title: EEG in non-clinical drug safety assessments: Current and emerging considerations.
abstract: Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations. In the current paper, we discuss the various aspects of preclinical EEG to characterize drug-induced seizure risk and sleep disturbances, as well as describe the use of these data in a regulatory context. An overview of EEG technology-its correct application and its limitations, as well as best practices for setting up the animal models is presented. Sleep and seizure detection are discussed in detail. A regulatory perspective on the use of EEG data is provided and, tying together the previous topics is a discussion of the translational aspects of EEG.
authors.affiliation: CiToxLAB North America, 445 Armand Frappier, Laval, QC H7V 4B3, Canada. Electronic address: authiers@ca.citoxlab.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: Division of Anesthesia, Analgesia and Addiction Products (DAAAP), CDER, U.S. Food & Drug Administration, Silver Spring, MD, USA.
authors.forename: Marcus S
authors.initials: MS
authors.lastname: Delatte
authors.affiliation: Kallman Preclinical Consulting, Greenfield, IN 46140, USA.
authors.forename: Mary-Jeanne
authors.initials: MJ
authors.lastname: Kallman
authors.affiliation: Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Safety Assessment, Merck Research Laboratories, Kenilworth, NJ 07033, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Markgraf
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data; D006801:Humans; D017286:Polysomnography; D012449:Safety; D012890:Sleep / Q000187:drug effects*
keywords: Convulsion; EEG; Neurotoxicity; Polysomnography; Safety pharmacology; Seizure; Sleep; Spike; Telemetry