By William L. Slone, Ph.D., Demauri Mackie, Ph.D. and Michael F. Murphy, M.D., Ph.D.
For investigational products that may be efficacious in indications sharing a common molecular target or pathophysiological pathway, one possible stratagem for efficient clinical development across multiple indications exploits the use of a master protocol. The impetus for efficiency in early phase clinical research is particularly acute when nonclinical models provide a rationale suggesting applications in multiple clinical targets and when decisions enabling strategic investments require preliminary evidence of safety, tolerance, target engagement, and clinical utility.
In these situations, a clinical research stratagem employing use of a master protocol facilitates program development to an informed inflection point, i.e., a point in clinical development in which sufficient information is available to enable a strategic decision in program evolution. In this early phase scenario, master protocols, created with hypothesis generation intentions serve as a method to evaluate product utility across a portfolio of indications in an organized and efficient manner. Herein, this article provides an overview of master protocols with a focus on variations within basket designs, which may be useful for exploratory and hypothesis generating purposes.