The Importance of Being Earnest: Validation is the Absolute Essential for Successful Application and Interpretation of QSPR Models

Abstract This paper emphasizes the importance of rigorous validation as a crucial, integral component of Quantitative Structure Property Relationship (QSPR) model development. We consider some examples of published QSPR models, which in spite of their high fitted accuracy for the training sets and apparent mechanistic appeal, fail rigorous validation tests, and, thus, may lack practical utility as reliable screening tools. We present a set of simple guidelines for developing validated and predictive QSPR models. To this end, we discuss several validation strategies including (1) randomization of the modelled property, also called Y‐scrambling, (2) multiple leave‐many‐out cross‐validations, and (3) external…