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. 2021 Sep 22;13(10):1531.
doi: 10.3390/pharmaceutics13101531.

Verification of the "Upward Variation in the Reporting Odds Ratio Scores" to Detect the Signals of Drug-Drug Interactions

Yoshihiro Noguchi  1 , Shunsuke Yoshizawa  1 , Keisuke Aoyama  1 , Satoaki Kubo  1 , Tomoya Tachi  1 , Hitomi Teramachi  1
Affiliations

Verification of the "Upward Variation in the Reporting Odds Ratio Scores" to Detect the Signals of Drug-Drug Interactions

Yoshihiro Noguchi et al. Pharmaceutics. .

Abstract

The reporting odds ratio (ROR) is easy to calculate, and there have been several examples of its use because of its potential to speed up the detection of drug-drug interaction signals by using the "upward variation of ROR score". However, since the validity of the detection method is unknown, this study followed previous studies to investigate the detection trend. The statistics models (the Ω shrinkage measure and the "upward variation of ROR score") were compared using the verification dataset created from the Japanese Adverse Drug Event Report database (JADER). The drugs registered as "suspect drugs" in the verification dataset were considered as the drugs to be investigated, and the target adverse event in this study was Stevens-Johnson syndrome (SJS), as in previous studies. Of 3924 pairs that reported SJS, the number of positive signals detected by the Ω shrinkage measure and the "upward variation of ROR score" (Model 1, the Susuta Model, and Model 2) was 712, 2112, 1758, and 637, respectively. Furthermore, 1239 positive signals were detected when the Haldane-Anscombe 1/2 correction was applied to Model 2, the statistical model that showed the most conservative detection trend. This result indicated the instability of the positive signal detected in Model 2. The ROR scores based on the frequency-based statistics are easily inflated; thus, the use of the "upward variation of ROR scores" to search for drug-drug interaction signals increases the likelihood of false-positive signal detection. Consequently, the active use of the "upward variation of ROR scores" is not recommended, despite the existence of the Ω shrinkage measure, which shows a conservative detection trend.

Keywords: drug–drug interaction; reporting odds ratio (ROR); spontaneous reporting systems; Ω shrinkage measure.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The association between the ROR score ratio (Model 1, Susuta model) and disproportionality score.
Figure 2
Figure 2
The association between the ROR score ratio (Model 2) and disproportionality score.
Figure 3
Figure 3
Relationship between the number of reports (N11 [= n111]), RORdrug D1 ∩ drug D2, and ROR score ratio (Model 1).
See this image and copyright information in PMC

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