Lacaze Paul, Marquina Clara, Tiller Jane, Brotchie Adam, Kang Yoon-Jung, Merritt Melissa A, Green Robert C, Watts Gerald F, Nowak Kristen J, Manchanda Ranjit, Canfell Karen, James Paul, Winship Ingrid, McNeil John J, Ademi Zanfina
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.
Health Economics and Policy Evaluation Research (HEPER) Group, Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
EClinicalMedicine. 2023 Nov 8;66:102297. doi: 10.1016/j.eclinm.2023.102297. eCollection 2023 Dec.
No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system.
This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18-40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100-$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis).
Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208).
Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration.
Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604).
此前尚无健康经济学评估，在国家公共医疗体系中，对成年人群进行多种高危疾病联合基因组筛查的影响和成本效益。
本模型研究评估了对澳大利亚所有年轻人进行遗传性乳腺癌和卵巢癌、林奇综合征和家族性高胆固醇血症联合基因组筛查的影响，并与当前针对每种疾病分别基于临床标准进行检测的做法进行比较。基因组筛查干预措施在首个年度模型周期中被视为一次性前期成本，可检测7个高危基因中的致病变异。模拟人群为18至40岁（共8324242人），从2023年起，每个样本检测成本在100澳元至1200澳元之间（基础情况为200澳元），检测接受率为50%。对已识别的高危变异携带者的干预遵循澳大利亚现行指南，模拟不完全接受和依从情况。从医疗系统和社会角度出发，结果指标为一生中因癌症（乳腺癌、卵巢癌、结直肠癌和子宫内膜癌）和冠心病（CHD）导致的发病率和死亡率。结果包括质量调整生命年（QALYs）和增量成本效益比（ICER），每年贴现5%（情景分析中贴现3%）。
在人群一生（至80岁）中，模型估计每10万人进行基因组筛查，通过预防63例癌症、31例冠心病病例和97例死亡可获得747个QALYs。在整个模型人群中，这意味着通过预防2612例癌症、542例非致命性冠心病事件和4047例总死亡可获得31094个QALYs。每次检测200澳元时，基因组筛查需要投资8.32亿澳元用于筛查50%的人群。我们的研究结果表明，从医疗系统角度来看，这种干预措施具有成本效益，相对于现状，每获得一个QALY的ICER为23926澳元（约合12050英镑/14110欧元/15345美元）。在贴现3%的情景分析中，ICER为4758澳元/QALY。基础情况的敏感性分析表明，联合基因组筛查在70%的模拟情况下具有成本效益，25%的情况下节省成本，5%的情况下不具有成本效益。阈值分析表明，在每次检测成本高达325澳元（约合164英镑/192欧元/208美元）时，基因组筛查在支付意愿阈值为50000澳元/QALY时具有成本效益。
我们的研究结果表明，在澳大利亚公共医疗体系中，以目前实际可行的检测成本，对年轻人进行高危疾病联合基因组筛查具有成本效益。其他事项，包括心理社会影响、伦理和社会问题以及实施挑战，也需要考虑。
澳大利亚政府卫生部、医学研究未来基金、基因组健康未来使命（APP2009024）。国家心脏基金会未来领袖奖学金（102604）。
