A framework for joint modeling and joint assessment of efficacy and safety endpoints for probability of success...

The evaluation of clinical proof of concept, optimal dose selection, and phase III probability of success has traditionally been conducted by a subjective and qualitative assessment of the efficacy and safety data. This, in part, was responsible for the numerous failed phase III programs in the past. The need to utilize more quantitative approaches to assess efficacy and safety profiles has never been greater. In this paper, we propose a framework that incorporates efficacy and safety data simultaneously for the joint evaluation of clinical proof of concept, optimal dose selection, and phase III probability of success. Simulation studies were conducted to evaluate the properties of our proposed methods. The proposed approach was applied to two real clinical studies. On the basis of the true outcome of the two clinical studies, the assessment based on our proposed approach suggested a reasonable path forward for both clinical programs.