The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan

Rika Wakao, Ingrid M. Lönnstedt, Yasunori Aoki and Rebecca E. Chandler ()
Additional contact information
Rika Wakao: Pharmaceuticals and Medical Devices Agency (PMDA)
Ingrid M. Lönnstedt: Uppsala Monitoring Centre
Yasunori Aoki: Uppsala Monitoring Centre
Rebecca E. Chandler: Uppsala Monitoring Centre

Drug Safety, 2021, vol. 44, issue 6, No 7, 697 pages

Abstract: Abstract Introduction Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations. Objective The aim of this study was to explore the sensitivity of a global database of ICSRs to known pharmacogenomic risk variants common in Japan. Methods The data source was VigiBase, the global database of ICSRs, including all reports entered in the version frozen on 5 January 2020. Subgroup disproportionality analysis was used to compare ICSRs of two subgroups, Japan and rest of world (RoW). Reports for UGT1A1-metabolized irinotecan and the CYP2C19-metabolized drugs voriconazole, escitalopram and clopidogrel were selected for comparison between the subgroups based upon known genetic polymorphisms with high prevalence in Japan. Contrast between the subgroups was quantified by IC delta $$({\mathrm{IC}}_{\Delta }$$ ( IC Δ ), a robust shrinkage observed-to-expected (OE) ratio on a log scale. Harmonic mean p values (HMP) were calculated for each drug to evaluate whether a list of pre-specified ADRs were collectively significantly over- (or under-)reported as hypothesized. Daily drug dosages were calculated for ICSRs with sufficient information, and dose distributions were compared between Japan and RoW and related to differences in regionally approved doses. Results The predictions of over-reporting patterns for specific ADRs were observed and confirmed in bootstrap HMP analyses (p = 0.004 for irinotecan and p

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s40264-021-01063-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:spr:drugsa:v:44:y:2021:i:6:d:10.1007_s40264-021-01063-1

Ordering information: This journal article can be ordered from
http://www.springer.com/adis/journal/40264

DOI: 10.1007/s40264-021-01063-1

Access Statistics for this article

Drug Safety is currently edited by Nitin Joshi

More articles in Drug Safety from Springer
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().