Value of shared preclinical safety studies - The eTOX database.
A first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented. Species, duration of exposure and administration route data were analysed to assess if large enough subsets of homogenous data are available for building in silico predictive models. Prevalence of treatment related effects for the different types of findings recorded were analysed. The eTOX ontology was used to determine the most common treatment-related clinical chemistry and histopathology findings reported in the database. The data were then mined to evaluate sensitivity of established in vivo biomarkers for liver toxicity risk assessment. The value of the database to inform other drug development projects during early drug development is illustrated by a case study.
['Briggs|Katharine|K|', 'Barber|Chris|C|', 'Cases|Montserrat|M|', 'Marc|Philippe|P|', 'Steger-Hartmann|Thomas|T|']
Ontology Biomarkers ALP, alkaline phosphatase ALT, alanine aminotransferase AST, aspartate aminotransferase CDISC, Clinical Data Interchange Standards Consortium CRO, contract research organisation DILI, drug induced liver injury Data mining Data sharing EFPIA, European Federation of Pharmaceutical Industries and Associations FN, false negative FP, false positive GLP, good laboratory practice ICH, International Conference on Harmonisation IMI, Innovative Medicines Initiative INHAND, International Harmonization of Nomenclature and Diagnostic Criteria IT, information technology MCC, Matthews correlation coefficient OECD, Organisation for Economic Co-operation and Development PDF, Portable Document Format PDF/A, ISO-standardized version of PDF specialized for the digital preservation of electronic documents. QA, quality assurance SEND, Standard for Exchange of Nonclinical Data SME, small-to-medium enterprise TN, true negative TP, true positive Toxicology ULN, upper limit of normal eTOX, integrating bioinformatics and chemoinformatics approaches for the development of expert systems allowing the in silico prediction of toxicities