Exact power and sample size for vaccine efficacy studies

In vaccine efficacy studies the goal is to show that the vaccine reduces the incidence of the disease compared to placebo. In this report we describe two procedures for calculating sample size and power based on exact distributions. In small studies where the disease incidence and the anticipated vaccine efficacy are both high, an unconditional exact procedure is desirable because it guarantees the level of the test and loses little sensitivity. In large studies where the disease incidence is rare, a Poisson approximation to the number of events is reasonable and an exact test is simple to construct conditional on the total number of events. We compare the power and type I error rate of these two exact methods to the method based on the normal approximation for varying disease incidence and sample size.