Background: The use of correlates of protection (CoPs) in vaccination trials offers significant advantages as useful clinical endpoint substitutes. Vaccines with very high vaccine efficacy (VE) are documented in the literature (95% or above). Callegaro and Tibaldi, (2019) showed that the rare infections observed in the
vaccinated groups of these trials poses challenges when applying conventionally-used statistical methods for CoP assessment such as the Prentice criteria and meta-analysis.
Methods: In this paper, we extended Callegaro and Tibaldi, (2019) simulation study by evaluating the impact of high VE on the Principal stratification approach.
Results: Similarly to the Prentice framework, we showed that the power decreases when the VE grows. It follows that it can be challenging to validate a principal surrogate (and a statistical surrogate) when rare infections are observed in the vaccinated groups.