Agent-based modeling in medical research, virtual baseline generator and change in patients' profile issue

Simulation studies are promising in medical research in particular to improve drug development. For instance, one can aim to develop In Silico Clinical Trial in order to challenge trial's design parameters in terms of feasibility and probability of success of the trial. Approaches based on agent-based models draw on a particularly useful framework to simulate patients evolution. In this paper, an approach based on agent-based modeling is described and discussed in the context of medical research. An R-vine copula model is used to represent the multivariate distribution of the data. A baseline data cohort can then be simulated and execution models can be developed to simulate the evolution of patients. R-vine copula models are very flexible tools which allow researchers to consider different marginal distributions than the ones observed in the data. It is then possible to perform data augmentation to explore a new population by simulating baseline data which are slightly different than those of the original population. A simulation study illustrates the efficiency of copula modeling to generate data according to specific marginal distributions but also highlights difficulties inherent to data augmentation.