Assessment and Reproducibility of Quantitative Structure–Activity Relationship Models by the Nonexpert

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.