Designing Validation Studies More Efficiently According to the Modular Approach: Retrospective Analysis of the EPISKIN Test for Skin Corrosion

Sebastian Hoffmann and Thomas Hartung

It is claimed that the modular approach to validation, which involves seven independent modules, will make the assessment of test validity more flexible and more efficient. In particular, the aspects of between-laboratory variability and predictive capacity are formally separated. Here, the main advantage of the approach is to offer the opportunity for reduced labour, and thus to allow study designs to be more time efficient and cost effective. The impact of this separation was analysed by taking the ECVAM validation study on in vitro methods for skin corrosivity as an example of a successful validation study — two of its methods triggered new OECD test guidelines. Lean study designs, which reduced the number of tests required by up to 60%, were simulated with the original validation data for the EPISKIN™ model. By using resampling techniques, we were able to demonstrate the effects of the lean designs on three between-laboratory variability measures and on the predictive capacity in terms of sensitivity and specificity, in comparison with the original study. Overall, the study results, especially the levels of confidence, were only slightly affected by the lean designs that were modelled. It is concluded that the separation of the two modules is a promising way to speed-up prospective validation studies and to substantially reduce costs, without compromising study quality.
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