Intent-to-treat analysis and preventive vaccine efficacy

Area of Science:

• Epidemiology
• Biostatistics
• Vaccinology

Background:

• The intent-to-treat (ITT) principle is widely used in therapeutic randomized controlled trials.
• Its application and implications in preventive vaccine efficacy trials remain less explored.
• Traditional analyses of vaccine trials have often minimized the role of ITT.

Purpose of the Study:

• To discuss the application of the intent-to-treat (ITT) approach in randomized superiority trials for preventive vaccine efficacy.
• To compare ITT analysis with per-protocol analysis in the context of vaccine efficacy evaluation.
• To examine the impact of compliance on the divergence between ITT and per-protocol estimates.

Main Methods:

• Review of published literature on vaccine efficacy trials.
• Development and application of a simple mathematical model to simulate trial outcomes.
• Analysis of clinical endpoints in randomized preventive vaccine efficacy studies.

Main Results:

• When vaccine compliance and efficacy are high, ITT and per-protocol analyses yield similar conclusions on vaccine acceptability.
• Low compliance significantly increases the disparity between ITT and per-protocol estimates of vaccine efficacy.
• Both analytical approaches address distinct and valuable scientific questions.

Conclusions:

• ITT and per-protocol analyses offer complementary insights for evaluating preventive vaccines.
• The choice of analysis method is crucial, particularly when vaccine compliance is suboptimal.
• Understanding the nuances of ITT is essential for accurate vaccine efficacy assessment.