Sample Size Calculation for Clinical Studies on the Efficacy of a New Contraceptive Method

The current guideline of the European Agency for the Evaluation of Medicinal Products (EMEA) on the clinical investigation of steroid contraceptives in women, which was prepared by the Committee for Proprietary Medicinal Products (CPMP), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the reliability of a contraceptive method. The key studies should be large enough to give a Pearl Index with a 95% confidence interval such that the difference between the upper limit of the confidence interval and the corresponding point estimate does not exceed a given margin. As a consequence of this guidance, the success probability of a Pearl Index study is given by its capability, i.e. probability to fulfil this criterion. The resulting power function based on the necessary exposure time does not increase strictly. The minimum exposure time Tmin should be calculated such that this function exceeds a given probability for all T ≥ Tmin. In this paper, the underlying model is discussed, and definitions and formulae are given for the assumption of a Poisson model. The necessary total exposure time is calculated as a function of a given true pregnancy rate. In addition, some simulations were conducted for the model where a drop-out mechanism is incorporated into the process. Assuming an exponential distribution for the time to drop-out the phenomenon that the power does not increase strictly with exposure time is less pronounced. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)