基于美国FDA不良事件报告系统数据库的来曲唑风险信号挖掘  

Study on the risk signal mining related to letrozole based on the US Food and Drug Administration Adverse Event Reporting System

作　　者：李莉 李根 陈力[2] 伍丽萍 郭文玫 陶婉君 Li Li;Li Gen;Chen Li;Wu Liping;Guo Wenmei;Tao Wanjun(Chengdu Women′s and Children′s Central Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 611731,China;Department of Pharmacy,West China Second University Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]电子科技大学医学院附属妇女儿童医院·成都市妇女儿童中心医院药学部,成都611731 [2]四川大学华西第二医院药学部,成都610041

出　　处：《药物不良反应杂志》2020年第9期511-517,共7页Adverse Drug Reactions Journal

基　　金：四川省科学技术厅软科学研究项目(2019JDR0163)。

摘　　要：目的挖掘来曲唑相关不良反应风险信号,为该药临床安全应用提供参考。方法利用报告比值比(ROR)法和比例报告比值比(PRR)法对美国FDA不良事件报告系统(FAERS)中2009年第1季度至2019年第1季度的不良事件(AE)报告中来曲唑相关不良反应风险信号进行挖掘。AE报告数>3且ROR和PRR的95%置信区间(CI)下限>1的AE被定义为阳性信号。采用国际医学用语词典(MedDRA)的首选系统器官分类(SOC)和首选术语(PT)对AE进行统计和分类,选取AE报告数和信号强度排名前50位的PT进行分析。结果设定时段内FAERS数据库共收到以来曲唑为首要可疑药物的AE报告31743例,检测出报告数>3且ROR和PRR的95%CI下限>1的AE风险信号483个,涉及AE报告16295例。经第2次筛选,获得AE报告数排名前50位和ROR值的排名前50位的PT,筛重后纳入分析的PT为93个,涉及AE报告10138例。AE报告数居前5位的系统器官依次为良性、恶性及性质不明的肿瘤(包括囊状和息肉状)[24.48%(2482/10138)]、各种肌肉骨骼及结缔组织疾病[21.78%(2208/10138)]、全身性疾病及给药部位各种反应[17.04%(1728/10138)]、血液及淋巴系统疾病[8.82%(894/10138)]和各类检查[5.47%(555/10138)]。药品说明书中未收录的PT有32个,信号强度排名前5位者依次为卵巢纤维化(ROR=379.63,95%CI下限:120.87;PRR=278.66,95%CI下限:120.39)、ret基因突变(ROR=379.63,95%CI下限:120.87;PRR=278.66,95%CI下限:120.39)、抗合成酶抗体综合征[ROR=208.84,95%CI下限:190.30;PRR=174.20,95%CI下限:101.56]、桥本脑病[ROR=164.85,95%CI下限:69.68;PRR=142.51,95%CI下限:67.74]和骨髓水肿综合征[ROR=122.82,95%CI下限:65.47;PRR=110.00,95%CI下限:64.34]。结论挖掘出32个来曲唑说明书中未收录的不良反应风险信号,其中以卵巢纤维化、ret基因突变、抗合成酶抗体综合征、桥本脑病和骨髓水肿综合征信号较强,值得临床关注。Objective To explore the risk signals of letrozole related adverse reactions and provide reference for the clinical safety of letrozole.Methods The risk signals related to letrozole in the adverse events(AEs)reports from the first quarter of 2009 to the first quarter of 2019 in the US FDA adverse event reporting system(FAERS)were mined using the reporting odds ratio(ROR)method and the proportional reporting odds ratio(PRR)method.An AE with reports>3 and 95%confidence interval(CI)lower limit of ROR and PRR>1 was defined as a positive signal.AEs were counted and classified using the preferred system organ class(SOC)and preferred term(PT)of Medical Dictionary for Regulatory Activities(MedDRA).The PTs of top 50 adverse event reports and signal strength were selected and analyzed.Results From the first quarter of 2009 to the first quarter of 2019,a total of 31743 AE reports with letrozole as the primary suspicious drug were reported in the FAERS database.Four hundred and eighty⁃three AE risk signals with reports>3 and the 95%CI lower limit of ROR and PRR>1 were detected,involving 16295 AE reports.After the second screening,PTs with the top 50 AE reports and those with the top 50 PTs ROR values were obtained.After screening out repeated PTs,93 PTs were included in the analysis,involving 10138 AE reports.The top 5 system organs in AE reports were neoplasms benign,malignant and unspecified(cysts and polyps)[24.48%(2482/10138)],musculoskeletal and connective tissue disorders[21.78%(2208/10138)],general disorders and administration site conditions[17.04%(1728/10138)],blood and lymphatic system disorders[17.04%(1728/10138)],and investigations[5.47%(555/10138)].There were 32 PTs not labelled in the drug instructions,and PTs with the top 5 signal strength were ovarian fibrosis[ROR=379.63,95%CI lower limit:120.87;PRR=278.66,95%CI lower limit:120.39],ret gene mutation[ROR=379.63,95%CI lower limit:120.87;PRR=278.66,95%CI lower limit:120.39],antisynthetase syndrome[ROR=208.84,95%CI lower limit:190.30);PRR=174.20,95%CI lower lim

关 键 词：芳香酶抑制剂 药物不良反应报告系统 美国食品和药物管理局 信号处理 计算机辅助 来曲唑 

分 类 号：R969[医药卫生—药理学]