Deconstructing HARI on The Dynamical Analysis of Clinical Trial Outcomes

Kaplan-Meier survival analysis [1] and Cox proportional hazards regression [2] are commonly used to assess outcomes in randomized clinical trials. These methods typically employ a simple two-state non-deterministic model to represent the transition from an initial baseline state to a terminal outcome state (often a composite of multiple endpoints). Many pathophysiological processes, however, involve a deterministic sequence of some number of intermediate transitions: from the baseline state to unstable angina (UA) to myocardial infarction (MI), for example. In such cases, the simple two-state model may be insufficient to capture important dynamics of the actual underlying clinical process.