Analysis of studies to evaluate immune response to combination vaccines

The development and evaluation of new combination vaccines is an important public health endeavor. Trials to evaluate these vaccines are customarily d esigned and analyzed as noninferiority studies. We explain the concept of n oninferiority and highlight important issues that can be challenging in the statistical evaluation of these vaccines. Topics covered include end point s, hypotheses, and analyses for comparing geometric mean concentrations (or titers) of antibody and proportion of vaccine recipients responding; covar iate adjustment; the problem of multiplicity and its impact on sample size; and choice of a meaningful difference to rule out.