Abstract：
BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone.
METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated.
RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year\'s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths.
CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.
METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated.
RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year\'s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths.
CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.
摘要：
背景：对所有卵巢癌（OC）患者进行平行的种系和体细胞遗传测试，可以确定更多的致病变异（PV），这些变异将受益于PARP抑制剂（PARPi）治疗，并允许对未受影响的PVs亲属进行精确预防。在这项研究中,我们评估了英国和美国所有接受PARPi治疗的OC患者的平行小组种系和体细胞BRCA检测与基于临床标准/家族史(FH)的种系BRCA检测相比的成本-效果和人群影响.我们还评估了仅多基因组种系测试的成本效益。
方法：使用未选择的2,391（英国：n=1,483；美国：n=908）数据进行微观模拟成本效益建模，以人群为基础的OC患者用于比较所有OC病例(采用PARPi治疗)(策略A)和临床标准/以FH为基础的种系BRCA检测(策略B)的生存成本和效应.通过级联测试确定的生殖系BRCA1/BRCA2/RAD51C/RAD51D/BRIP1PV未受影响的亲属接受了适当的OC和乳腺癌（BC）风险降低干预措施。我们还比较了仅多基因组种系测试（不使用PARPi治疗）与策略B的成本效益。未受影响的PVs亲属可以接受降低风险的干预措施。具有付款人/社会观点的生命周期，连同概率/单向敏感性分析，被呈现。将获得的增量成本效益比（ICER）和每质量调整生命年的增量成本（QALY）与30,000英镑/QALY（英国）和100,000美元/QALY（美国）阈值进行比较。OC发生率,BC发病率,估计并防止了死亡。
结果：与临床标准/基于FH的BRCA测试相比，所有接受PARPi治疗的OC患者的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1种系测试和BRCA1/BRCA2体细胞测试的英国ICER为51,175英镑/QALY（付款人观点）和50,202英镑/QALY（社会观点），美国ICER为175,232美元/QALY（社会观点）和64,67美元在基本情况下，高于英国/NICE和美国的成本效益阈值。然而,如果PARPi费用降低45%~46%,或者PARPi的总生存率达到0.28的风险比,则策略A具有成本效益.单独进行未经选择的群体种系测试（不使用PARPi疗法）具有成本效益，付款人视角的ICER为11,291英镑/QALY或68,808美元/QALY，社会视角的ICER为6,923英镑/QALY或65,786美元/QALY。一年的检测可以预防209例英国BC/OC病例和192例死亡，560例美国BC/OC病例和460例死亡。
结论：未经选择的群体种系和体细胞BRCA测试可以具有成本效益，PARPi成本降低45%至46%。关于种系测试，未经选择的面板种系测试具有很高的成本效益，应取代BRCA单独测试。
方法：使用未选择的2,391（英国：n=1,483；美国：n=908）数据进行微观模拟成本效益建模，以人群为基础的OC患者用于比较所有OC病例(采用PARPi治疗)(策略A)和临床标准/以FH为基础的种系BRCA检测(策略B)的生存成本和效应.通过级联测试确定的生殖系BRCA1/BRCA2/RAD51C/RAD51D/BRIP1PV未受影响的亲属接受了适当的OC和乳腺癌（BC）风险降低干预措施。我们还比较了仅多基因组种系测试（不使用PARPi治疗）与策略B的成本效益。未受影响的PVs亲属可以接受降低风险的干预措施。具有付款人/社会观点的生命周期，连同概率/单向敏感性分析，被呈现。将获得的增量成本效益比（ICER）和每质量调整生命年的增量成本（QALY）与30,000英镑/QALY（英国）和100,000美元/QALY（美国）阈值进行比较。OC发生率,BC发病率,估计并防止了死亡。
结果：与临床标准/基于FH的BRCA测试相比，所有接受PARPi治疗的OC患者的BRCA1/BRCA2/RAD51C/RAD51D/BRIP1种系测试和BRCA1/BRCA2体细胞测试的英国ICER为51,175英镑/QALY（付款人观点）和50,202英镑/QALY（社会观点），美国ICER为175,232美元/QALY（社会观点）和64,67美元在基本情况下，高于英国/NICE和美国的成本效益阈值。然而,如果PARPi费用降低45%~46%,或者PARPi的总生存率达到0.28的风险比,则策略A具有成本效益.单独进行未经选择的群体种系测试（不使用PARPi疗法）具有成本效益，付款人视角的ICER为11,291英镑/QALY或68,808美元/QALY，社会视角的ICER为6,923英镑/QALY或65,786美元/QALY。一年的检测可以预防209例英国BC/OC病例和192例死亡，560例美国BC/OC病例和460例死亡。
结论：未经选择的群体种系和体细胞BRCA测试可以具有成本效益，PARPi成本降低45%至46%。关于种系测试，未经选择的面板种系测试具有很高的成本效益，应取代BRCA单独测试。
