Legacy data sharing to improve drug safety assessment: the eTOX project

Non-clinical safety assessment is often faced with the challenge of assessing candidate compounds with no or insufficient experimental data. Whereas relevant databases and reliable in silico tools exist for mutagenicity prediction, analogous resources for identifying potential organ toxicities are not as common or well developed. Scientists, therefore, have to resort to suboptimal procedures such as literature search and personal experience with similar compounds or classes. In parallel, there is a wealth of relevant data buried in the archives of the pharmaceutical industry that has not yet been leveraged. These data mainly exist in paper or pdf formats and, consequently, are difficult to search and analyze. In order to overcome these limitations and advance early safety assessment, 13 pharmaceutical companies, 11 academic partners and 6 small and medium-sized enterprises (SMEs) joined forces in the eTOX project, which started in January 2010 under the sponsorship of the European Innovative Medicines Initiative (IMI). Since the availability of a wide and representative collection of historical data is fundamental for generating reliable predictions, the main goals of the eTOX project were (i) to build a shared and mineable database containing a broad and relevant collection of data, constituted mainly by repeat-dose toxicity studies contributed by the pharmaceutical companies participating in the project, and (ii) to use the database and other sources of information for enabling more effective read-across and predictive modeling of safety endpoints