Proof of Concept: Drug Selection? Or Dose Selection? Thoughts on Multiplicity Issues

In new drug development process, one of the most important milestones for a drug candidate is to establish Proof of Concept (PoC) at early Phase II stage. Among many challenges in PoC clinical trial design and analysis, the application of multiplicity comparison procedures (MCP) is frequently discussed when multiple doses or drugs are included in one PoC study. In such discussion, one fundamental question of applying multiplicity adjustment is which error one should consider to control and at what level. Should it be the experiment-wise error or the compound-wise error? In this paper, the multiplicity issues in two cases of PoC studies are used as examples to discuss the concept of different types of error and the level of the error rate control. With a clear understanding of the type of error and error rate control, the debate of applications of the multiplicity adjustment procedures in the PoC studies can be reconciled.