以预防1.86%/1.91%的乳腺癌和3.2%/4.88%的OC，每百万人可预防657/655例OC和2420/2386例乳腺癌。结论：基于人群的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2检测比任何基于临床标准/FH的策略更具成本效益。基于临床标准/FH的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2检测比单独进行BRCA1/BRCA2检测更具成本效益。
Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women.Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (>= 10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer.Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = 7629.65 pound/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = E21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At 30 pound 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million.Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.