Abstract
In clinical trials, statistical analyses on incidence rates detect significant differences between the responses from groups. Sample size estimation is always one of the key aspects in clinical trials that have limited budgets. A prestudy power analysis for sample size calculation is often performed to select an appropriate sample size that will achieve a desired power (ie, the probability of correctly detecting the significant difference if such a difference truly exists) at a prespecified level of significance. In practice, it is expected that a greater sample size is needed to detect a smaller difference. A much larger sample size is required to detect a relatively small difference, especially for those clinical studies with extremely low incidence rates. Thus, sample size calculation based on prestudy power analysis may not be feasible in practice. In this case, as an alternative, the authors propose to justify a selected sample size based on a precision analysis and a sensitivity analysis. A recommended step-by-step procedure for sample size determination in clinical trials with extremely low incidence rate is given. A statistical procedure for data safety monitoring based on the probability statement during the conduct of the clinical trial is also proposed.