Signal Detection of Potentially Drug-Induced Acute Liver Injury in Children Using a Multi-Country Healthcare Database Network

被引:27
作者
Ferrajolo, Carmen [1 ,2 ]
Coloma, Preciosa M. [1 ]
Verhamme, Katia M. C. [1 ]
Schuemie, Martijn J. [1 ]
de Bie, Sandra [1 ]
Gini, Rosa [3 ]
Herings, Ron [4 ]
Mazzaglia, Giampiero [5 ]
Picelli, Gino [6 ]
Giaquinto, Carlo [7 ]
Scotti, Lorenza [8 ]
Avillach, Paul [9 ]
Pedersen, Lars [10 ]
Rossi, Francesco [2 ]
Capuano, Annalisa [2 ]
van der Lei, Johan [1 ]
Trifiro, Gianluca [1 ,11 ]
Sturkenboom, Miriam C. J. M. [1 ,12 ]
机构
[1] Erasmus MC, Dept Med Informat, NL-3015 GE Rotterdam, Netherlands
[2] Univ Naples 2, Pharmacol Sect, Dept Expt Med, Campania Reg Ctr Pharmacovigilance Pharmacoepidem, I-80138 Naples, Italy
[3] Reg Hlth Agcy Tuscany, Florence, Italy
[4] PHARMO Inst, Utrecht, Netherlands
[5] Italian Coll Gen Practitioners, Florence, Italy
[6] Pedianet Soc Serv Telematici SRL, Padua, Italy
[7] Univ Hosp Padua, Dept Paediat, Padua, Italy
[8] Univ Milano Bicocca, Dept Stat & Quantitat Methods, Milan, Italy
[9] Univ Bordeaux 2, ISPED, LESIM, F-33076 Bordeaux, France
[10] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark
[11] Univ Messina, Dept Clin & Expt Med, Messina, Italy
[12] Erasmus MC, Rotterdam, Netherlands
关键词
8 PATIENT DATABASES; HOMOGENEOUS IDENTIFICATION; INHALED CORTICOSTEROIDS; SEMANTIC APPROACH; EVENTS; ASSOCIATION; HEPATITIS; DESIGN;
D O I
10.1007/s40264-013-0132-9
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Background Data mining in spontaneous reporting databases has shown that drug-induced liver injury is infrequently reported in children. Objectives Our objectives were to (i) identify drugs potentially associated with acute liver injury (ALI) in children and adolescents using electronic healthcare record (EHR) data; and (ii) to evaluate the significance and novelty of these associations. Methods We identified potential cases of ALI during exposure to any prescribed/dispensed drug for individuals <18 years old from the EU-ADR network, which includes seven databases from three countries, covering the years 1996-2010. Several new methods for signal detection were applied to identify all statistically significant associations between drugs and ALI. A drug was considered statistically significantly associated with ALI, using all other time as a reference category, if the 95 % CI lower band of the relative risk was >1 and in the presence of at least three exposed cases of ALI. Potentially new signals were distinguished from already known associations concerning ALI (whether in adults and/or in the paediatric population) through manual review of published literature and drug product labels. Results The study population comprised 4,838,146 individuals aged < 18 years, who contributed an overall 25,575,132 person-years of follow-up. Within this population, we identified 1,015 potential cases of ALI. Overall, 20 positive drug-ALI associations were detected. The associations between ALI and domperidone, flunisolide and human insulin were considered as potentially new signals. Citalopram and cetirizine have been previously described as hepatotoxic in adults but not in children, while all remaining associations were already known in both adults and children. Conclusions Data mining of multiple EHR databases for signal detection confirmed known associations between ALI and several drugs, and identified some potentially new signals in children that require further investigation through formal epidemiologic studies. This study shows that EHRs may complement traditional spontaneous reporting systems for signal detection and strengthening.
引用
收藏
页码:99 / 108
页数:10
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