A Multistate Model Incorporating Relative Survival Extrapolation and Mixed Time Scales for Health Technology Assessment

Enoch Yi-Tung Chen (), Paul W. Dickman and Mark S. Clements
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Enoch Yi-Tung Chen: Karolinska Institutet
Paul W. Dickman: Karolinska Institutet
Mark S. Clements: Karolinska Institutet

PharmacoEconomics, 2025, vol. 43, issue 3, No 5, 297-310

Abstract: Abstract Background Multistate models have been widely applied in health technology assessment. However, extrapolating survival in a multistate model setting presents challenges in terms of precision and bias. In this article, we develop an individual-level continuous-time multistate model that integrates relative survival extrapolation and mixed time scales. Methods We illustrate our proposed model using an illness–death model. We model the transition rates using flexible parametric models. We update the hesim package and the microsimulation package in R to simulate event times from models with mixed time scales. This feature allows us to incorporate relative survival extrapolation in a multistate setting. We compare several multistate settings with different parametric models (standard vs. flexible parametric models), and survival frameworks (all-cause vs. relative survival framework) using a previous clinical trial as an illustrative example. Results Our proposed approach allows relative survival extrapolation to be carried out in a multistate model. In the example case study, the results agreed better with the observed data than did the commonly applied approach using standard parametric models within an all-cause survival framework. Conclusions We introduce a multistate model that uses flexible parametric models and integrates relative survival extrapolation with mixed time scales. It provides an alternative to combine short-term trial data with long-term external data within a multistate model context in health technology assessment.

Date: 2025
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DOI: 10.1007/s40273-024-01457-w

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