Table 5.
Concepts and conditions used to evaluate signals
| Concept | Definition |
|---|---|
| Signaling threshold | A cutoff value for a given signal score (association statistic) that is used to decide if a signal is present or absent. This investigation uses the value 1.0 (or 0.0 on the log scale), which for association statistics derived from ratios corresponds to the boundary of no statistical association |
| Signal present | For a given AE and signal score, a signal is present (i.e., detected) if a positive statistical association for the AE is identified. This occurs when the signal score for the AE (or its lower interval limit) exceeds the signaling threshold. This investigation requires that the lower limit of the signal score’s credible interval exceeds the signaling threshold, e.g., ER05 > 1.0 for RGPS and EB05 > 1.0 for MGPS |
| Signal absent | For a given AE and signal core, a signal is absent (not detected) if the signal score’s credible interval contains or falls below the signaling threshold, e.g., ER05 < 1.0 for RGPS and EB05 < 1.0 for MGPS |
| Statistically significant signal score difference | For a given association, the difference between two signal scores computed by two different methodologies is statistically significant if their credible intervals do not overlap. Likewise, we say that there is no difference in signal scores if their credible intervals overlap, e.g., ER05 < EB95 < ER95 |
| Candidate association for masking |
Candidate associations for masking are identified as those whose signal statistics satisfy the following condition: ER05 > EB95 and ER05 > 1 and EB05 ≤ 1 That is, an association where RGPS and MGPS disagree by producing signal scores that are statistically significant (non-overlapping credible intervals, ER05 > EB95) with RGPS’s interval above the signaling threshold (ER05 > 1) and that of MGPS below or including the threshold (EB05 ≤ 1) |
| Masking effect size |
The masking effect size is defined by the ratio of RGPS’s and MGPS’s signal scores, i.e.,
In this investigation, the masking effect size will be averaged across the time series to produce a summary statistic and represented as a percentage |
AE adverse event, EBGM Empirical Bayes Geometric Mean, ERAM Empirical-Bayes Regression-Adjusted Arithmetic Mean, MGPS Multi-item Gamma Poisson Shrinker, RGPS Regression-Adjusted Gamma Poisson Shrinker