Ensuring confidence in predictions: A scheme to assess the scientific validity of in silico models

Advanced Drug Delivery Reviews
Mark HewittJudith C Madden

Abstract

The use of in silico tools within the drug development process to predict a wide range of properties including absorption, distribution, metabolism, elimination and toxicity has become increasingly important due to changes in legislation and both ethical and economic drivers to reduce animal testing. Whilst in silico tools have been used for decades there remains reluctance to accept predictions based on these methods particularly in regulatory settings. This apprehension arises in part due to lack of confidence in the reliability, robustness and applicability of the models. To address this issue we propose a scheme for the verification of in silico models that enables end users and modellers to assess the scientific validity of models in accordance with the principles of good computer modelling practice. We report here the implementation of the scheme within the Innovative Medicines Initiative project "eTOX" (electronic toxicity) and its application to the in silico models developed within the frame of this project.

References

May 1, 1977·Journal of Toxicology and Environmental Health·J B Krause
Feb 1, 1997·Regulatory Toxicology and Pharmacology : RTP·H J KlimischU Tillmann
Apr 6, 2005·Journal of Chemical Information and Modeling·Rajendra KristamDavid Thorner
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Tingjun Hou, Junmei Wang
May 30, 2009·Toxicology Letters·Klaus SchneiderSebastian Hoffmann
Jun 13, 2009·Combinatorial Chemistry & High Throughput Screening·Tingjun HouJunmei Wang
Jun 23, 2009·SAR and QSAR in Environmental Research·J C DeardenK L E Kaiser
Jun 25, 2010·Journal of Chemical Information and Modeling·Denis FourchesAlexander Tropsha
Sep 3, 2010·Journal of Cheminformatics·Barry HardySylvia Escher
Apr 8, 2011·Combinatorial Chemistry & High Throughput Screening·Jingyu ZhuTingjun Hou
Apr 15, 2011·Journal of Chemical Information and Modeling·C M EllisonP N Judson
Apr 11, 2012·International Journal of Molecular Sciences·Katharine BriggsJörg D Wichard
Apr 18, 2012·SAR and QSAR in Environmental Research·K R PrzybylakM Hewitt
May 14, 2014·Journal of Chemical Information and Modeling·Pau CarrióManuel Pastor
Jun 10, 2014·Journal of Cheminformatics·Villu RuusmannUko Maran
Jun 29, 2014·Journal of Molecular Modeling·Bernd Beck, Tim Geppert

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