The audiogram: Detection of pure-tone stimuli in ototoxicity monitoring and assessments of investigational medicines for the inner ear

Abstract

Pure-tone thresholds have long served as a gold standard for evaluating hearing sensitivity and documenting hearing changes related to medical treatments, toxic or otherwise hazardous exposures, ear disease, genetic disorders involving the ear, and deficits that develop during aging. Although the use of pure-tone audiometry is basic and standard, interpretation of thresholds obtained at multiple frequencies in both ears over multiple visits can be complex. Significant additional complexity is introduced when audiometric tests are performed within ototoxicity monitoring programs to determine if hearing loss occurs as an adverse reaction to an investigational medication and during the design and conduct of clinical trials for new otoprotective agents for noise and drug-induced hearing loss. Clinical trials using gene therapy or stem cell therapy approaches are emerging as well with audiometric outcome selection further complicated by safety issues associated with biological therapies. This review addresses factors that must be considered, including test-retest variability, significant threshold change definitions, use of ototoxicity grading scales, interpretation of early warning signals, measurement of notching in noise-induced hearing loss, and application of age-based normative data to interpretation of pure-tone thresholds. Specific guidance for clinical trial protocols that will assure rigorous methodological approaches and interpretable audiometric data are provided.

U.S. Population Data on Hearing Loss, Trouble Hearing, and Hearing-Device Use in Adults: National Health and Nutrition Examination Survey, 2011–12, 2015–16, and 2017–20

“…Audiograms have long been obtained using standardized psychophysical procedures and precisely calibrated equipment to ensure the accuracy and reliability of the measurements across time and across clinics ( Bunch, 1922 , 1943 ; Carhart & Jerger, 1959 ). LePrell et al (2022) provide a recent description of the history of pure-tone audiometry and its application to several clinical disorders, including noise-induced hearing loss and ototoxicity-induced hearing loss.…”

Evaluation of hidden hearing loss in normal-hearing firearm users

“…Therefore, more recent approaches have included the exploration of hearing-in-noise function (performance) for possible associations with measures of OHC function (typically assessed using DPOAEs) and/or measures of neural function using evoked potentials, such as the auditory brainstem response (ABR), acoustic reflex threshold/middle ear muscle reflex (MEMR), or envelope following response (EFR) (Grant et al, 2020;Mepani et al, 2020Mepani et al, , 2021Parker, 2020; 10.3389/fnins.2022.1005148 Shehorn et al, 2020;Bramhall et al, 2022). At present, the audiogram remains the gold standard clinical tool in audiology (for recent review see Le Prell et al, 2022), but there is universal agreement that clinical dysfunction can be "hidden" beyond a normal audiogram (i.e., "hidden hearing loss"; see Schaette and McAlpine, 2011).…”

Effects of Stimulus Type on 16-kHz Detection Thresholds

“…In the current dataset, the largest difference between 16-kHz thresholds obtained with steady and FM tones was 20 dB. This effect size exceeds the 10-dB criterion often adopted when evaluating whether changes in threshold following exposure to noise or ototoxic agents are clinically meaningful (Le Prell et al 2022; OSHA 2022). A difference in sensitivity of this magnitude between 15.2 and 16 kHz implies that the audibility curve for these participants is quite steep, more than 100 dB per octave.…”