The standardized functional observational battery: Its intrinsic value remains in the instrument of measure: The rat

Abstract

The International Conference on Harmonisation's (ICH) Tripartite Guideline on Safety Pharmacology Studies for Human Pharmaceuticals has adopted the requirement that each new test substance must be tested for effects on the central nervous system prior to "first dose in man". This assessment is required to measure, at a minimum, the effects of the substance on general motor activity, behavioral changes, coordination, sensory/motor reflex responses, and body temperatures. To achieve this goal, ICH S7A recommends a neurobehavioral assessment (usually a functional observational battery (FOB) or modified Irwin test), which is generally undertaken in the rat. There seems to be a growing lack of consensus on the value of the FOB to determine CNS safety. This review highlights the importance of the time, effort and cost of training technicians to familiarize with their instrument of measure, so that each observer is better able to identify and document very subtle changes in behavior that will serve to increase the reliability and validity of these assays with respect to CNS safety assessments.

Keywords: Age; Behavior analysis; Circadian rhythms; Ethology; FOB; Functional changes; Functional observational battery; Gender; Phylogeny; Rat; Strain differences.