title: Utility of the auditory brainstem response evaluation in non-clinical drug safety evaluations.
abstract: BACKGROUND
  The Food and Drug Administration (FDA) requires thorough evaluation of the potential safety hazards of all new drugs, food additives, and therapeutic devices that are intended for human use. Drugs that are otically administered (i.e., ear drops), or are known to systemically distribute to the inner ear, require additional specialized safety testing to ensure that the drug does not permanently impair auditory function.
  
  
  METHODS
  To properly determine a drug's impact on auditory function, the FDA's Center for Drug Evaluation and Research requires the use of the Auditory Brainstem Response (ABR) evaluation. The ABR evaluation uses auditory stimuli evoked potentials to assess function by establishing minimum intensity thresholds. These thresholds can be monitored following drug treatment to determine an impact on hearing loss. This review discusses methodical considerations for conducting ABR evaluations as they apply to specialized drug safety studies. Alternative assays are discussed and compared to the utility of the ABR evaluation.
  
  
  CONCLUSIONS
  The ABR evaluation provides reliable and sensitive measures of hearing function that are suitable for definitive drug safety evaluations or hazardous risk assessments.
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: 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: 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. 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*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
keywords: Auditory brainstem response evaluations; Auditory function; Drug safety; Drug-induced hearing loss; Method; Ototoxicity; Risk assessment