Keywords: Phase 2/3, type I error rate, adaptive seamless design
An adaptive seamless Phase 2/3 design in drugs and biologics is a two-stage design consisting of a learning stage and a confirmatory stage where data from both stages are combined for a final analysis. Such a study design eliminates the “white space” between separate Phase 2 and Phase 3 trials conventionally performed. Trials of this type have been appealing to industry and researchers as they are thought to shorten time in product development and to bring treatments quicker to patients. Adaptive seamless Phase 2/3 design trials that are intended to provide substantial evidence for product approval are reviewed rigorously in regulatory submissions. Like other adaptive design clinical trials, the central issues of concern for seamless design clinical trials such as type I error control, operational logistics, and trial conduct remain the same and need to be addressed during design stage when one is planned. So the integrity of study results is maintained and the overall trial results are interpretable. Though it is appealing, one should recognize that trials of this type do not apply to all product development programs. For example, inadequate dose response information in Phase 2 part could result in selecting dose(s) with safety issues identified later in Phase 3 part and risk of adversely affecting product development. In this presentation, I will provide regulatory experiences and perspectives emphasizing on adaptive seamless Phase 2/3 design clinical trials that are intended to provide the primary evidence for product approval followed by examples and recommendation.