Intent-to-treat analysis and preventive vaccine efficacy.

While the intent-to-treat (ITT) concept has often been discussed and debated in the literature with respect to randomized, placebo-controlled therapeutic trials, there has been little discussion of this issue in the context of preventive vaccine efficacy trials. ITT analysis has traditionally played a minor role (if any) in the latter trials. This paper discusses the ITT approach to analysis in randomized superiority trials of preventive vaccine efficacy, using clinical endpoints. Data are presented from published literature as well as from a simple mathematical model. The data suggest that when compliance and efficacy are high, both ITT and "per-protocol" approaches generally lead to similar conclusions regarding the acceptability of a vaccine for use in a population. However, when compliance is low, the ITT and per-protocol estimates of vaccine efficacy can be widely disparate. ITT and per-protocol analyses address unique and relevant scientific questions, and often both will be informative in evaluating preventive vaccines.