Cost Effectiveness of Anticoagulation Versus Genetic Testing of CYP2C9 & VKORC1 G

描述（由申请方提供）：静脉血栓栓塞（VTE）的长期临床随访可能因发病率和死亡率过高而变得复杂。使用CYP 2C 9和VKORC 1基因检测来指导VTE患者的华法林给药，有可能降低抗凝过度和抗凝不足的发生率。然而，由于这项新技术的不确定性，目前还不清楚基因检测是否具有成本效益，因为干预费用增加。目的：本研究建议使用VTE自然史的模拟模型来确定CYP 2C 9和VKORC 1基因检测的成本效益，以从社会角度指导长期使用华法林抗凝治疗。方法学：将开发使用离散事件模拟的决策分析，以构建一个经济模型，描述疾病随时间演变的一组患者的健康状况。将记录并发症的相关成本和生活质量特征（效用）。数据将根据以下标准进行外推，包括患者年龄> 18岁、确诊的深静脉血栓形成或肺栓塞临床诊断、处方华法林治疗至少6个月以及目标INR在2至3之间的适应症。输入数据将从文献、HCUP-NIS、HCUP-SEDD和Medicare报销计划数据库中获得。将对所有参数进行敏感性分析，以解释模型中的不确定变量。主要和次要结局：将计算成本效益，以美元/质量调整生命年（$/QALY）衡量;并将衡量增量成本效益比。 公共卫生相关性：静脉血栓栓塞（VTE）是一种复杂的疾病，越来越多的患者面临着这种疾病，估计社区居民的发病率为每10000人年7例。华法林是治疗急性VTE发作和预防VTE复发的长期抗凝治疗的首选药物。然而，尽管对确诊患者进行密切监测以指导华法林给药，但在疾病的长期临床病程中，总体治疗管理仍存在许多严重挑战和不确定性（例如，医疗保健成本、华法林使用的结局）。由于华法林的治疗指数较窄，患者反应和治疗强度的个体间差异较大，华法林治疗的管理可能会增加出血（例如出血性卒中、死亡）或VTE复发（例如缺血性卒中）的风险。因此，在华法林给药前，建议对VKORC 1和CYP 2C 9基因进行基因检测，以确定与高国际标准化比值（INR）相关的基因型，并可能减少出血，以帮助降低风险获益比，优化患者的药物治疗，同时改善其结局和成本。本研究旨在评估基因检测的成本效益。

DESCRIPTION (provided by applicant): Long-term clinical follow-up of venous thromboembolism (VTE) can be complicated by excess morbidity and mortality. The use of genetic testing for the CYP2C9 and VKORC1 genes in order to guide warfarin dosing for patients with VTE holds significant promise potentially to reduce the incidence of over-and under anticoagulation. However, due to uncertainties regarding this new technology, it is unclear whether the genetic testing will be cost-effective given the increased cost of the intervention. Objective: This study proposes using a simulation model of the natural history of VTE to determine the cost-effectiveness of genetic testing for CYP2C9 and VKORC1 genes to guide long-term use of warfarin anticoagulation from the societal perspective. Methodology: A decision analysis using discrete event simulation will be developed to construct an economic model depicting the health states of a cohort of patients as the disease evolves over time. Associated costs and quality of life traits (utilities) of the complications will be captured. Data will be extrapolated with the criteria including patient age > 18 years, confirmed clinical diagnosis of deep venous thrombosis or pulmonary embolism, warfarin therapy prescribed for at least 6 months, and an indication for target INR between 2 to 3. Input data will be obtained from the literature, HCUP-NIS, HCUP-SEDD, and the Medicare Reimbursement Schedule database. Sensitivity analysis on all parameters will be performed to account for uncertainly variables in the model. Main and Secondary Outcomes: Cost-effectiveness, measured in dollars per quality adjusted life years gained ($/QALY) will be calculated; and the incremental cost effectiveness ratio will be measured. PUBLIC HEALTH RELEVANCE: Venous thromboembolism (VTE) is a complicated condition faced by an increasing number of patients and is estimated at an incidence of 7 per 10000 personyears among community residents. Warfarin is the drug of choice for long-term anticoagulation therapy for the treatment of acute VTE episode and the prevention of VTE recurrences. However, despite the close monitoring to guide warfarin dosing for diagnosed patients, overall treatment management still poses many serious challenges and uncertainties (e.g. healthcare cost, outcome of warfarin use) in the long term clinical course of the disease. Due to warfarin's narrow therapeutic index and wide inter-individual variability in patient response and intensity of the treatment, the management of warfarin therapy may increase the risk of bleeding (e.g. hemorrhagic stroke, death) or recurrences of VTE (e.g. ischemic stroke). Therefore, prior to warfarin administration, it has been proposed to conduct a genetic test for the VKORC1 and CYP2C9 genes to identify those genotypes associated with high International Normalize Ratio (INR) and presumably decrease bleeding to help decrease the risk-to-benefit-ratio, and optimize patients' drug therapy while improving their outcomes and costs. The current study is proposed to assess the cost-effectiveness of genetic testing for the identified genes.