Model Averaging in Viral Dynamic Models

The paucity of experimental data makes both inference and prediction particularly challenging in viral dynamic models. In the presence of several candidate models, a common strategy is model selection (MS), in which models are fitted to the data but only results obtained with the "best model" are presented. However, this approach ignores model uncertainty, which may lead to inaccurate predictions. When several models provide a good fit to the data, another approach is model averaging (MA) that weights the predictions of each model according to its consistency to the data. Here, we evaluated by simulations in a nonlinear mixed-effect model framework the performances of MS and MA in two realistic cases of acute viral infection, i.e., (1) inference in the presence of poorly identifiable parameters, namely, initial viral inoculum and eclipse phase duration, (2) uncertainty on the mechanisms of action of the immune response. MS was associated in some scenarios with a large rate of false selection. This led to a coverage rate lower than the nominal coverage rate of 0.95 in the majority of cases and below 0.50 in some scenarios. In contrast, MA provided better estimation of parameter uncertainty, with coverage rates ranging from 0.72 to 0.98 and mostly comprised within the nominal coverage rate. Finally, MA provided similar predictions than those obtained with MS. In conclusion, parameter estimates obtained with MS should be taken with caution, especially when several models well describe the data. In this situation, MA has better performances and could be performed to account for model uncertainty.