Use of sample size for estimating efficacy of a vaccine against an infectious disease.

OBJECTIVE: To determine the sample size necessary to evaluate the efficacy of a vaccine in a population. PROCEDURE: An equation was coded into a computer spreadsheet to compare the traditional sample size calculation with that needed when evaluating the efficacy of a vaccine applied in a population. RESULTS: The traditional approach used to conservatively estimate sample size necessary to detect a given difference in group proportions potentially greatly underestimates the number of animals needed for vaccine efficacy (VE) trials. In VE trials, it is necessary to estimate the effect of population-level vaccination prior to estimating sample size. In VE trials, as incidence proportion in the population or herd decreases or VE decreases, necessary sample size increases. CONCLUSIONS AND CLINICAL RELEVANCE: In designing a clinical or field trial, such as one to evaluate the efficacy of a vaccine against an infectious disease in a population, one needs to approach sample size calculations in a nontraditional manner. The proportion of the population vaccinated, disease transmission dynamics, and VE will affect the incidence in the nonvaccinated and vaccinated groups and, hence, sample size. Thus, estimation of the effect of the vaccination on the population must be made prior to calculating sample size. Otherwise, sample size and the power to identify VE will be insufficient.