title: 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.
authors.affiliation: Department of Neurobehavioral Sciences, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA. Electronic address: david.gauvin@mpiresearch.com.
authors.forename: David V
authors.initials: DV
authors.lastname: Gauvin
authors.affiliation: Department of Neurobehavioral Sciences, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Yoder
authors.affiliation: Department of Safety Pharmacology, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Holdsworth
authors.affiliation: Department of Safety Pharmacology, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Marci L
authors.initials: ML
authors.lastname: Harter
authors.affiliation: Department of Safety Pharmacology, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Jonelle R
authors.initials: JR
authors.lastname: May
authors.affiliation: Department of Safety Pharmacology, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Noelle
authors.initials: N
authors.lastname: Cotey
authors.affiliation: Department of Safety Pharmacology, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Dalton
authors.affiliation: Department of Drug Safety Evaluation, MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Baird
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000523:psychology; D051381:Rats; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
keywords: Age; Behavior analysis; Circadian rhythms; Ethology; FOB; Functional changes; Functional observational battery; Gender; Phylogeny; Rat; Strain differences