Introduction: Numerous analyses demonstrate substantial health-economic impacts of primary vaccine effects (preventing or mitigating clinical manifestations of the diseases they target), but vaccines may also be associated with secondary effects, previously known as nonspecific, heterologous, or off-target effects.
Areas covered: We define key concepts to distinguish primary and secondary vaccine effects for health economic analyses, summarized terminology used in different fields, and perform a systematic review of health economic analyses focused on secondary vaccine effects (SVEs).
Expert opinion: Health economists integrate evidence from multiple fields, which often use incomplete or inconsistent definitions. Like regulators and policy makers, health economists require high-quality evidence of specific effects. Consistent with the limited evidence on mechanisms of action for SVEs, the associated health economic literature remains highly limited, with 4 studies identified by our systematic review. The lack of specific and well-controlled evidence that supports quantification of specific SVEs limits the consideration of these effects in vaccine research, development, regulatory, and recommendation decisions and health economic analyses.
Keywords: Adverse effects following immunization; benefit; clinical immunology; cost effectiveness; health economic analysis; nonspecific effects; pharmacovigilance; secondary effects; secondary vaccine effects; vaccines.