Study on the risk signal mining related to letrozole based on the US Food and Drug Administration Adverse Event Reporting System
10.3760/cma.j.cn114015-20190910-00752
- VernacularTitle: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
- Author:
Li LI
1
;
Gen LI
;
Li CHEN
;
Liping WU
;
Wenmei GUO
;
Wanjun TAO
Author Information
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
- Publication Type:Journal Article
- Keywords:
Aromatase inhibitors;
Adverse drug reaction reporting systems;
United States Food and Drug Administration;
Signal processing, computer-assisted;
Letrozole
- From:
Adverse Drug Reactions Journal
2020;22(9):511-517
- CountryChina
- Language:Chinese
-
Abstract:
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 31 743 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 16 295 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 10 138 AE reports. The top 5 system organs in AE reports were neoplasms benign, malignant and unspecified (cysts and polyps) [24.48%(2 482/10 138)], musculoskeletal and connective tissue disorders [21.78%(2 208/10 138)], general disorders and administration site conditions [17.04%(1 728/10 138)], blood and lymphatic system disorders [17.04%(1 728/10 138)], 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 limit: 101.56], hashimoto′s encephalopathy[ ROR=164.85, 95 %CI lower limit: 69.68; PRR=142.51, 95 %CI lower limit: 67.74], and bone marrow oedema syndrome [ ROR=122.82, 95 %CI lower limit: 65.47; PRR=110.00, 95 %CI lower limit: 64.34]. Conclusions:Through data mining, 32 adverse reaction risk signals were found, which were not labelled in the drug instructions. Of them, ovarian fibrosis, ret gene mutation, antisynthetase syndrome, Hashimoto′s encephalopathy, and bone marrow oedema syndrome had strong signals, which were worthy of clinical attention.
