Early Phase Programs And Development To An Inflection Point

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.