Score tests based on a finite mixture model of Markov processes under intermittent observation

Stat Med. 2019 Jul 20;38(16):3013-3025. doi: 10.1002/sim.8155. Epub 2019 Apr 10.


A mixture model is described, which accommodates different Markov processes governing disease progression in a finite set of latent classes. We give special attention to the setting in which individuals are examined intermittently and transition times are consequently interval censored. A score test is developed to identify genetic markers associated with class membership. Simulation studies are conducted to validate the algorithm, assess the finite sample properties of the estimators, and assess the frequency properties of the score tests. A permutation test is recommended for settings when there is concern that the asymptotic approximation to the score test is poor. An application involving progression in joint damage in psoriatic arthritis (PsA) provides illustration and identifies human leukocyte antigen markers associated with unilateral and bilateral sacroiliac damage in individuals with PsA.

Keywords: Markov process; finite mixture model; intermittent observation; multistate model; score test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Arthritis, Psoriatic / genetics
  • Biomarkers*
  • Computer Simulation
  • Disease Progression
  • Humans
  • Markov Chains*
  • Models, Statistical


  • Biomarkers