Let be the transition intensity from state to , and let be the transition intensity matrix, with . For a continuous-time multi-state model with the time-homogeneous Markov property, the transition probability matrix is , with entry . Condition on each recorded initial state. Panel visits contribute transition probabilities; an exact entry into the absorbing death state contributes a statistical probability density
This mixed panel and exact-death likelihood sums over the living state just before death. It accounts for survival until the event; replacing its final factor by would count deaths throughout the interval.
Using the actual visit times recovered from the PDF, the three individual likelihood contributions are
Here means with , not a transition probability. Subjects 8 and 9 supply no event-density factor after their last panel observation. Assume independent subjects and noninformative examination and censoring times; conditional on their observation schedule, its distribution supplies no additional statistical parameter-dependent factor. The patients' covariates can be incorporated by using their own in these same expressions.
For the progressive structure used in the subsequent output, put , , and . The progressive illness-death model permits no recovery, so
When , the continuous limit is . Thus the likelihood contributions simplify to
Intermediate unobserved disease transitions remain integrated into each panel transition probability.
The fitted progressive illness-death model has three allowed arrows: with estimated transition intensity , with , and with , all in years. State 3 is an absorbing state, and state 2 has no return arrow.
Figure 1.
Progressive three-state model with estimated annual transition intensities
.
Once in state 2, the holding time has an exponential distribution with rate , so the mean holding time from a transition intensity matrix is
Apply a confidence interval for an inverse rate to the printed rate interval : since inversion reverses order, the approximate 95% interval for the mean is
The time-homogeneous Markov property makes the future depend only on the current state; the exponential distribution also has the memoryless property. For a person currently in state 2,
Equivalently, . Thus the fitted two-year death probability is approximately 11.6%.