title: Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases.
abstract: BACKGROUND
  The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection.
  
  
  METHODS
  Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems.
  
  
  RESULTS
  The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected.
  
  
  CONCLUSIONS
  The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Japan Pharmaceutical Information Center, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hinomura
authors.affiliation: Global Pharmacovigilance, Kissei Pharmaceutical Co Ltd, Tokyo, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Kawaguchi
authors.affiliation: Medical Affairs Department, Daiichi Sankyo Co Ltd, Keio University, Tokyo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Drug Safety Division, Chugai Pharmaceutical Co Ltd, Keio University, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Marui
authors.affiliation: Data Science Center, EPS Corporation, Keio University, Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Anzai
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashiguchi
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D001499:Bayes Theorem; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D000068800:Etanercept / Q000009:adverse effects; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects; D007564:Japan / Q000453:epidemiology; D016571:Neural Networks, Computer; D016017:Odds Ratio; D017374:Paroxetine / Q000009:adverse effects; D016012:Poisson Distribution; D012449:Safety; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D017374:Paroxetine; D000069285:Infliximab; D000068800:Etanercept
keywords: Japan; drug safety; reporting disproportionality; spontaneous reports system