【作者】 王洪涛；

【导师】 张新平；

【作者基本信息】 华中科技大学 ， 社会医学与卫生事业管理， 2013， 硕士

【摘要】 研究目的运用循证评价的方法对疏血通注射剂治疗脑梗死的有效性、安全性及经济性进行分析，为疏血通注射剂的临床推广应用、药物目录的科学遴选与调整提供证据支持。研究方法计算机检索Cochrane图书馆、PubMed数据库、CBM数据库、CNKI数据库、VIP全文数据库及万方数据库，收集所有关于疏血通注射剂治疗脑梗死的随机或半随机临床对照试验，根据偏倚风险评估条目评价所纳入文献的方法学质量，运用RevMan5.0软件对疏血通注射剂治疗脑梗死的有效性进行Meta分析；采用系统综述方法对疏血通注射剂治疗脑梗死的不良反应发生类型、原因等进行分析；运用药物经济学方法评价疏血通注射剂与其它治疗脑梗死药物经济性的优劣；基于系统评价与药物经济学评价的结果，运用GRADE系统对证据质量及推荐强度进行分析评价。研究结果1、本研究共纳入18篇文献，1962例患者，其中描述总有效率指标的文献有18篇，描述神经功能缺损评分与血液流变学指标的文献各10篇，描述不良反应情况的文献有17篇。2、在用药有效性方面，总有效率的Meta分析结果显示，疏血通注射剂优于对照组药物，且差异具有统计学意义[RR=1.17，95%CI（1.13，1.22），P<0.00001]；神经功能缺损评分的Meta分析结果显示，疏血通注射剂较对照组药物更能降低神经功能缺损评分值，且差异有统计学意义[WMD=-2.44，95%CI(-4.22，-0.65)，P=0.007]；血液流变学的Meta分析结果显示，疏血通注射剂在降低全血低切粘度[WMD=-2.09，95%CI(-3.28，-0.91)，P=0.0006]、全血高切粘度[WMD=-0.60，95%CI(-1.16，-0.04)，P=0.04]、红细胞聚集指数[WMD=-0.35，95%CI(-0.64，-0.05)，P=0.02]、血浆粘度[WMD=-0.23，95%CI(-0.33，-0.13)，P<0.00001]、纤维蛋白原[WMD=-0.78，95%CI(-1.24，-0.32)，P=0.0009]方面优于对照组药物，在降低红细胞压积[WMD=0.32，95%CI(-3.46，4.09)，P=0.87]方面与对照组药物相当。3、在用药安全性方面，系统综述结果显示，疏血通注射剂治疗脑梗死的不良反应较少，主要以过敏反应为主，但不良反应较为轻微。4、在用药经济性方面，选择纳入文献研究的四种较为常用的药物（疏血通注射剂，复方丹参注射剂、川芎嗪注射剂及血塞通注射剂）治疗方案进行经济性评价，成本效果分析结果显示，疏血通注射剂虽然药品成本较高，但其对脑梗死的治疗效果明显好于其他对照组药物，且多获得一个单位效果所需要花费的成本较少。5、本研究初步构建了药物目录遴选与调整的循证评价体系，GRADE证据级别及推荐强度结果显示，除总有效率指标的证据水平为中级外，其余有效性结局指标的证据质量均为低级，对疏血通注射剂的推荐强度结果为弱推荐。研究结论基于现有证据，疏血通注射剂治疗脑梗死在短期改善总有效率、降低神经功能缺损评分值及改善血液流变学等有效性指标方面好于对照组药物，安全性较好，是治疗脑梗死较为经济、合理的方案。但受到纳入文献质量的影响，疏血通注射剂治疗脑梗死的循证评价仍需更多高质量的随机临床对照试验资料给予支持，药物目录遴选与调整的循证评价体系也有待于进一步实践与完善。研究创新与不足之处1、本研究的创新点在于将系统评价中的风险偏倚评价工具、GRADE标准等较新成果及药物经济学评价方法运用于疏血通注射剂治疗脑梗死的循证评价过程中来，为我国开展药物目录遴选与调整工作提供了一种快速、方便、规范、可操作性较强的评价方法，逐步引导其由依赖专家的经验意见向依赖循证证据转变。2、本研究不足之处主要包括：（1）所纳入文献方法学质量总体较低，在一定程度上会影响到结果的可信度与论证强度；（2由于所纳入研究间存在方法学局限及异质性等原因，疏血通注射剂治疗脑梗死的证据质量相对较低；（3）部分结局指标纳入研究数量少，未能对其发表偏倚进行判断；（4）缺乏不良反应发生率等详细信息，未能对疏血通注射剂的安全性进行定量分析；（5）对疏血通注射剂的经济性评价缺乏原始成本数据支持，对分析结果有一定的影响。更多还原

【Abstract】 ObjectivesTo assess the efficacy, safety and economy of shuxuetong for cerebral infarctioncompared with open control or placebo. Through this study，it could provide evidence forclinical use of shuxuetong injection, selection and adjustment of drug list.MethodsRandomized controlled trails （RCTs） or quasi-randomized control trials onshuxuetong injection in the treatment of cerebral infarction were retrieved from theCochrane Library, PubMed, CBMdisc, CNKI, VIP and Wanfang database. Methodologicalquality evaluation was assessed by using risk of bias assessment tool. We conductedmeta-analysis to analyze the efficacy shuxuetong with the software RevMan5.0. Systematicreview method and cost-effectiveness analysis method were used to evaluate the adverseeffect and economy of shuxuetong injection respectively. We evaluated evidence quality degreeand strength of evidence recommendation by referring to GRADE system．Results1. This study included18randomized controlled trails, involving1962patients.18articles described total effective rate. The number of articles describing the neurologicaldeficit score, blood rheology indicators and adverse drug reaction was10,10and17respectively.2.Efficacy evaluation：The results of meta-analysis revealed that the difference of total effective rate (RR=1.17,95%CI:1.13to1.22, P<0.00001) and improvement of theneurological deficit (WMD=-2.44,95%CI:-4.22to-0.65, P=0.007) between shuxuetonginjection and control groups were statistically significant. Shuxuetong injection was betterthan the control groups in improving the low shear rate (WMD=-2.09,95%CI：-3.28to-0.91, P=0.0006) and high shear rate (WMD=-0.60,95%CI:-1.16to-0.04, P=0.04)ofwhole blood viscosity, erythrocyte aggregation index (WMD=-0.35,95%CI:-0.64to-0.05,P=0.02), plasma viscosity(WMD=-0.23,95%CI:-0.33to-0.13, P<0.00001) and plasmafibrinogen(WMD=-0.78,95%CI:-1.24to-0.32, P=0.0009), but hematocrit (WMD=0.32,95%CI:-3.46to4.09, P=0.87) had no statistical significance.3. Safety evaluation: The number of adverse drug reaction of shuxuetong injectionreported was small, and it was mainly allergic reaction and the symptom was not serious.4. Pharmacoeconomic evaluation was conducted among four drug treatment schedules,cost-effectiveness analysis results revealed that drug cost of shuxuetong injection was high,but its treatment effect of cerebral infarction was significantly better than drugs in thecontrol groups.5. In this study, we establish evidence-based evaluation system for the selection andadjustment of drug list initailly. Based on GRADE, the evidence quality degree of efficacyindicators was low or moderate, and the strength of evidence recommendation was weak．ConclusionsCurrent clinical evidences show that, compared with control groups, shuxuetonginjection is an effective, safe and economy drug schedule in treating patients with cerebralinfarction. Due to the low quality among the included studies, more high quality clinicaltrials are required.Innovation and drawbacks 1. The innovation point of this study was to conduct evidence-based evaluation ofshuxuetong injection in treatment of cerebral infarction by using the risk of bias assessmenttool, GRADE standard and cost-effectiveness analysis method, etc. Through this study，itcould provide a quick, convenient, standardized, strong operability evaluation method forselection and adjustment of drug list, and guide drug decision by relying on expert’sexperience to rely on evidence-based evidence.2. The shortcomings of this study included:(1) The methodological quality of theliteratures included was low and had an influence on the result credibility and strength ofevidence;(2)Due to methodological limitations and the heterogeneity, evidence quality ofshuxuetong injection was relatively low;(3) We did not judge publication bias of someindicators for the number of their literatures did not meet the requirements;(4) Quantitativeanalysis for safety of shuxuetong injection was not conducted for lack of detailedinformation of adverse reactions;(5) Pharmacoeconomic evaluation of to the shuxuetonginjection lacked original cost data, which will have a certain influence on analysis result.更多还原