Semiparametric mixed-effect least squares support vector machine for analyzing pharmacokinetic and pharmacodynamic data

In this paper we propose a semiparametric mixed-effect least squares support vector machine (LS-SVM) regression model for the analysis of pharmacokinetic (PK) and pharmacodynamic (PD) data. We also develop the generalized cross-validation (GCV) method for choosing the hyperparameters which affect the performance of the proposed LS-SVM. The performance of the proposed LS-SVM is compared with those of NONMEM and the regular semiparametric LS-SVM via four measures, which are mean squared error (MSE), mean absolute error (MAE), mean relative absolute error (MRAE) and mean relative prediction error (MRPE). Through paired-t test statistic we find that the absolute values of four measures of the proposed LS-SVM are significantly smaller than those of NONMEM for PK and PD data. We also investigate the coefficient of determinations R2's of predicted and observed values. The R2's of NONMEM are 0.66 and 0.59 for PK and PD data, respectively, while the R2's of the proposed LS-SVM are 0.94 and 0.96. Through cross validation technique we also find that the proposed LS-SVM shows better generalization performance than the regular semiparametric LS-SVM for PK and PD data. These facts indicate that the proposed LS-SVM is an appealing tool for analyzing PK and PD data.