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

描述(由申请人提供)：静脉血栓栓塞症(VTE)的长期临床随访可能会因发病率和死亡率过高而复杂化。使用对CYP2C9和VKORC1基因的基因检测来指导静脉血栓栓塞症患者华法林剂量的使用，有可能减少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，鉴于干预成本的增加，目前尚不清楚基因检测是否具有成本效益。目的：本研究建议使用静脉血栓栓塞症自然病史的模拟模型来确定CYP2C9和VKORC1基因检测的成本-效果，以从社会角度指导华法林抗凝的长期使用。方法：将开发一个使用离散事件模拟的决策分析，以构建一个经济模型，描述随着疾病随着时间的推移而演变的一群患者的健康状况。相关费用和并发症的生活质量特征(公用事业)将被捕获。数据将根据患者年龄和18岁、确诊的深静脉血栓形成或肺栓塞的临床诊断、至少6个月的华法林治疗处方以及目标INR在2至3之间的适应症进行推断。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，以考虑模型中的不确定变量。主要和次要结果：将计算成本效益，以每获得质量调整寿命年(美元/QALY)的美元衡量；并将衡量增量成本效益比率。 公共卫生相关性：静脉血栓栓塞症是越来越多的患者面临的一种复杂疾病，估计在社区居民中每10000人年中有7人发生。华法林是治疗VTE急性发作和预防VTE复发的长期抗凝治疗的首选药物。然而，尽管有密切的监测来指导确诊患者的华法林剂量，但在疾病的长期临床过程中，整体治疗管理仍然带来许多严重的挑战和不确定因素(如医疗成本、华法林使用的结果)。由于华法林的治疗指数较窄，患者反应和治疗强度的个体差异很大，华法林治疗的管理可能会增加出血(如出血性中风、死亡)或VTE复发(如缺血性中风)的风险。因此，在服用华法林之前，有人建议对VKORC1和CYP2C9基因进行基因测试，以确定那些与高国际正常化比率(INR)相关的基因类型，并可能减少出血，以帮助降低风险-收益比，并在改善患者结果和成本的同时优化患者的药物治疗。目前的研究是为了评估对已识别基因进行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.