The importance of the prediction model in the validation of alternative tests

An overview is presented of the validation process adopted by the European Centre far the Validation of Alternative Methods. with particular emphasis on the central role of the prediction model (PM). The development of an ade quate PILI is considered to be just as important as the development of an a dequate test system, since the validity uf an alternative test can only be established when both components (the test system and the PM) have successf ully undergone validation. It is argued, however, that alternative tests an d their associated PMs do not necessarily need to undergo validation at the same time, and that retrospective validation may be appropriate when a tes t system is found to be reliable, hut the case for its relevance remains to be demonstrated. For an alternative test to be considered "scientifically valid", it is necessary for three conditions to be fulfilled, referred to h ere as the criteria for scientific relevance, predictive relevance, and rel iability. A minimal get of criteria for the acceptance of any PM is defined , but it should be noted that required levels of predictive ability need to be established on a case-by-case basis, taking into account the inherent v ariability of the alternative and in vivo test data. Finally, in view of th e growing shirt in emphasis from the use of stand-alone alternative tests t o alternative testing strategies. the importance of making the PM an integr al part of the testing strategy is: discussed.