Table 1.

Current and proposed assessment of vaccine safety

	Current phase III trials	Proposed phase III trials
“Placebo”	Some use another vaccine or the adjuvant	Never use another vaccine or the adjuvant if there is no approved vaccine for the targeted infection(s) [because they may also have non-specific effects]
Adverse events	Solicited adverse events collected within a limited time frame. Deaths/hospitalization collected for full duration of the trial. Assessed for plausibility	All clinical symptoms should be actively asked for and recorded and coded for at least 12 months [everything is plausible]
Coding of adverse events	Diagnoses are preferentially coded before signs and symptoms	Symptoms should be given priority
Outcomes	Typically (symptomatic) infection and/or “correlates of protection”	In addition, all infectious diseases and overall mortality and morbidity (e.g., all-cause consultations, hospitalizations, deaths), by sex and age group, as well as biomarkers of non-specific effects, such as in vitro cytokine and immune cell responses to non-related pathogens
Duration of follow-up	Variable. Sometimes the control group is vaccinated once the vaccine is approved	Blinded follow-up of vaccinated and control subjects for at least 12 months

	Current post-licensure surveillance	Proposed post-licensure surveillance
Comparison groups	Observational studies comparing vaccinated vs unvaccinated; before and after comparisons	Randomized trials individually or by cluster; step-wedged roll-out. Powered to study overall health outcomes in both sexes
Safety	Reporting by general practitioners and citizens	Active follow-up through interviews/registers
Outcomes	“Plausible” adverse events	All infectious diseases. Overall mortality and morbidity, e.g., all-cause consultation, hospitalization, deaths