Pharmaceutical development is a risky, complex, costly, and time-consuming endeavor More than half of development duration is spent in clinical trials. Despite the large number of potential candidates available and the lengthy process of clinical development, the success rate is disappointing. Hence, there is an urgent need for new strategies and methodology for efficient and cost-effective designs to screen potential candidates based on the idea of the proof of the concept for efficacy in a rapid and reliable manner to minimize the total sample size and hence to shorten the duration of the trials. In this article, a two-stage screening design based on continuous efficacy endpoints is proposed. The proposed two-stage screening designs minimize the expected sample size if the new candidate has low efficacy activity subject to the constraint upon the type I and type II error rates. In addition, two-stage screening designs that minimize the maximum sample size (minimax) are presented. Tables of two-stage and minimax designs for various combinations of design parameters are also provided. Applications to the phase 1 and 2 stages of clinical development are illustrated.
