pyDarwin machine learning algorithms application and comparison in nonlinear mixed-effect model selection and optimization.

Forward addition/backward elimination (FABE) has been the standard for population pharmacokinetic model selection (PPK) since NONMEM® was introduced. We investigated five machine learning (ML) algorithms (Genetic algorithm [GA], Gaussian process [GP], random forest [RF], gradient boosted random tree [GBRT], and particle swarm optimization [PSO]) as alternatives to FABE. These algorithms were applied to PPK model selection with a focus on comparing the efficiency and robustness of each of them.

RPEM: Randomized Monte Carlo parametric expectation maximization algorithm.

Inspired from quantum Monte Carlo, by sampling discrete and continuous variables at the same time using the Metropolis-Hastings algorithm, we present a novel, fast, and accurate high performance Monte Carlo Parametric Expectation Maximization (MCPEM) algorithm. We named it Randomized Parametric Expectation Maximization (RPEM). We compared RPEM with NONMEM's Importance Sampling Method (IMP), Monolix's Stochastic Approximation Expectation Maximization (SAEM), and Certara's Quasi-Random Parametric Expectation Maximization (QRPEM) for a realistic two-compartment voriconazole model with ordinary differential equations using simulated data.

pyDarwin: A Machine Learning Enhanced Automated Nonlinear Mixed-Effect Model Selection Toolbox.

pyDarwin is an open-source Python package for nonlinear mixed-effect model selection. pyDarwin combines machine-learning algorithms and NONMEM to perform a global search for the optimal model in a user-defined model search space. Compared with traditional stepwise search, pyDarwin provides an efficient platform for conducting an objective, robust, less labor-intensive model selection process without compromising model interpretability.

Respiratory syncytial virus-A dynamics and the effects of lumicitabine, a nucleoside viral replication inhibitor, in experimentally infected humans.

Background: Respiratory syncytial virus (RSV) causes high morbidity, with mortality rates approaching or exceeding that of influenza in adult and infant patient populations, respectively. Lumicitabine (ALS-008176 or JNJ-64041575) is an oral nucleoside analogue prodrug in clinical development to treat RSV infections. This prodrug converts to plasma-circulating ALS-8112, and then to the 5'-active nucleoside triphosphate (NTP) form within host cells.

A Regression Approach to Visual Predictive Checks for Population Pharmacometric Models.

A visual predictive check (VPC) is a common diagnostic procedure for population pharmacometric models. Typically, VPCs are generated by specifying intervals, or "bins", of an independent variable (e.g.