Model selection for clustering of pharmacokinetic responses

Background and Objective: Pharmacokinetics comprises the study of drug absorption, distribution, metabolism and excretion over time. Clinical pharmacokinetics, focusing on therapeutic management, offers important insights towards personalised medicine through the study of efficacy and toxicity of drug therapies. This study is hampered by subject's high variability in drug blood concentration, when starting a therapy with the same drug dosage. Clustering of pharmacokinetics responses has been addressed recently as a way to stratify subjects and provide different drug doses for each stratum. This clustering method, however, is not able to automatically determine the correct number of clusters, using an user-defined parameter for collapsing clusters that are closer than a given heuristic threshold. We aim to use information-theoretical approaches to address parameter-free model selection. Methods: We propose two model selection criteria for clustering pharmacokinetics responses, founded on the Minimum Description Length and on the Normalised Maximum Likelihood. Results: Experimental results show the ability of model selection schemes to unveil the correct number of clusters underlying the mixture of pharmacokinetics responses. Conclusions: In this work we were able to devise two model selection criteria to determine the number of clusters in a mixture of pharmacokinetics curves, advancing over previous works. A cost-efficient parallel implementation in Java of the proposed method is publicly available for the community. (C) 2018 Elsevier B.V. All rights reserved.