银杏内酯注射液治疗脑梗死的临床综合评价

Clinical comprehensive evaluation of Ginkgolide Injection in treatment of cerebral infarction

该研究以药品临床价值为导向,依据《药品临床综合评价管理指南(2021年版试行)》开展的药品临床综合评价,采用定性与定量相结合的评价方法,基于循证医学、流行病学、临床医学、药物经济学、数理统计学、卫生技术评估(HTA)等,通过专家对准则层、指标层赋予权重,采用多准则决策分析(MCDA)模型及CSC v2.0软件进行计算,从“6+1”维度评估银杏内酯注射液的临床价值。银杏内酯注射液上市后开展了Ⅳ期临床试验、自发呈报系统(SRS)监测数据、系统评价和Meta分析、急性毒性和长期毒性实验、主动监测和RCT研究,安全性研究证据充分。主动监测研究结果显示不良反应发生率为0.09%(属罕见),不良反应临床表现为潮红、头晕、皮疹、恶心、呕吐等,经巢式病例对照研究分析,药品不良反应与产品批次无关,即药品质量可控;主要以药物的药效学反应为主,因该药可抗血小板聚集,因此会出现血管扩张而引起的潮红、头晕、头痛、静脉炎等药效学不良反应症状,而皮疹及消化道症状更多考虑患者对药物的敏感性和自身过敏体质。根据该品安全性研究证据充分性与不良反应发生率,安全性评为A级。Meta分析结果表明,银杏内酯注射液联合西医常规治疗在改善脑梗死患者临床有效率、神经功能评分、日常生活活动能力评分方面优于单用西医常规治疗,按照PICO原则评价有效性证据价值较高;根据GREAD评价原则,对临床有效率、美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(简称BI)评定量表进行证据质量评价,结果在临床有效率和BI评定量表证据质量等级为中等,有效性为A级。根据银杏内酯注射液已开展的经济学报告,该药治疗缺血性脑卒中具有短期和长期的药物经济学优势,经济性证据价值较好,根据CASP清单评价原则,经济学报告的总体质量评价结果基本明确,经济性证据质量较高,综合证据质量和经济价值,经济性评为A级。创新性从临床创新性、企业服务体系创新性和产业创新性3个方面评价,由于银杏内酯注射液可以在静脉溶栓后24 h内使用,不增加出血的同时还可以改善患者的神经功能,解决了用药盲区,具有重要的临床创新性;在保证药品供应,保障基层配备,保障药品安全、有效、价格合理方面多有创新;在企业理念、药装资源管理、工艺和科技研发、企业管理和市场营销方向也有借鉴之处,因此创新性评为A级。该药在使用中无特殊用药方案,对医生、护士及患者适宜性较好,适宜性评为B级。与同类药品相比,药品价格一般,处于中等水平,可负担性较好,其产能充足,可获得性好,可及性评为B级。该药属中药注射剂类别,开展了大样本的真实世界研究,人用经验较丰富,中医药特色评为C级。综合评价银杏内酯注射液治疗脑梗死临床价值为A类,建议可按程序转化为基本临床用药管理的相关政策结果。

This clinical value-oriented comprehensive evaluation of drugs was carried out in accordance with Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021),with the qualitative and quantitative evaluation methods adopted.Based on the evidence-based medicine,epidemiology,clinical medicine,pharmacoeconomics,mathematical statistics,and health technology evaluation(HTA),the clinical value of Ginkgolide Injection was evaluated from the"6+1"dimension by giving weight to the criterion level and index level and calculating with multi-criteria decision analysis(MCDA)model and CSC v2.0.After entering the market,Ginkgolide Injection has been subjected to phaseⅣclinical trial,spontaneous reporting system(SRS)-based data monitoring,systematic review and Meta-analysis,acute toxicity and long-term toxicity assays,active monitoring,and RCTs,and the evidence of safety was sufficient.The results of active monitoring showed that the incidence of adverse reactions was 0.09%(rare),mainly manifested as flushing,dizziness,rash,nausea,and vomiting.According to the nested case-control study,the adverse reactions of this drug had nothing to do with the product batch,implying that the drug quality was controllable.The adverse reactions mainly resulted from the pharmacodynamic reactions.Because the drug was effective in resisting platelet aggregation,the resulting adverse reactions such as flushing,dizziness,headache,and phlebitis were caused by vasodilation.Skin rash and gastrointestinal symptoms were mainly attributed to the patients′sensitivity to drugs and their own allergic constitution.According to the sufficiency of evidence and the incidence of adverse reactions in the safety research,the safety of Ginkgolide Injection was grade A.The results of Meta-analysis showed that Ginkgolide Injection combined with conventional western medicine was superior to conventional western medicine in improving the clinical effective rate,neurological function score,and activity of daily living score of patients with cerebral infarction.The validity evidence was evaluated according to the PICO principle to be high.According to the GREAD evaluation principle,the quality of such evidence as clinical effective rate,National Institute of Health stroke scale(NIHSS),and Barthel Index(BI)was evaluated,and the results demonstrated that the evidence quality of clinical effective rate and activity of daily living score was medium.The effectiveness of Ginkgolide Injection was grade A.According to the economic report of Ginkgolide Injection,it had short-term and long-term pharmacoeconomic advantages in the treatment of ischemic stroke,and the economic evidence value was good.According to the CASP economic evaluation checklist,the overall quality evaluation results of the economic report are basically clear.To be specific,the economic evidence quality was high.Based on the comprehensive economic evidence quality and economic value,the economy of this drug was grade A.The innovation of this product was evaluated from three aspects:clinical innovation,enterprise service system innovation,and industrial innovation.Ginkgolide Injection could be used 24 h after intravenous thrombolysis for improving patients′neurological function without increasing bleeding,indicating its important clinical innovation.There were many innovations in ensuring drug supply,especially at the grass roots,drug safety,effectiveness,and reasonable price,which has provided reference for establishing enterprise philosophy,managing drug resources,developing process and technology,and determining enterprise management and marketing.Therefore,its innovation was grade A.The drug had no special medication plan in use,exhibiting good suitability for doctors,nurses,and patients.The suitability was grade B.Compared with similar drugs,its price was at a medium level,meaning good affordability,sufficient production capacity,and easy accessibility.Its accessibility was therefore grade B.This drug belonged to Chinese medicinal injection.The large-sample real-world research revealed rich human use experience,so it was grade C for the traditional Chinese medicine characteristic.According to the comprehensive evaluation,the clinical value of Ginkgolide Injection in the treatment of cerebral infarction fell into class A.It is suggested that it can be transformed into the relevant policy results of basic clinical medication management according to the procedure.