SAMPLE-SIZE CALCULATION FOR CLINICAL-TRIALS IN WHICH ENTRY CRITERIA AND OUTCOMES ARE COUNTS OF EVENTS

In many chronic diseases, therapy aims to prevent or reduce the freque ncy of episodes of a disease manifestation, for example cardiac ischae mic episodes or epileptic seizures. Entry criteria for clinical trials typically include a minimum number of episodes within a baseline peri od, and regression to the mean should be anticipated. The distribution of the number of episodes at follow-up, the statistical power for tre atment comparisons, and the difficulty of recruitment will depend on t he entry criterion chosen. A gamma-Poisson mixture model is employed t o describe the regression to the mean when the entry criterion and out come measure are counts of discrete events. Sample size formulae which take account of the entry criterion are derived for comparison of mea n number of events at follow-up and the proportion of patients with ze ro events at follow-up. Application of these formulae to screening dat a from the Aymptomatic Cardiac Ischemia Pilot (ACIP) Study is presente d as an example.