title: The failure to detect drug-induced sensory loss in standard preclinical studies.
abstract: Over the years a number of drugs have been approved for human use with limited signs of toxicity noted during preclinical risk assessment study designs but then show adverse events in compliant patients taking the drugs as prescribed within the first few years on the market. Loss or impairments in sensory systems, such as hearing, vision, taste, and smell have been reported to the FDA or have been described in the literature appearing in peer-reviewed scientific journals within the first five years of widespread use. This review highlights the interactive cross-modal compensation within sensory systems that can occur that reduces the likelihood of identifying these losses in less sentient animals used in standard preclinical toxicology and safety protocols. We provide some historical and experimental evidence to substantiate these sensory effects in and highlight the critical importance of detailed training of technicians on basic ethological, species-specific behaviors of all purpose-bred laboratory animals used in these study designs. We propose that the time, effort and cost of training technicians to be better able to identify and document very subtle changes in behavior will serve to increase the likelihood of early detection of biomarkers predictive of drug-induced sensory loss within current standard regulatory preclinical research protocols.
authors.affiliation: 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: MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA. Electronic address: matthew.abernathy@mpiresearch.com.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Abernathy
authors.affiliation: MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA. Electronic address: rachel.tapp@mpiresearch.com.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Tapp
authors.affiliation: MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA. Electronic address: joshua.yoder@mpiresearch.com.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Yoder
authors.affiliation: MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Dalton
authors.affiliation: MPI Research, 54943 North Main Street, Mattawan, MI 49071, USA. Electronic address: theodore.baird@mpiresearch.com.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Baird
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D006801:Humans; D018570:Risk Assessment; D012449:Safety; D012677:Sensation / Q000187:drug effects*; D012678:Sensation Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D011984:Sensory Receptor Cells / Q000187:drug effects*
keywords: Ageusia; Anosmia; Auditory function; Drug safety; Drug-induced sensory loss; Method; Ototoxicity; Quality of life; Risk assessment; Treatment adherence