国家基本药物目录(2004年版)33种中药注射剂不良反应/不良事件文献分析

Adverse Drug Reactions and Adverse Events of 33 Varieties of Traditional Chinese Medicine Injections on the National Essential Drugs List(2004 edition) of China:An Overview on Published Literatures

目的了解国家基本药物目录(2004年版)33种中药注射剂不良反应/不良事件(ADR/AE)的基本情况和文献研究趋势,为中药注射剂研发、合理使用与安全警戒,以及风险管理工作提供参考依据。方法电子检索中国生物医学文献数据库(1978.1～2009.4)、中国期刊全文数据库(1979.1～2009.4)、中文科技期刊数据库(1989.1～2009.4)、中国中医药数据库(1984.1～2009.4)。同时检索卫生部及国家食品药品监督管理局(SFDA)网站,收集《药品不良反应信息通报》第1～22期中药注射剂ADR/AE相关信息。描述性分析我国中药注射剂ADR研究文献的发表时间、期刊和文献类型及出现ADR的中药注射剂和相应管理措施。结果①上述4个数据库共检出5405篇文献,剔除重复文献2160篇后,再按纳入与排除标准筛查文题、摘要和全文,最终纳入1010篇。②自1991年起,中药注射剂ADR年文献发表总量和年文献累积量均明显递增。③纳入的1010篇文献分布在297种期刊,其中55种药学类期刊共发表399篇(占文献总量的39.50%),64种中医、药类期刊共发表197篇(占19.50%),《中文核心期刊要目总览(2008年版)》医药卫生类收录的22种期刊共发表129篇(占12.77%)。④该1010篇文献分属8种类型,包括348篇个案报告(34.46%),254篇系列病例(25.15%),119篇综述(11.78%),116篇RCT(11.49%),78篇横断面研究(7.72%),61篇ADR文献分析(6.04%),28篇非随机对照试验(2.77%)。⑤《药物不良反应杂志》《、医药导报》和《中国药业》ADR文献发表量居297种期刊前三位(分别占5.84%、3.76%和2.67%)。⑥双黄连、清开灵和鱼腥草ADR报道最多,均超过200篇文献,占总文献的41.95%,国家卫生部和SFDA分别对其ADR进行管制。⑦双黄连、刺五加、鱼腥草和茵栀黄4种中药注射剂分别被撤市或叫停,其ADR文献发表量与监管作用相辅相成。结论①中药注射剂ADR研究呈增长态势,但总的数量少、发表分散、质量不高;②迫切需要研究制定中药注射剂ADR的分级和风险评价标准;③应有组织地推动中药注射剂安全性再评价和合理用药的宣传普及。

Objectives We conducted a literature review of 33 kinds of Traditional Chinese medicine injections（CMIs） on the national essential medicine list（2004 edition） of China in ADR articles to retrieve basic ADR information and research trends related to CMIs and to provide evidence for the research and development as well as the rational use of CMIs,particularly pharmacovigilance and risk management of CMIs.Methods We electronically searched Chinese Biomedical Literature Database（CBM,Jan.1978-April 2009）,the China National Knowledge Infrastructure Database（CNKI,Jan.1979-April 2009）,Chinese Science and Technology Periodical Database（VIP,Jan.1989-April 2009） and the Traditional Chinese Medicine Database（Jan.1984 April 2009）.We also retrieved the websites of Ministry of Health and State Food and Drug Administration,to collect data about CMIs ADRs reports and regulations from ＂Newsletter of Adverse Drug Reactions＂（Issue 1 to 22）.Then we descriptively analyzed all the results on the year published,periodicals and types of study design of included ADR literatures,the major CMIs as well as the regulations about their ADRs.Results（1） There were 5 405 citations found in total and 2160 were removed because of duplication.After screening the title,abstract and full text of the selected papers,1 010 studies nally met the eligible criteria.（2） The total and cumulative amount of research articles published about CMIs ADRs significantly increases over time.（3） The included 1,010 articles were scattered among 297 periodicals.A total of 55 journals on pharmaceutical medicine,containing 399 articles,accounted for 39.50% of total;64 journals on traditional Chinese medicine and pharmaceutical medicine,containing only 197 articles,amounted for 19.50% of total.Only 22 periodicals were included on the core journals of the Beijing University List（2008 edition）（8.94% of the total journals in the list）,which published 129 articles（12.77% of the total articles published）.（4） We categorized the articles included into eight categories based on their content and study methodology.There were：348 case reports and 254 case series which accounted for 34.46% and 25.15% of the total articles,119 overviews（11.78%）,116 randomized controlled trials（11.49%）,78 cross-sectional studies（7.72%）,61 ADR literature analyses（6.04%）,and 28 non-randomized controlled clinical studies（2.77%）.（5） In the three of top ten journals,＂Adverse Drug Reactions Journal＂,＂China Medical Herald＂,and ＂Chinese Pharmaceuticals＂ published literature accounted for 5.84%,3.76% and 2.67% of the total respectively.（6） The reports of ADRs to Shuanghuanglian,Qingkailing and Yuxingcao injections were the most in all reports for CMIs（All the three injections had more than 200 articles,accounting for 41.95% of the total）.The Ministry of Health and the State Food and Drug Administration took measures to supervise them.（7） The four kinds of CMIs（Shuanghuanglian,Ciwujia,Yuxingcao,and Yinzhihuang injections） among the top 5 reported ADR literatures were removed from the market or were suspended for sale.The varieties and numbers of reports for CMIs ADRs have relationship with the supervision to them.Conclusions（1） Articles published on CMIs ADRs increased year by year,but overall the research is of low quality and is scattered in a large number of sources.（2） It is very urgent to create a clear standard to grade ADRs of CMIs for the risk management.（3） It is necessary to enforce safety re-evaluation work for CMIs and to promote the clinical rational use.