Hazardous to Your Health: Kinetic Foundations of Risk Stratification and Therapeutic Triage

Background Risk stratification is widely used in the prognostic assessment of patients with a variety of clinical disorders on the unquestioned assumption that the intensity of treatment should be proportionate to the threat of an adverse event over some finite period of time (risk). However, just as the physical trajectory of an object depends on its current magnitude of displacement (velocity) and the concurrent rate of change of that displacement (acceleration), the prognostic trajectory of a patient depends on the current magnitude of risk and the concurrent rate of change of that risk (hazard). Clinical risk stratification nevertheless relies only on the former. Methods We therefore integrated the quantitative assessment of risk and hazard by way of a kinetic model that characterizes the development of an adverse event as a series of exponential state-to-state transitions—from stable to unstable to event. This model serves to shift the clinical emphasis from prognosis (the assessment of risk) to treatment (the improvement in outcome). In this context, treatment is well advised (even in low-risk individuals) when the hazard is large (risk is rising), and is less well advised (even in high-risk individuals) when the hazard is small (risk is stable). Results The kinetic model outlined here thereby promises to supersede the superficial practice of risk stratification with a more sophisticated strategy of therapeutic triage that allows one to predict the incremental clinical benefit of alternative treatment strategies.