Approach to Neurosafety
There is not a single approach to all neurologic safety testing needs. Rather, a toolset of approaches exists from which each safety assessment study can choose the tools most appropriate to the study.
Behavioral vs. Pathological Assessments
Behavioral test and pathologic tests each have their own unique strengths and challenges. These are complementary approaches in the realm of safety testing and should both be employed in a manner suited to each.
Spectrum of Pathologic Endpoint Detection
Unfortunately, there is not a single endpoint that is both valid and comprehensive to meet the needs of all pathologic safety evaluations. Rather, there is a spectrum of safety considerations in the pathology of the brain. At one end of the spectrum, there are no detectable changes to the Central Nervous System (CNS) (safe) and at the other end of the spectrum are permanent changes to the CNS (unsafe). In between these two extremes, for example, are detectable changes in chemistry, neurotransmitter responses and perturbations leading to an inflammatory response. In the illustration below, the farther a change falls to the right of the spectrum of changes, the more serious is the concern that change represents from a safety perspective. At the left end of the spectrum (i.e., chemistry changes), there are many potential pathologic endpoints from which to choose. Moving to the right (unsafe) side of the spectrum, the number of detection methods decreases and endpoints are more specific and definitive as a safety concern. While each safety study has different approaches, the best designs include evaluation of a selected point on this spectrum as well as assessments to the right of that point. Many designs focus on just the most conclusive endpoint of permanent damage at the far right of the spectrum.
A successful safety study must first determine the scope of changes to be evaluated, then choose the methods appropriate to evaluate those chosen endpoints.
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