Intent-to-treat analysis and preventive vaccine efficacy

While the intent-to-treat (ITT) concept has often been discussed and debate d in the literature with respect to randomized, placebo-controlled therapeu tic trials, there has been little discussion of this issue in the context o f preventive vaccine efficacy trials. ITT analysis has traditionally played a minor role (if any) in the latter trials. This paper discusses the ITT a pproach to analysis in randomized superiority trials of preventive vaccine efficacy, using clinical endpoints. Data are presented from published liter ature as well as from a simple mathematical model. The data suggest that wh en compliance and efficacy are high, both ITT and "per-protocol" approaches generally lead to similar conclusions regarding the acceptability of a vac cine 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, an d often both will be informative in evaluating preventive vaccines. Publish ed by Elsevier Science Ltd.