Figure 3

Within-arm and between-arm analyses for primary endpoints at 6-weeks. The mean differences in THI and TFI scores across participants for arm 1 and arm 2 from baseline to 6-week assessment for the within-arm cases, or the mean differences between arm 1 and arm 2 for the change in scores from enrollment to 6-week assessment for the between-arm cases are plotted with the ± 95% CI. Within-arm analyses were based on per-protocol analysis that included treatment-compliant participants (≥ 18 h treatment at 6-weeks) with baseline and 6-week scores. The baseline score corresponds to the average of the scores at screening and enrollment visits. Within-arm analyses for arm 1 and arm 2 showed a highly statistically significant reduction in THI and TFI scores (i.e., improvement in tinnitus symptom severity) based on paired two-tailed t-tests (P < 0.0001; 95% CI does not overlap the vertical line at zero). Between-arm analyses were conducted using an intention-to-treat analysis with changes in THI or TFI scores from the enrollment to 6-weeks assessment and tested with multiple regression using enrollment score as a covariate. Missing data were imputed using the Markov chain Monte Carlo multiple imputation method (further details are provided in the Methods), which leads to n values that match the enrolled numbers for each arm. There was no significant difference between arm 1 and arm 2 (P > 0.05; 95% CI crosses vertical line at zero). Note that primary endpoint analyses included within-arm changes for THI and TFI for arm 1 and between-arm differences for arm 1 and arm 2 only for THI, but that the other within-arm and between-arm comparisons are presented in this figure for completeness. Parameter settings (see Supplementary Table S1 for details): arm 1—PS1 (synchronized bimodal stimulation, includes pure tones and background noise stimuli); arm 2—PS6 (includes only pure tones with no background noise stimuli and with varied interstimulus delays in the range of 700–800 ms).