在意大利诊断为结直肠癌 (CRC) 的患者中进行了成本效用分析，以评估药物基因组学 (PGx) 指导的治疗与标准护理干预的比较。数据来源于前瞻性、开放标签、分组随机临床试验是全球最大的 PGx 研究（双臂 355 名患者）的一部分。死亡率被用作主要健康结果，以估计生存分析背景下治疗组获得的生命年 (LY)。 PGx 指导的治疗基于卡培他滨、5-氟尿嘧啶和伊立替康与 DPYD 和/或 UGT1A1 基因组变异之间已确定的药物基因相互作用。计算质量调整生命年 (QALY) 的效用值基于视觉模拟量表 (VAS) 评分。如果可能，通过多重插补方法和线性插值对缺失数据进行插补，同时通过“从右侧替换”算法对审查的成本数据进行纠正。计算 QALY 的增量成本效益比 (ICER)。原始数据被引导 5000 次，以便根据非参数百分位数方法产生 95% 的置信区间，并构建成本效益可接受性曲线。通过广义线性回归模型分析研究研究组的成本差异。每个患者的总治疗成本反映了管理任何不良事件所花费的所有资源，包括药物、诊断测试、设备、手术、重症监护病房和病房的使用。研究组的总成本估计为 380 欧元（ ～ 416 美元；95%CI：195-596）相比，对照组为 565 欧元（～ 655 美元；95%CI：340-724），而研究组的平均生存期估计为 1.58 ( 0.25) LYs 对比 1.50 ( 0.26)（对数秩检验，X2 = 4.219，df=1，p 值=0.04）。 QALY 未发现统计学上的显着差异。 ICER 估计为每个 QALY 13418 欧元（约 14695 美元），而可接受性曲线表明，当支付意愿低于 5000 欧元（约 5476 美元）时，PGx 具有成本效益的概率超过 70%。两组中最常见的药物不良事件是严重程度为 3 级和 4 级的中性粒细胞减少症，占研究组总事件的 82.6%，占对照组的 65.0%。除了研究组之外，吸烟状况、体重指数和累积可操作性也是总成本的重要预测因素。对可采取行动的患者（占患者总数的 7.9%）进行的亚组分析表明，PGx 指导的治疗是相对于其比较方案的主要选择，概率大于 92%。此外，还进行了一项重要的文献综述，这些发现与其他欧洲国家报告的结果一致。与欧洲结直肠癌患者管理的现有传统治疗方法相比，PGx 指导的治疗策略可能是一种节省成本的选择。意大利国家卫生服务中心。版权所有 © 2023 作者。由爱思唯尔有限公司出版。保留所有权利。

A cost-utility analysis was conducted to evaluate pharmacogenomic (PGx)-guided treatment compared to the standard-of-care intervention among patients diagnosed with colorectal cancer (CRC) in Italy.Data derived from a prospective, open-label, block randomized clinical trial, as a part of the largest PGx study worldwide (355 patients in both arms) were used. Mortality was used as the primary health outcome to estimate life years (LYs) gained in treatment arms within a survival analysis context. PGx-guided treatment was based on established drug-gene interactions between capecitabine, 5-fluorouracil and irinotecan with DPYD and/or UGT1A1 genomic variants. Utility values for the calculation of Quality Adjusted Life Year (QALY) was based on Visual Analog Scale (VAS) score. Missing data were imputed via the Multiple Imputation method and linear interpolation, when possible, while censored cost data were corrected via the Replace-From-The-Right algorithm. The Incremental Cost-Effectiveness Ratio (ICER) was calculated for QALYs. Raw data were bootstrapped 5000 times in order to produce 95% Confidence Intervals based on non-parametric percentile method and to construct a cost-effectiveness acceptability curve. Cost differences for study groups were investigated via a generalized linear regression model analysis. Total therapy cost per patient reflected all resources expended in the management of any adverse events, including medications, diagnostics tests, devices, surgeries, the utilization of intensive care units, and wards.The total cost of the study arm was estimated at €380 (∼ US$416; 95%CI: 195-596) compared to €565 (∼ US$655; 95%CI: 340-724) of control arm while the mean survival in study arm was estimated at 1.58 (+0.25) LYs vs 1.50 (+0.26) (Log Rank test, X2 = 4.219, df=1, p-value=0.04). No statistically significant difference was found in QALYs. ICER was estimated at €13418 (∼ US$14695) per QALY, while the acceptability curve indicated that when the willingness-to-pay was under €5000 (∼ US$5476), the probability of PGx being cost-effective overcame 70%. The most frequent adverse drug event in both groups was neutropenia of severity grade 3 and 4, accounting for 82.6% of total events in the study arm and 65.0% in the control arm. Apart from study arm, smoking status, Body-Mass-Index and Cumulative Actionability were also significant predictors of total cost. Subgroup analysis conducted in actionable patients (7.9% of total patients) indicated that PGx-guided treatment was a dominant option over its comparator with a probability greater than 92%. In addition, a critical literature review was conducted, and these findings are in line with those reported in other European countries.PGx-guided treatment strategy may represent a cost-saving option compared to the existing conventional therapeutic approach for colorectal cancer patient management in the National Health Service of Italy.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.