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Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases.

Nomura K, Takahashi K, Hinomura Y, Kawaguchi G, Matsushita Y, Marui H, Anzai T, Hashiguchi M, Mochizuki M - Drug Des Devel Ther (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Proportion of suspected adverse events included in the reports for each MedDRA System Organ Class for 2010 in the USA and Japan.Abbreviations: JP, Japanese cases reported to the Japanese authority; F-JP, Japanese cases reported to the US authority; F-US, US cases reported to the US authority.
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f1-dddt-9-3031: Proportion of suspected adverse events included in the reports for each MedDRA System Organ Class for 2010 in the USA and Japan.Abbreviations: JP, Japanese cases reported to the Japanese authority; F-JP, Japanese cases reported to the US authority; F-US, US cases reported to the US authority.

Mentions: Table 3 shows an overview of AE reports in 2010 for comparison. Although the number of reported cases and primary suspected substances in the FAERS-JP was smaller than that in the JP, the number of reported AEs was larger, resulting in 1.6 and 3.3 AEs per case on average in the JP and FAERS-JP, respectively. The datasets provided roughly the same number of drug-event combinations at the preferred term level, while certain combinations showed different trends. AEs looked more severe in the JP for pyrexia, the most frequent AE in the FAERS-JP. Frequency of AEs at the MedDRA system organ class level differed between the JP and the FAERS-JP, for example, in “Blood and lymphatic system disorders”, “General disorders and administration site conditions”, and “Injury, poisoning and procedural complications” (Figure 1). Most of the Japanese cases (94.1% in the JP, 85.6% in the FAERS-JP) were medically confirmed, while consumers or lawyers initially reported one half of the FAERS-US cases. Although the JADER provides expedited reports, 6.2% of the FAERS-JP were periodic reports.


Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases.

Nomura K, Takahashi K, Hinomura Y, Kawaguchi G, Matsushita Y, Marui H, Anzai T, Hashiguchi M, Mochizuki M - Drug Des Devel Ther (2015)

Proportion of suspected adverse events included in the reports for each MedDRA System Organ Class for 2010 in the USA and Japan.Abbreviations: JP, Japanese cases reported to the Japanese authority; F-JP, Japanese cases reported to the US authority; F-US, US cases reported to the US authority.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472069&req=5

f1-dddt-9-3031: Proportion of suspected adverse events included in the reports for each MedDRA System Organ Class for 2010 in the USA and Japan.Abbreviations: JP, Japanese cases reported to the Japanese authority; F-JP, Japanese cases reported to the US authority; F-US, US cases reported to the US authority.
Mentions: Table 3 shows an overview of AE reports in 2010 for comparison. Although the number of reported cases and primary suspected substances in the FAERS-JP was smaller than that in the JP, the number of reported AEs was larger, resulting in 1.6 and 3.3 AEs per case on average in the JP and FAERS-JP, respectively. The datasets provided roughly the same number of drug-event combinations at the preferred term level, while certain combinations showed different trends. AEs looked more severe in the JP for pyrexia, the most frequent AE in the FAERS-JP. Frequency of AEs at the MedDRA system organ class level differed between the JP and the FAERS-JP, for example, in “Blood and lymphatic system disorders”, “General disorders and administration site conditions”, and “Injury, poisoning and procedural complications” (Figure 1). Most of the Japanese cases (94.1% in the JP, 85.6% in the FAERS-JP) were medically confirmed, while consumers or lawyers initially reported one half of the FAERS-US cases. Although the JADER provides expedited reports, 6.2% of the FAERS-JP were periodic reports.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus