The Relevance of Goodness‐of‐fit, Robustness and Prediction Validation Categories of OECD‐QSAR Principles with Respect to Sample Size and Model Type

We investigated the relevance of the validation principles on the Quantitative Structure Activity Relationship models issued by Organization for Economic and Co‐operation and Development. We checked the goodness‐of‐fit, robustness and predictivity categories in linear and nonlinear models using benchmark datasets. Most of our conclusions are drawn using the sample size dependence of the different validation parameters. We found that the goodness‐of‐fit parameters misleadingly overestimate the models on small samples. In the case of neural network and support vector models, the feasibility of the goodness‐of‐fit parameters often might be questioned. We propose to use the simplest y‐scrambling method to estimate chance correlation. We found that the leave‐one‐out and leave‐many‐out cross‐validation parameters can be rescaled to each other in all models and the computationally feasible method should be chosen depending on the model type. We assessed the interdependence of the validation parameters by calculating their rank correlations. Goodness of fit and robustness correlate quite well over a sample size for linear models and one of the approaches might be redundant. In the rank correlation between internal and external validation parameters, we found that the assignment of good and bad modellable data to the training or the test causes negative correlations.