Sample size in clinical trials with dichotomous endpoints: use of covariables.

In many clinical trials, the primary endpoint is dichotomous. In this article, we examine the possibility of reducing the required sample size by removing variation associated with baseline covariables. Three measures are used to study the size of the reduction. Simulation studies based on a database of head trauma and of stroke patients suggested that a substantial reduction in the sample size can be achieved when the correlation between the endpoint and covariables is strong. A simple ad hoc formula for approximating the required sample size is proposed.