Assessment and Reproducibility of Quantitative Structure–Activity Relationship Models by the Nonexpert
Mukesh Patel, Martyn L. Chilton, Andrea Sartini, Laura Gibson, Chris Barber, Liz Covey-Crump, Katarzyna R. Przybylak, Mark T. D. Cronin, Judith C. Madden
文献索引：10.1021/acs.jcim.7b00523
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摘要
Model reliability is generally assessed and reported as an intrinsic component of quantitative structure–activity relationship (QSAR) publications; it can be evaluated using defined quality criteria such as the Organisation for Economic Cooperation and Development (OECD) principles for the validation of QSARs. However, less emphasis is afforded to the assessment of model reproducibility, particularly by users who may wish to use model outcomes for decision making, but who are not QSAR experts. In this study we identified a range of QSARs in the area of absorption, distribution, metabolism, and elimination (ADME) prediction and assessed their adherence to the OECD principles, as well as investigating their reproducibility by scientists without expertise in QSAR. Here, 85 papers were reviewed, reporting over 80 models for 31 ADME-related endpoints. Of these, 12 models were identified that fulfilled at least 4 of the 5 OECD principles and 3 of these 12 could be readily reproduced. Published QSAR models should aim to meet a standard level of quality and be clearly communicated, ensuring their reproducibility, to progress the uptake of the models in both research and regulatory landscapes. A pragmatic workflow for implementing published QSAR models and recommendations to modellers, for publishing models with greater usability, are presented herein.