Abstract
The absence of activity may represent either a true or false negative effect. If an assay is valid for the particular test article and fails to indicate activity, it is an appropriate indicator of future events. However, if the assay is insensitive or incapable of response, the test represents a form of bias, albeit unconscious. Many biological products demonstrate a specificity of response that limits the utility of commonly employed safety studies. Specificity for many biologies arises from both their physicochemical properties and their similarity to endogenous substances which are regulated in a carefully controlled manner. To overcome the issue of a lack of predictive value, various approaches may be used. For example, a multiple testing strategy of mutually reinforcing studies may be employed or safety studies may be adoptively fit to the biological circumstance.