Guzauskas Gregory F, Garbett Shawn, Zhou Zilu, Schildcrout Jonathan S, Graves John A, Williams Marc S, Hao Jing, Jones Laney K, Spencer Scott J, Jiang Shangqing, Veenstra David L, Peterson Josh F
The CHOICE Institute, Department of Pharmacy, University of Washington, Seattle, Washington (G.F.G., S.J.).
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee (S.G., J.S.S.).
Ann Intern Med. 2023 May;176(5):585-595. doi: 10.7326/M22-0846. Epub 2023 May 9.
The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.
To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).
Decision analytic Markov model.
Published literature.
Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.
Lifetime.
U.S. health care payer.
Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.
Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.
RESULTS OF BASE-CASE ANALYSIS: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).
Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.
Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.
Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.
National Human Genome Research Institute.
对美国人群进行疾病控制与预防中心（CDC）一级基因组疾病筛查的成本效益尚不清楚。
评估同时对林奇综合征（LS）、遗传性乳腺癌和卵巢癌综合征（HBOC）以及家族性高胆固醇血症（FH）进行基因组筛查的成本效益。
决策分析马尔可夫模型。
已发表的文献。
按年龄划分的不同队列（筛查时年龄为20至60岁），具有种族和民族代表性的美国成年人。
终生。
美国医疗保健支付方。
使用临床测序对一组有限的高证据基因进行人群基因组筛查，对一级亲属进行级联检测，并对确诊的先证者采取推荐的预防性干预措施。
乳腺癌、卵巢癌和结直肠癌发病病例；心血管事件发病情况；质量调整生存期；以及成本。
对100,000名未经筛选的30岁人群进行筛查，总体癌症病例减少了101例（95%不确定区间[UI]，77至127），心血管事件减少了15例（95% UI，4至28），质量调整生命年（QALY）增加了495个（95% UI，401至757），增量成本为3390万美元（95% UI，2700万美元至4110万美元）。每获得一个QALY的增量成本效益比为68,600美元（95% UI，41,800美元至88,900美元）。
在每QALY阈值为100,000美元的情况下，对30岁、40岁和50岁队列进行筛查在概率模拟中分别有99%、88%和19%具有成本效益。30岁、40岁和50岁人群达到每QALY阈值100,000美元时的检测成本分别为413美元、290美元和166美元。变异患病率和对预防性干预措施的依从性也是高度有影响的参数。
模型输入的人群平均值主要来自欧洲人群，在不同血统和医疗保健环境中存在差异。
如果检测成本相对较低且先证者能够获得预防性干预措施，对与3种CDC一级疾病相关的一组有限的高证据基因进行人群基因组筛查在美国40岁以下成年人中可能具有成本效益。
国家人类基因组研究所。
