Informing Structural Assumptions for Three State Oncology Cost-Effectiveness Models through Model Efficiency and Fit

Abstract

The characteristics and relative strengths and weaknesses of partitioned survival models (PSMs) and state transition models (STMs) for three state oncology cost-effectiveness models have previously been studied. Despite clear and longstanding economic modeling guidelines, more than one structure is rarely presented, and the choice of structure appears correlated more with audience or precedent than disease, decision problem, or available data. One reason may be a lack of guidance and tools available to readily compare measures of internal validity such as the model fit and efficiency of different structures, or sensitivity of results to those choices. To address this gap, methods are presented to evaluate the fit and efficiency of three structures, with an accompanying R software package, psm3mkv. The methods are illustrated by analyzing interim and final analysis datasets of the KEYNOTE-826 randomized controlled trial. At both interim and final analyses, the STM Clock Reset structure provided the best and most efficient fit. Structural uncertainties had been reduced from interim to final analysis. Beyond measures of internal validity, guidelines highlight the importance of reflecting all available data, avoiding model selection purely on the basis of goodness of fit and strongly considering external validity. The method and software allow modelers to more easily evaluate and report model fit and efficiency, examine implicit assumptions, and reveal sensitivities to structural choices.