Skip to main content
Log in

Inference for transition probabilities in non-Markov multi-state models

  • Published:
Lifetime Data Analysis Aims and scope Submit manuscript

Abstract

Multi-state models are frequently used when data come from subjects observed over time and where focus is on the occurrence of events that the subjects may experience. A convenient modeling assumption is that the multi-state stochastic process is Markovian, in which case a number of methods are available when doing inference for both transition intensities and transition probabilities. The Markov assumption, however, is quite strict and may not fit actual data in a satisfactory way. Therefore, inference methods for non-Markov models are needed. In this paper, we review methods for estimating transition probabilities in such models and suggest ways of doing regression analysis based on pseudo observations. In particular, we will compare methods using land-marking with methods using plug-in. The methods are illustrated using simulations and practical examples from medical research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Aalen OO, Johansen S (1978) An empirical transition matrix for nonhomogeneous Markov chains based on censored observations. Scand J Stat 5:141–150

    MATH  Google Scholar 

  • Allignol A, Beyersmann J, Gerds TA, Latouche A (2014) A competing risks approach for nonparametric estimation of transition probabilities in a non-Markov illness–death model. Lifetime Data Anal 20:495–513

    Article  MathSciNet  Google Scholar 

  • Andersen PK, Borgan Ø, Gill RD, Keiding N (1993) Statistical models based on counting processes. Springer, New York

    Book  Google Scholar 

  • Andersen PK, Keiding N (2002) Multi-state models for event history analysis. Stat Methods Med Res 11:91–115

    Article  Google Scholar 

  • Andersen PK, Klein JP, Rosthøj S (2003) Generalized linear models for correlated pseudo-observations, with applications to multi-state models. Biometrika 90:15–27

    Article  MathSciNet  Google Scholar 

  • Andersen PK, Pohar Perme M (2008) Inference for outcome probabilities in multi-state models. Lifetime Data Anal 14:405–431

    Article  MathSciNet  Google Scholar 

  • Andersen PK, Pohar Perme M (2010) Pseudo-observations in survival analysis. Stat Methods Med Res 19:71–99

    Article  MathSciNet  Google Scholar 

  • Azarang L, Scheike T, Uña-Alvarez J (2017) Direct modeling of regression effects for transition probabilities in the progressive illness–death model. Stat Med 36:1964–1976

    MathSciNet  Google Scholar 

  • Cook RJ, Lawless JF (2018) Multistate models for the analysis of life history data. CRC/Chapman and Hall, Boca Raton

    Book  Google Scholar 

  • Cox DR (1972) Regression models and life-tables (with discussion). J R Stat Soc B 34:187–220

    MATH  Google Scholar 

  • Datta S, Satten GA (2001) Validity of the Aalen–Johansen estimators of stage occupation probabilities and Nelson–Aalen estimators of integrated transition hazards for non-Markov models. Stat Probab Lett 55:403–411

    Article  MathSciNet  Google Scholar 

  • Gill RD, Johansen S (1990) A survey of product-integration with a view towards application in survival analysis. Ann Stat 18:1501–1555

    Article  MathSciNet  Google Scholar 

  • Malzahn N, Hoff R, Aalen OO, Mehlum IS, Putter H, Gran JM (2021) A hybrid landmark Aalen–Johansen estimator for transition probabilities in partially non-Markov multi-state models. Lifetime Data Anal 27:737–760

    Article  MathSciNet  Google Scholar 

  • Meira-Machado L, Uña-Alvarez J, Cadarso-Saurez C (2006) Nonparametric estimation of transition probabilities in a non-Markov illness–death model. Lifetime Data Anal 13:325–344

    Article  MathSciNet  Google Scholar 

  • Meira-Machado L, Sestelo M (2017) Estimation in the progressive illness–death model: a nonexhaustive review. Biom. J. 61:245–263

    Article  MathSciNet  Google Scholar 

  • Mitton L, Sutherland H, Week M (eds) (2000) Microsimulation modelling for policy analysis. Challenges and innovations. Cambridge University Press, Cambridge

    Google Scholar 

  • Overgaard M, Parner ET, Pedersen J (2017) Asymptotic theory of generalized estimating equations based on jack-knife pseudo-observations. Ann Stat 45:1988–2015

    Article  MathSciNet  Google Scholar 

  • Pepe MS (1991) Inference for events with dependent risks in multiple endpoint studies. J Am Stat Assoc 86:770–778

    Article  MathSciNet  Google Scholar 

  • PROVA Study Group (1991) Prophylaxis of first time hemorrage from esophageal varices by sclerotherapy, propranolol or both in cirrhotic patients: a randomized multicenter trial. Hepatology 14:1016–1024

    Article  Google Scholar 

  • Putter H, Spitoni C (2018) Non-parametric estimation of transition probabilities in non-Markov multi-state models: the landmark Aalen–Johansen estimator. Stat Methods Med Res 27:2081–2092

    Article  MathSciNet  Google Scholar 

  • Rodriguez-Girondo M, Uña-Alvarez J (2012) A nonparametric test for Markovianity in the illness–death model. Stat Med 31:4416–4427

    Article  MathSciNet  Google Scholar 

  • Scheike TH, Zhang M-J (2007) Direct modelling of regression effects for transition probabilities in multistate models. Scand J Stat 34:17–32

    Article  MathSciNet  Google Scholar 

  • Shu Y, Klein JP, Zhang M-J (2007) Asymptotic theory for the Cox semi-Markov illness–death model. Lifetime Data Anal 13:91–117

  • Titman AC (2015) Transition probability estimates for non-Markov multi-state models. Biometrics 71:1034–1041

  • Titman AC, Putter H (2022) General tests of the Markov property in multi-state models. Biostatistics 23:380–396

    Article  MathSciNet  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Per Kragh Andersen.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (pdf 172 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andersen, P.K., Wandall, E.N.S. & Pohar Perme, M. Inference for transition probabilities in non-Markov multi-state models. Lifetime Data Anal 28, 585–604 (2022). https://doi.org/10.1007/s10985-022-09560-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10985-022-09560-w

Keywords

Navigation