ABSTRACT

One of the major challenges when conducting a clinical trial for investigation of treatments or drugs for rare disease is probably endpoint selection and power analysis for sample size based on the selected study endpoint. In clinical trials, a prestudy power analysis for sample size calculation is often performed to ensure that an intended clinical trial will achieve the desired power in order to correctly detect a clinically meaningful treatment effect at a prespecified level of significance. For clinical trials with extremely low incidence rates, the sample size required for achieving a desired power to detect a small difference may not be feasible. Sample size justification based on a small difference may not be of practical interest. For vaccine clinical trials with an extremely low incidence rate, it will take a large sample to observe a few responses. For vaccine clinical trials with extremely low incidence rates, the sample size required is often huge.