Skip to main content
Top
Published in: BMC Medical Research Methodology 1/2024

Open Access 01-12-2024 | Software

Stacked probability plots of the extended illness-death model using constant transition hazards – an easy to use shiny app

Authors: Marlon Grodd, Susanne Weber, Martin Wolkewitz

Published in: BMC Medical Research Methodology | Issue 1/2024

Login to get access

Abstract

Background

Extended illness-death models (a specific class of multistate models) are a useful tool to analyse situations like hospital-acquired infections, ventilation-associated pneumonia, and transfers between hospitals. The main components of these models are hazard rates and transition probabilities. Calculation of different measures and their interpretation can be challenging due to their complexity.

Methods

By assuming time-constant hazards, the complexity of these models becomes manageable and closed mathematical forms for transition probabilities can be derived. Using these forms, we created a tool in R to visualize transition probabilities via stacked probability plots.

Results

In this article, we present this tool and give some insights into its theoretical background. Using published examples, we give guidelines on how this tool can be used. Our goal is to provide an instrument that helps obtain a deeper understanding of a complex multistate setting.

Conclusion

While multistate models (in particular extended illness-death models), can be highly complex, this tool can be used in studies to both understand assumptions, which have been made during planning and as a first step in analysing complex data structures. An online version of this tool can be found at https://​eidm.​imbi.​uni-freiburg.​de/​.
Appendix
Available only for authorised users
Literature
2.
go back to reference Beyer U, Dejardin D, Meller M, Rufibach K, Burger HU. A multistate model for early decision-making in oncology. Biom J Mai. 2020;62(3):550–67.CrossRef Beyer U, Dejardin D, Meller M, Rufibach K, Burger HU. A multistate model for early decision-making in oncology. Biom J Mai. 2020;62(3):550–67.CrossRef
3.
go back to reference Erdmann A, Beyersmann J, Rufibach K. Oncology clinical trial design planning based on a multistate model that jointly models progression-free and overall survival endpoints. 2023 [zitiert 13. Februar 2024]; Verfügbar unter: https://arxiv.org/abs/2301.10059. Erdmann A, Beyersmann J, Rufibach K. Oncology clinical trial design planning based on a multistate model that jointly models progression-free and overall survival endpoints. 2023 [zitiert 13. Februar 2024]; Verfügbar unter: https://​arxiv.​org/​abs/​2301.​10059.
4.
go back to reference Wolkewitz M, Cooper BS, Bonten MJM, Barnett AG, Schumacher M. Interpreting and comparing risks in the presence of competing events. BMJ 21 August. 2014;349(aug21 5):g5060–5060. Wolkewitz M, Cooper BS, Bonten MJM, Barnett AG, Schumacher M. Interpreting and comparing risks in the presence of competing events. BMJ 21 August. 2014;349(aug21 5):g5060–5060.
5.
go back to reference Schumacher M, Allignol A, Beyersmann J, Binder N, Wolkewitz M. Hospital-acquired infections–appropriate statistical treatment is urgently needed! Int J Epidemiol 1 Oktober. 2013;42(5):1502–8.CrossRef Schumacher M, Allignol A, Beyersmann J, Binder N, Wolkewitz M. Hospital-acquired infections–appropriate statistical treatment is urgently needed! Int J Epidemiol 1 Oktober. 2013;42(5):1502–8.CrossRef
6.
go back to reference von Cube M, Schumacher M, Wolkewitz M. Basic parametric analysis for a multi-state model in hospital epidemiology. BMC Med Res Methodol Dezember. 2017;17(1):111.CrossRef von Cube M, Schumacher M, Wolkewitz M. Basic parametric analysis for a multi-state model in hospital epidemiology. BMC Med Res Methodol Dezember. 2017;17(1):111.CrossRef
7.
go back to reference Pierce RA, Lessler J, Milstone AM. Expanding the statistical toolbox: analytic approaches for cohort studies with healthcare-associated infectious outcomes. Curr Opin Infect Dis August. 2015;28(4):384–91.CrossRef Pierce RA, Lessler J, Milstone AM. Expanding the statistical toolbox: analytic approaches for cohort studies with healthcare-associated infectious outcomes. Curr Opin Infect Dis August. 2015;28(4):384–91.CrossRef
8.
go back to reference Schumacher M, Wangler M, Wolkewitz M, Beyersmann J. Attributable mortality due to nosocomial infections: a simple and useful application of Multistate models. Methods Inf Med. 2007;46(05):595–600.CrossRefPubMed Schumacher M, Wangler M, Wolkewitz M, Beyersmann J. Attributable mortality due to nosocomial infections: a simple and useful application of Multistate models. Methods Inf Med. 2007;46(05):595–600.CrossRefPubMed
9.
go back to reference Wolkewitz M, von Cube M, Schumacher M. Multistate modeling to analyze nosocomial infection data: an introduction and demonstration. Infect Control Hosp Epidemiol August. 2017;38(08):953–9.CrossRef Wolkewitz M, von Cube M, Schumacher M. Multistate modeling to analyze nosocomial infection data: an introduction and demonstration. Infect Control Hosp Epidemiol August. 2017;38(08):953–9.CrossRef
10.
go back to reference Jackson CH, Tom BD, Kirwan PD, Mandal S, Seaman SR, Kunzmann K. u. a. A comparison of two frameworks for multi-state modelling, applied to outcomes after hospital admissions with COVID-19. Stat Methods Med Res September. 2022;31(9):1656–74.CrossRef Jackson CH, Tom BD, Kirwan PD, Mandal S, Seaman SR, Kunzmann K. u. a. A comparison of two frameworks for multi-state modelling, applied to outcomes after hospital admissions with COVID-19. Stat Methods Med Res September. 2022;31(9):1656–74.CrossRef
11.
go back to reference François B, Chastre J, Eggiman P, Laterre PF, Torres A, Sanchez M. u. a. The SAATELLITE and EVADE clinical studies within the COMBACTE Consortium: a public–private collaborative effort in Designing and performing clinical trials for Novel Antibacterial drugs to prevent nosocomial pneumonia: table 1. Clin Infect Dis 15 August. 2016;63(suppl 2):S46–51.CrossRef François B, Chastre J, Eggiman P, Laterre PF, Torres A, Sanchez M. u. a. The SAATELLITE and EVADE clinical studies within the COMBACTE Consortium: a public–private collaborative effort in Designing and performing clinical trials for Novel Antibacterial drugs to prevent nosocomial pneumonia: table 1. Clin Infect Dis 15 August. 2016;63(suppl 2):S46–51.CrossRef
12.
go back to reference Chastre J, François B, Bourgeois M, Komnos A, Ferrer R, Rahav G. u. a. Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. Crit Care 15 November. 2022;26(1):355.CrossRef Chastre J, François B, Bourgeois M, Komnos A, Ferrer R, Rahav G. u. a. Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. Crit Care 15 November. 2022;26(1):355.CrossRef
13.
go back to reference von Cube M, Grodd M, Wolkewitz M, Hazard D, Wengenmayer T, Canet E. u. a. Harmonizing heterogeneous endpoints in Coronavirus Disease 2019 trials without loss of information. Crit Care Med Januar. 2021;49(1):e11–9.CrossRef von Cube M, Grodd M, Wolkewitz M, Hazard D, Wengenmayer T, Canet E. u. a. Harmonizing heterogeneous endpoints in Coronavirus Disease 2019 trials without loss of information. Crit Care Med Januar. 2021;49(1):e11–9.CrossRef
15.
go back to reference Hazard D, Kaier K, von Cube M, Grodd M, Bugiera L, Lambert J. u. a. Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: a multistate approach. BMC Med Res Methodol Dezember. 2020;20(1):206.CrossRef Hazard D, Kaier K, von Cube M, Grodd M, Bugiera L, Lambert J. u. a. Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: a multistate approach. BMC Med Res Methodol Dezember. 2020;20(1):206.CrossRef
16.
go back to reference Wolkewitz M, Vonberg R, Grundmann H, Beyersmann J, Gastmeier P, Bärwolff S. u. a. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2):R44.CrossRefPubMedPubMedCentral Wolkewitz M, Vonberg R, Grundmann H, Beyersmann J, Gastmeier P, Bärwolff S. u. a. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2):R44.CrossRefPubMedPubMedCentral
17.
go back to reference Sitbon O, Channick R, Chin KM, Frey A, Gaine S. Galiè N, u. a. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med 24 Dezember. 2015;373(26):2522–33.CrossRef Sitbon O, Channick R, Chin KM, Frey A, Gaine S. Galiè N, u. a. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med 24 Dezember. 2015;373(26):2522–33.CrossRef
19.
go back to reference Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med 20 Mai. 2007;26(11):2389–430.CrossRef Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med 20 Mai. 2007;26(11):2389–430.CrossRef
20.
go back to reference Cook RJ, Lawless JF. Multistate models for the analysis of life history data. Boca Raton, FL: CRC; 2018.CrossRef Cook RJ, Lawless JF. Multistate models for the analysis of life history data. Boca Raton, FL: CRC; 2018.CrossRef
21.
go back to reference Bühler A, Cook RJ, Lawless JF. Multistate models as a framework for estimand specification in clinical trials of complex processes. Stat Med 30 April. 2023;42(9):1368–97.CrossRef Bühler A, Cook RJ, Lawless JF. Multistate models as a framework for estimand specification in clinical trials of complex processes. Stat Med 30 April. 2023;42(9):1368–97.CrossRef
23.
go back to reference Hougaard P. Analysis of multivariate survival data. New York: Springer; 2000. p. 542.CrossRef Hougaard P. Analysis of multivariate survival data. New York: Springer; 2000. p. 542.CrossRef
24.
go back to reference Lafuente M, López FJ, Mateo PM, Cebrián AC, Asín J, Moler JA. u. a. A multistate model and its standalone tool to predict hospital and ICU occupancy by patients with COVID-19. Heliyon Februar. 2023;9(2):e13545.CrossRef Lafuente M, López FJ, Mateo PM, Cebrián AC, Asín J, Moler JA. u. a. A multistate model and its standalone tool to predict hospital and ICU occupancy by patients with COVID-19. Heliyon Februar. 2023;9(2):e13545.CrossRef
Metadata
Title
Stacked probability plots of the extended illness-death model using constant transition hazards – an easy to use shiny app
Authors
Marlon Grodd
Susanne Weber
Martin Wolkewitz
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2024
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/s12874-024-02240-3

Other articles of this Issue 1/2024

BMC Medical Research Methodology 1/2024 Go to the issue