Table 4.

Signal detection methodologies and disproportionality statistics used to investigate signals of coronavirus disease 2019 (COVID-19) vaccine adverse events

	Method name	Description	Signal score computed
2 × 2 Disproportionality analysis	Multi-item Gamma Poisson Shrinker (MGPS)	Bayesian approach designed to guard against false positives due to multiple comparisons. Computes an adjusted value of the observed-to-expected reporting ratio corrected for temporal trends and confounding by age and sex. Bayesian prior parameters are estimated using Empirical Bayes	EBGM (Empirical Bayes Geometric Mean): a centrality measure of the posterior distribution of the true observed-to-expected in the population EB05/EB95: lower/upper 5th percentile of the posterior EBGM observed-to-expected distribution
	Proportional reporting ratio (PRR)	Method to compute a measure akin to relative risk to quantify the strength of association between a product and event. In its canonical version it does not correct for temporal trends and confounding by age and sex	PRR: point estimate (mean) of the relative risk reporting ratio distribution
	Bayesian Confidence Propagation Neural Network (BCPNN)	Originally inspired by neural networks, is a Bayesian approach for computing the observed-to-expected reporting ratio corrected for temporal trends and confounding by age and sex. Uses pre-specified Bayesian prior parameters. In practice, produces signal statistics close to those of MGPS	IC (Information Component): posterior mean of the log observed-to-expected ratio IC025/IC975: lower/upper bounds of the IC 95% confidence interval
Regression-based	Regression-Adjusted Gamma Poisson Shrinker (RGPS)	Use of Bayesian logistic regression to guard against masking effects and false signals due to confounding by concomitant products. Computes an adjusted value of the observed-to-expected reporting ratio that is corrected for temporal trends and confounding by age and sex	ERAM (Empirical-Bayes Regression-Adjusted Arithmetic Mean): posterior mean of the observed-to-expected distribution ER05/ER95: lower/upper 5th percentile of the posterior ERAM observed-to-expected distribution