Validazione Retrospettiva: per valutare al meglio i metodi alternativi serve una validazione migliore

[Hartung T. Evidence-based toxicology – the toolbox of validation for the 21st century? ALTEX. 2010;27(4):253-63.]

Full Text:


Validation has become a primary driver of the evolution of toxicological methods. Agreement at OECD level currently requires validation of new approaches for consideration in test guideline development. Several examples of this exist. However, the toxicology in the 21st century movement, prompted by the 2007 NRC/NAS vision document, might lead to a revolutionary change in the toxicological toolbox. The challenge is whether the validation process, as it has been formalized over the last two decades, meets the needs for this paradigm shift. 

The concept of evidence-based medicine (EBM) has emerged from clinical medicine, which retrospectively assesses the evidence of adequacy of a given approach. This is not typically done in prospective studies – the equivalent of validation studies might be multicenter randomized trials. Evidently, where such unambiguous evidence is available, no other assessment is necessary. EBM, however, has developed procedures, including meta-analysis, to collect and evaluate all the available evidence where no such definitive study is available. The recent successful introduction of retrospective validation, i.e. the collection and evaluation of existing evidence from various sources, represents a step in this direction. Here, we will explore new toxicological approaches via evidence-based toxicology (EBT).

Nel testo:

“1. Traditional validation allows only substituting a method with something similar and does not accommodate paradigm shifts due to its comparison to the traditional test. The predictivity of a test approach can thus not be changed.
2. The pressing need to renovate methods for regulatory toxicology calls for information-rich, complex methods. These represent a challenge for quality assurance (such as GLP) and validation. While test definition and reproducibility can be handled similarly, scientific relevance will need to be stressed to compensate for the difficult predictive relevance in the absence of a reference test.
[…] 4. We need to develop meta-analysis tools for retrospective validation and EBT. They will be most useful for the risk assessment process for individual compounds, where several studies are available. For this purpose, the quality score concept for toxicological studies needs to be further developed.”



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