Importance of Examining Incidentality in Vaccine Safety Assessment

The author believes that the principles of statistical methods for vaccine safety can be divided into three categories: comparison of adverse event incidence rates between vaccinated and unvaccinated groups, analysis of incidentality in the vaccinated group, and a combination of both. The first category includes the cohort study; the second, the self-controlled risk interval design (SCRI); and the third, the self-controlled case series method. A single p-value alone should not determine a scientific conclusion, and analysis should be performed using multiple statistical methods with different principles. The author believes that using both the cohort study and the SCRI for analysis is the best method to assess vaccine safety. When the cohort study may not detect a significant difference owing to a low incidence rate of an adverse event in the vaccinated group or a high one in the unvaccinated group, the SCRI may detect it. Because vaccines must have a higher level of safety than the pharmaceuticals used for treatment, vaccine safety is advisable to be assessed using methods that can detect a significant difference even for any value of the incidence rate of an adverse event. The author believes that the analyses of COVID-19 vaccine safety have areas for improvement because the proportion of papers that used the cohort study and the SCRI was negligible.