Comparison of two smoothing methods for exploring waning vaccine effects

We consider the statistical evaluation and estimation of vaccine efficacy w hen the protective effect wanes with time. We reanalyse data from a 5-year trial of two oral cholera vaccines in Matlab, Bangladesh. In this field tri al, one vaccine appears to confer better initial protection than the other, but neither appears to offer protection for a period longer than about 3 y ears. Time-dependent vaccine effects are estimated by obtaining smooth esti mates of a time-varying relative risk RR(t) using survival analysis. We com pare two approaches based on the Cox model in terms of their strategies for detecting time-varying vaccine effects, and their estimation techniques fo r obtaining a time-dependent RR(t) estimate. These methods allow an explora tion of time-varying vaccine effects while making minimal parametric assump tions about the functional form of RR(t) for vaccinated compared with unvac cinated subjects.