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

Objective: 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 FDA Adverse Event Reporting System (FAERS) and common vaccines in the Vaccine Adverse Events Reporting System (VAERS). For vaccines, we used 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 compared to influenza vaccines. The ratio of total VAERS reports to deaths for vaccines was approximately 70:1 (R²=0.966). For pharmaceuticals, the ratio of total adverse event reports to deaths was about 43:1 (R²=0.697), with a strong correlation between serious adverse events and deaths (ratio 11:1, R²=0.768). Conclusion: 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.