Fig. 1. Relation between incidence of a problem (toxicity) and number of subjects required to study in order to have an 80% probability of observing at least one case of the problem. Neurotoxicity from intrathecal lidocaine in clinical use may be as rare as 1:100,000, meaning more than 300,000 subjects must be studied to have an 80% probability of observing a case. By increasing dose, concentration, or time of exposure, researchers increase the incidence to 1:2, making it feasible to study the phenomenon.