Curation and analysis of clinical pathology parameters and histopathologic findings from eTOXsys, a large database project (eTOX) for toxicologic studies

Large data sharing projects amongst the pharmaceutical industry have the potential to generate new insights using data on a scale that has not been previously available. A retrospective analysis of the preclinical toxicology data collected as part of the eTOX project was conducted with the aim to provide background rates and treatment-related value analysis on both clinical pathology and histopathology datasets. Incorporated into this analysis was an extensive data consolidation task to standardise all data. Reference intervals for common clinical pathology parameters in rat and dog were generated, alongside background histopathology incidence rates in the liver, heart and kidney. Systematically applied decision thresholds allowed consistent relabelling of data points considered anomalous, and maximum fold change estimates. Relabelling of anomalous data points was conducted for the histopathology data using a Bayesian model to identify dose-dependent increases in pathologies. The results of this study allow: newly generated data to be analysed using the same methodology, rates and distributions to be used when building predictive dose-response models, and the possibility to correlate clinical pathology findings with concurrent histopathology findings. In the first half of this paper we discuss data curation, in the second half we report on the analytical methods and results.