药物不良反应信号检测

上海市ADR数据库中神经系统药物不良反应的信号检测发表时间：2009-9-18 9:37:29 来源：创新医学网推荐

刘媛1 程能能1? 杜文民2 王永铭1 (1 复旦大学药学院药理学教研室上海 200032; 2 上海市药品不良反应监测中心上海 200040)

LIU Yuan1, CHENG Neng-neng 1△ , DU Wen-ming2 , WANG Yong-ming1

(1 Department of Pharmacology, School of Pharmacy, Fudan University , Shanghai , 200032 ; 2 Shanghai Center f or Adverse Drug Reaction Monitoring, Shanghai , 200040 , China)

【摘要】背景在药品不良反应(ADR)监测数据库中存在大量已经明确因果关系的神经系统ADR报告,目前的ADR信号定量检测方法不区分数据库中的已知或未知报告。目的考察已知ADR报告对ADR信号检测效率的影响,并对上海市ADR数据库进行神经系统ADR信号检测。方法建立ADR信息库以自动判别ADR数据库中的已知ADR报告，采用PRR算法对上海市2004-2007年ADR自发呈报数据库进行信号检测，并计算可解释度以评价检出的信号。结果 1. 建立了包含1261种药物,4238种药物-事件组合 (drug-event combination, DEC)的神经系统ADR信息库；2.筛除已知ADR报告能提高神经系统ADR信号检出率24.64% ；3.检测计算共产生神经系统ADR信号98条，包括卡培他滨-咽下困难、吗替麦考酚酯-视觉异常、头孢他啶-精神病等值得关注的信号。结论筛除已知ADR报告能提高神经系统ADR信号的检测效率。

Abstract Background The signal detection for adverse drug reaction (ADR) is usually based on an ADR spontaneous reporting system (SRS) database containing a considerable proportion of known ADR reports. And currently no algorithm of signal detection can generate difference in results between the known and new ADR reports.

Purpose To examine the efficiency of ADR signal detection

based on SRS database while known ADR reports were excluded partially or totally and to identify potential ADR signals of nervous system.

Methods An ADR database of nervous system was established, which was used to remark known ADR reports from SRS automatically. ADR signals of nervous system were generated for possible hazards from proportional reporting ratios (PRR). A new measure representing the association between a drug and an AE was created and applied as reference to assist signal evaluation.

Results 1. An ADR database of nervous system containing 1261 drugs and 4138 DECs（Drug-effect combinations）was established. 2. Excluding the reports carrying only known ADRs from Shanghai SRS database above greatly improved the signal hit rate of nervous system by 24.64%.3. In total, 98 signals of nervous system were identified from Shanghai SRS database (during year 2004-2007), including Capecitabine-induced dysphagia, Mycophenolatemofetil–induced vision abnormal and ceftazidime–induced phycosis. Conclusions Excluding the reports carrying only known ADRs can improve the efficiency of ADR signal detection of nervous system.

一、背景

WHO对药品不良反应(adverse drug reactions , ADRs)的定义是：在正常用量和用法情况下，药物在预防、诊断、治疗疾病或调节生理功能时所发生意外的、与防治目的无关的不利或有害的反应。当前，随着临床用药数量及品种的大幅增加，药物ADR的发生数量也持续上升，由药物ADR产生的药源性疾病已成为全球主要疾病之一。在所有药物ADR中，发生在神经系统的毒副作用占24.8 - 26.8%[1]，显著高于其它系统或组织。目前已知的引起神经系统ADR的常见药物就达40余种，其中以抗感染药物为主，尤以喹诺酮类和β-内酰胺类最为多见[2]。

药品不良反应(ADR)自发呈报系统(spontaneous reporting system, SRS)是目前世界上最主要的ADR监测手段,也是目前发现ADR信号的最主要来源。目前全球范围内尚无利用数据挖掘技术，通过ADR自发呈报库数据来探索未