Probabilistic uncertainty analysis of epidemiological modeling to guide public health intervention policy

• Dynamic disease modeling of public health interventions rarely accounts for known uncertainties probabilistically.
• Uncertainty distributions for model parameters can be derived by analysis of data.
• Probabilistic parameterization of analytical solutions yields outcome uncertainty.
• Best point estimate predictions would achieve disease mitigation ∼50% of the time.
• Our uncertainty analysis of influenza conveys outcome risk for antiviral and vaccination policy.

Mathematical modeling of disease transmission has provided quantitative predictions for health policy, facilitating the evaluation of epidemiological outcomes and the cost-effectiveness of interventions. However, typical sensitivity analyses of deterministic dynamic infectious disease models focus on model architecture and the relative importance of parameters but neglect parameter uncertainty when reporting model predictions. Consequently, model results that identify point estimates of intervention levels necessary to terminate transmission yield limited insight into the probability of success. We apply probabilistic uncertainty analysis to a dynamic model of influenza transmission and assess global uncertainty in outcome. We illustrate that when parameter uncertainty is not incorporated into outcome estimates, levels of vaccination and treatment predicted to prevent an influenza epidemic will only have an approximately 50% chance of terminating transmission and that sensitivity analysis alone is not sufficient to obtain this information. We demonstrate that accounting for parameter uncertainty yields probabilities of epidemiological outcomes based on the degree to which data support the range of model predictions. Unlike typical sensitivity analyses of dynamic models that only address variation in parameters, the probabilistic uncertainty analysis described here enables modelers to convey the robustness of their predictions to policy makers, extending the power of epidemiological modeling to improve public health.