DARE-SAFE: Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation in Pharmaceuticals and Vaccines

Background/Objectives: Controversy exists over the use of passive reporting systems, especially the Vaccine Adverse Event Reporting System, in risk assessment. One limitation of these systems is that adverse event (AE) reporting rates cannot be calculated without knowing the number of shots administered or prescriptions in the case of pharmaceuticals. Adverse event reporting rates can be a factor in a risk assessment, though they should not be solely relied on; they can be used to compare the relative safety profiles of different vaccine products or pharmaceuticals. This study introduces the Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation (DARE-SAFE) method to analyze pharmacovigilance reporting rates for vaccines and common pharmaceuticals. Methods: We calculated reporting rates for the top 250 most prescribed drugs in the US Food and Drug Association (FDA) Adverse Event Reporting System and common vaccines in the Vaccine Adverse Events Reporting System. For vaccines, we used USA Centers for Disease Control (CDC) dose data and OpenVAERS reports. For pharmaceuticals, we utilized prescription data from ClinCalc and FAERS reports for 2022. Results: VAERS reporting rates varied significantly across vaccine types. COVID-19 vaccines showed a 63.0 ± 0.6 times higher rate of VAERS deaths per dose and an 18.95 ± 0.02 times higher rate of total adverse event reports per dose compared to influenza vaccines. The ratio of total VAERS reports to deaths for vaccines was 73 ± 4 to 1 (R2 = 0.94). For pharmaceuticals, the ratio of total adverse event reports to deaths was 26 ± 2 (R2 = 0.46), with a strong correlation between serious adverse events and deaths (ratio 9.1 ± 0.3, R2 = 0.79). Conclusions: DARE-SAFE provides a standardized method for comparing reporting rates across different medical products. The observed differences between vaccines and pharmaceuticals, as well as among different vaccine types, warrant further investigation into reporting practices, actual safety profiles, and potential biases in surveillance systems.