华法令临床应用的质量控制与管理

发布时间：2018-04-18 03:18

本文选题：华法令 + 质量控制与管理　；参考：《天津大学》2014年博士论文

【摘要】：华法令作为目前应用最广的一线口服抗凝药，在临床应用中存在着很多局限性，主要表现为治疗窗较窄，剂量反应的个体差异较大以及严重的药物相互作用，被美国FDA列为不良反应发生率较高的十个药物之一。为减少其局限性，需要对其临床应用进行质量控制与管理。本课题确定了质量控制管理指标TTR，荟萃分析结果表明其与出血和血栓栓塞不良反应事件均存在负相关性。在此基础上，，提出了能够提升TTR的三个质量控制管理策略，包括抗凝门诊、患者自我监测与管理以及剂量模型的临床应用，并对剂量模型的临床应用进行了深入研究。首先，通过开展复方丹参滴丸-华法令药物相互作用临床试验研究搜集衍生集数据，构建了基于早期INR监测结果的剂量预测模型，并对模型进行整体适应性和有效性验证。验证结果表明，该模型的实际预测能力优于遗传剂量模型，可以解释86.8%的患者对华法令稳态剂量的个体差异，并且预测剂量的66.7%位于实际剂量±20%范围内。因此，早期的INR监测可以提供包括基因多态性和其他未知影响因素在内的综合信息，替代遗传基因信息反应患者对华法令的敏感性，提高剂量预测的准确性，在华法令临床应用中发挥重要的作用。在此基础上，应用决策树模型结合马尔科夫模型分别对INR剂量模型和遗传剂量模型进行成本-效用分析，为剂量模型在临床中的应用推广提供决策依据。分析结果表明，当TTR提升超过14.5%、INR超出疗效范围比例低于10.4%（TTR提升13.5%）或者CYP2C9和VKORC1基因类型的检测费用低于187.5美元/次（TTR提升13.5%，INR超出疗效范围为10.6%）时，遗传剂量模型才具有成本效用。而本课题建立的INR剂量模型只要较常规治疗对TTR有提升作用，便可在提高患者的质量生命调整年QALY的同时降低治疗费用，其在成本效用方面较遗传剂量模型具有显著的优势。本课题提出的华法令抗凝治疗的质量控制管理策略，特别是所建立的基于早期INR监测结果的INR剂量预测模型从抗凝治疗的有效性、安全性以及社会效益方面提升华法令临床应用的质量，为华法令临床应用的质量控制管理的前瞻性研究提供了决策依据。
[Abstract]:As the most widely used first-line oral anticoagulant, warfarin has many limitations in clinical application, such as narrow therapeutic window, large individual difference in dose response and severe drug interaction.It is listed as one of the ten drugs with high incidence of adverse reactions by FDA in the United States.In order to reduce its limitation, it is necessary to control and manage its clinical application.The quality control index TTRs were determined in this study. The results of meta-analysis showed that TTRs were negatively correlated with hemorrhage and adverse events of thromboembolism.On this basis, three quality control strategies to improve TTR are proposed, including anticoagulant clinic, patient self-monitoring and management, and clinical application of dose model.Firstly, a dose prediction model based on early monitoring results of INR was constructed by collecting derived data from the clinical trial of compound Danshen drop pill and warfarin drug interaction, and the overall adaptability and validity of the model were verified.The results show that the actual predictive ability of the model is better than that of the genetic dose model, which can explain the individual difference of the steady-state dose of warfarin in 86.8% of the patients, and 66.7% of the predicted dose lies within the range of 卤20% of the actual dose.Therefore, early INR surveillance can provide comprehensive information, including gene polymorphism and other unknown factors, to substitute the sensitivity of patients with genetic information response to warfarin and improve the accuracy of dose prediction.It plays an important role in the clinical application of propofol.On this basis, the cost-utility analysis of INR dose model and genetic dose model is carried out by using decision tree model and Markov model respectively, which provides the decision basis for the application and popularization of dose model in clinic.The results showed that the genetic dose model was cost-effective only when the proportion of TTR elevation over the therapeutic range was lower than that of 10.4%(TTR (13.5g) or the detection cost of CYP2C9 and VKORC1 gene types was less than $187.5 / time.As long as the dose model of INR can improve the quality of patients with TTR, it can reduce the cost of QALY while improving the quality of patients. It has a significant advantage over the genetic dose model in terms of cost utility.The quality control strategy of warfarin anticoagulant therapy proposed in this paper, especially the effectiveness of the established INR dose prediction model based on early INR monitoring results.Improving the quality of Warfarin clinical application in terms of safety and social benefits provides a basis for the prospective research on quality control management of Warfarin clinical application.
【学位授予单位】：天津大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R973

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