Abstract
Background: We evaluated the implications of different approaches to characterize the uncertainty of calibrated parameters of microsimulation decision models (DMs) and quantified the value of such uncertainty in decision making. Methods: We calibrated the natural history model of CRC to simulated epidemiological data with different degrees of uncertainty and obtained the joint posterior distribution of the parameters using a Bayesian approach. We conducted a probabilistic sensitivity analysis (PSA) on all the model parameters with different characterizations of the uncertainty of the calibrated parameters. We estimated the value of uncertainty of the various characterizations with a value of information analysis. We conducted all analyses using high-performance computing resources running the Extreme-scale Model Exploration with Swift (EMEWS) framework. Results: The posterior distribution had a high correlation among some parameters. The parameters of the Weibull hazard function for the age of onset of adenomas had the highest posterior correlation of -0.958. When comparing full posterior distributions and the maximum-a-posteriori estimate of the calibrated parameters, there is little difference in the spread of the distribution of the CEA outcomes with a similar expected value of perfect information (EVPI) of $653 and $685, respectively, at a willingness-to-pay (WTP) threshold of $66,000 per quality-adjusted life year (QALY). Ignoring correlation on the calibrated parameters' posterior distribution produced the broadest distribution of CEA outcomes and the highest EVPI of $809 at the same WTP threshold. Conclusion: Different characterizations of the uncertainty of calibrated parameters affect the expected value of eliminating parametric uncertainty on the CEA. Ignoring inherent correlation among calibrated parameters on a PSA overestimates the value of uncertainty.