Safety Assessment in Pilot Studies When Zero Events Are Observed

Abstract

Pilot studies in clinical research settings frequently focus on estimating the frequency of occurrence of certain adverse events. When zero such events are observed, the question of legitimate inference on the true event rate arises. The relationship between binomial and geometric distributions’ confidence intervals yields two useful graphical displays and interpretations for the event rate inference in this circumstance. The interval is also closely related to the Bayesian credible interval when the prior distribution for the event rate is uniform. In addition, the simple algebraic expression for the confidence bound is seen to be useful in the context of planning studies.