Fig. 1: Prospective risk can be represented as a trajectory.

Red and green zones represent positions on the trajectory corresponding to outward definitions of diseased and non-diseased status. Vertical arrows represent sampling of population at a particular point of a trajectory. A The (single-class) case-control paradigm often imposes a dichotomous (binary) framework onto a continuous trajectory. B Experiments utilizing observations of cases that are concentrated at the time when the case event occurs cannot capture any information regarding the transition trajectory, resulting in temporal bias. C In order to predict a patient’s position along the trajectory, experiments capturing the entire transition from non-diseased to diseased are necessary.