## 4 Discussion
### Advanced DPOAE Paradigm Comparisons (Frequency, Level, and Ratio Sweeps--Group Delays)  
In this paper, we demonstrate the clinical applicability of advanced DPOAE measurement hardware and paradigms. It is all too common that data obtained on typical clinical equipment results  
Figure 6: Case illustration of an adult undergoing cisplatin therapy (Exposed; left; a; c; same patient as Figure 5) compared to age-matched control subject (Control; right; b; d) for serial measurement of DPOAEs over 3 trials, averaging 3 weeks apart. DPOAE levels recorded for full bandwidth of f\({}_{2}\) frequencies (0.8 to 20 kHz; 1/8 octave step; 1.22; 6/52 dB FPL; top; a; b) versus limited bandwidth (8 to 20 kHz; bottom; c; d) using standard stimulus parameters. The solid lines with black triangles represent trial 1 (baseline) prior to exposures and the long-dashed lines with red squares or gray diamonds represent trials 2 and 3 (monitoring visits), respectively, for the exposed individual with trials 1–3 for the control individual matched for testing in chronological time. The short-dashed lines without symbols are the average noise floor for all trials for the respective individual. The line at \(-\)20 dB SPL plotted as a reference for visual comparison. in very limited (or no) information at baseline in \"real world\" applications in adult patients. This is a challenge when baseline information is necessary to monitor for the care of the patient. Employing advanced hardware and calibration techniques permitting higher frequency and higher intensity stimuli to be delivered permits a broader range of clinical information than traditional approaches. Results supportotoxic changes can be detected and monitored successfully by utilizing DPOAE measurements \(>\)8 kHz when suitable hardware/signal delivery capabilities, calibration techniques, and stimulus parameters are employed [16; 21; 28; 29; 30; 31; 48]. Here, we report clinically-defined significant changes that were often noted at frequencies higher than conventionally tested. When examining the patient data presented in the Results section (refer to Table 3), no significant change for any paradigm tested during serial monitoring was demonstrated for one case (patient 3). Upon further investigation, this patient was the oldest, only had measurable DPOAEs out to 3 kHz for monitoring, and passed away after the second monitoring session. It is unknown if significant changes would have occurred had monitoring continued. Only two monitoring sessions were obtained for patient 12 before passing away. The only significant change for patient 12 with measurable DPOAEs out to 6 kHz occurred in the L\({}_{1}\) fixed and L\({}_{2}\) varied paradigm at the second highest frequency monitored. Patient 2 only had one significant change, which occurred in the high-level concentrated sweep paradigm. The highest DPOAE frequency for monitoring was 5.3 kHz and only two sessions were completed for patient 2. All other patients (n = 9) had a minimum of three significant changes for the analyses completed (n = 11) and one patient (9) had significant changes in all analyses, with the exception of group delays calculated at the second highest frequency. The percentage of patients with a significant change for the various analyses ranged from 33% for group delays at the second highest frequency to 90% for the L\({}_{1}\) fixed and L\({}_{2}\) varied at the second highest frequency. The patients that had a significant change in the gross frequency sweep also had a significant change in the mid-level concentrated sweep and given the gross frequency sweep was conducted initially to determine what frequencies could be monitored, it is not clear that measuring the mid-level concentrated sweep was valuable in this patient population. The greatest number of patients demonstrating significant changes occurred for the high-level concentrated sweep and the L\({}_{1}\) fixed with L\({}_{2}\) varied at the second highest frequency monitored.