Progression Concept End point Hierarchical prominence Longer Life Overall survival Primary i.e., sufficient Better Life – absence of disease progression Progression-free survival as determined by radiographic and clinical assessment Better Life – clinician-reported function Clinician-rated performance status score Secondary If above two end points are not in the wrong direction, these end points are acceptable as a component of a time-to-event progression metric with swallowing, speaking, and activities Better Life – patient-reported function Swallowing diary score Better Life – patient-reported symptoms Conversation diary score Better Life – patient-reported function Daily activities measure

Table 2: Hypothetical hierarchical end point model for head and neck cancer.