Comparison of Timed Automata with Discrete Event Simulation for Modeling of Biomarker-Based Treatment Decisions: An Illustration for Metastatic Castration-Resistant Prostate Cancer

Koen Degeling, Stefano Schivo, Niven Mehra, Hendrik Koffijberg, Romanus Langerak, Johann de Bono, Maarten Joost IJzerman

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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Abstract

Background: With the advent of personalized medicine, the field of health economic modeling is being challenged and the use of patient-level dynamic modeling techniques might be required.

Objectives: To illustrate the usability of two such techniques, timed automata (TA) and discrete event simulation (DES), for modeling personalized treatment decisions.

Methods: An early health technology assessment on the use of circulating tumor cells, compared with prostate-specific antigen and bone scintigraphy, to inform treatment decisions in metastatic castration-resistant prostate cancer was performed. Both modeling techniques were assessed quantitatively, in terms of intermediate outcomes (e.g., overtreatment) and health economic outcomes (e.g., net monetary benefit). Qualitatively, among others, model structure, agent interactions, data management (i.e., importing and exporting data), and model transparency were assessed.

Results: Both models yielded realistic and similar intermediate and health economic outcomes. Overtreatment was reduced by 6.99 and 7.02 weeks by applying circulating tumor cell as a response marker at a net monetary benefit of −€1033 and −€1104 for the TA model and the DES model, respectively. Software-specific differences were observed regarding data management features and the support for statistical distributions, which were considered better for the DES software. Regarding method-specific differences, interactions were modeled more straightforward using TA, benefiting from its compositional model structure.

Conclusions: Both techniques prove suitable for modeling personalized treatment decisions, although DES would be preferred given the current software-specific limitations of TA. When these limitations are resolved, TA would be an interesting modeling alternative if interactions are key or its compositional structure is useful to manage multi-agent complex problems.
Original languageEnglish
Pages (from-to)1411-1419
JournalValue in health
Volume20
Issue number10
DOIs
Publication statusPublished - Dec 2017

Keywords

  • Advanced modeling methods
  • Discrete event simulation
  • Health economic modeling
  • Personalized treatment decisions
  • Timed automata

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