Jiang Shangqing, Guzauskas Gregory F, Garbett Shawn, Graves John A, Williams Marc S, Hao Jing, Zhu Jinyi, Jarvik Gail P, Carlson Josh J, Peterson Josh F, Veenstra David L
The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle, WA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN.
Genet Med. 2025 Feb;27(2):101285. doi: 10.1016/j.gim.2024.101285. Epub 2024 Sep 30.
Genomic screening to identify individuals with Lynch Syndrome (LS) and those with a high polygenic risk score (PRS) promises to personalize colorectal cancer (CRC) screening. Understanding its clinical and economic impact is needed to inform screening guidelines and reimbursement policies.
We developed a Markov model to simulate individuals over a lifetime. We compared LS+PRS genomic screening with standard of care (SOC) for a cohort of US adults at age 30. The Markov model included health states of no CRC, CRC stages (A-D), and death. We estimated incidence, mortality, and discounted economic outcomes of the population under different interventions.
Screening 1000 individuals for LS+PRS resulted in 1.36 fewer CRC cases and 0.65 fewer deaths compared with SOC. The incremental cost-effectiveness ratio was $124,415 per quality-adjusted life year; screening had a 69% probability of being cost-effective using a willingness-to-pay threshold of $150,000/quality-adjusted life year . Setting the PRS threshold at the 90th percentile of the LS+PRS screening program to define individuals at high risk was most likely to be cost-effective compared with 95th, 85th, and 80th percentiles.
Population-level LS+PRS screening is marginally cost-effective, and a threshold of 90th percentile is more likely to be cost-effective than other thresholds.
通过基因组筛查来识别林奇综合征（LS）患者和多基因风险评分（PRS）较高的个体，有望实现结直肠癌（CRC）筛查的个性化。需要了解其临床和经济影响，以为筛查指南和报销政策提供依据。
我们开发了一个马尔可夫模型来模拟个体一生的情况。我们将LS+PRS基因组筛查与30岁美国成年人群体的标准治疗（SOC）进行了比较。马尔可夫模型包括无CRC、CRC各阶段（A - D）以及死亡等健康状态。我们估计了不同干预措施下人群的发病率、死亡率和贴现后的经济结果。
与SOC相比，对1000名个体进行LS+PRS筛查可减少1.36例CRC病例和0.65例死亡。增量成本效益比为每质量调整生命年124,415美元；使用150,000美元/质量调整生命年的支付意愿阈值，筛查具有成本效益的概率为69%。与第95百分位、第85百分位和第80百分位相比，将PRS阈值设定在LS+PRS筛查项目的第90百分位以定义高危个体最有可能具有成本效益。
人群层面的LS+PRS筛查在成本效益上略显勉强，第90百分位的阈值比其他阈值更有可能具有成本效益。
