Therapeutic drug monitoring of kidney transplant recipients using profiled support vector machines

This paper proposes a twofold approach for therapeutic drug monitoring (TDM) of kidney recipients using support vector machines (SVMs), for both predicting and detecting Cyclosporine A (CyA) blood concentrations. The final goal is to build useful, robust, and ultimately understandable models for individualizing the dosage of CyA. We compare SVMs with several neural network models, such as the multilayer perceptron (MLP), the Elman recurrent network, finite/infinite impulse response networks, and neural network ARMAX approaches. In addition, we present a profile-dependent SVM (PD-SVM), which incorporates a priori knowledge in both tasks. Models are compared numerically, statistically, and in the presence of additive noise. Data from 57 renal allograft recipients were used to develop the models. Patients followed a standard triple therapy, and CyA trough concentration was the dependent variable. The best results for the CyA blood concentration prediction were obtained using the PD-SVM (mean error of 0.36 ng/mL and root-mean-square error of 52.01 ng/mL in the validation set) and appeared to be more robust in the presence of additive noise. The proposed PD-SVM improved results from the standard SVM and MLP, specially significant (both numerical and statistically) in the one-against-all scheme. Finally, some clinical conclusions were obtained from sensitivity rankings of the models and distribution of support vectors. We conclude that the PD-SVM approach produces more accurate and robust models than do neural networks. Finally, a software tool for aiding medical decision-making including the prediction models is presented.