Evaluation of the CR Neuromodulation Treatment for Tinnitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the CR Neuromodulation Treatment for Tinnitus (NCT01541969), a randomized phase 2, phase 3 study. The primary outcome is Tinnitus Handicap Questionnaire (THQ).

2. Clinical Question

The study’s stated aim was to evaluate whether acoustic coordinated reset neuromodulation has clinical benefit for people with intrusive tinnitus. Its proposed mechanism—that the sound pattern might disrupt synchronized nerve firing thought to be related to tinnitus—is a hypothesis in the registry description, not a result established by the posted outcome data. The registry also describes measuring brain activity in a subset of participants.

The primary endpoint focuses on the functional impact of tinnitus as measured by the THQ. The comparison is between two device conditions rather than between device use and no device: both groups were assigned the same device, while the comparator device was not programmed with the therapeutic algorithm. The registry record does not report further details about how participants experienced the masking condition or how successful masking was.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group study with phase listed as PHASE2 and PHASE3. It is marked completed, with enrollment of 100. The study start is recorded as 2012-08 and primary completion as 2014-02. Nottingham University Hospitals NHS Trust is listed as the sponsor.

Participants were assigned to CR Neuromodulation or Tinnitus Masking. The CR arm used the Adaptive NeuroModulation T30 CR Neurostimulator according to the manufacturer/funder training given to the study team. The masking arm used the same device, but it was not programmed according to the therapeutic algorithm for 0-12 weeks. The record identifies the design as randomized, double-masked and parallel, but does not report further details about the masking procedures or allocation implementation.

The primary outcome was mean change in the global Tinnitus Handicap Questionnaire score between baseline (visit 2) and 12 weeks (visit 6). The primary outcome population is described as complete-case data, although the study also analyzed multiple-imputed data; only complete-case results are reported for this endpoint. The primary comparison includes 42 participants in the CR Neuromodulation group and 44 in the Tinnitus Masking group.

The registry lists other outcomes relating to tinnitus handicap and function, quality of life, and EEG brainwave activity. Detailed numerical comparisons are posted for three secondary outcomes. The record does not give the original design’s sample-size assumptions, detailed allocation methods, or a fuller statistical analysis plan. Those omissions limit how completely the planned design and analysis can be reconstructed from the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 217 screen fails: Ménière(6), neuroma(2), TMJ(3), hearing loss(2), new hearing-aid user(11), recent hearing-aid adjustments(2), severe anxiety(4), severe depression(5), pulsatile TI(7), somatic TI(17), intermittent TI(7), slight TI(35), catastrophic TI(6), pitch match not possible(7), pitch out of fitting range(56), prescription tones inaudible(47)

Double-blind (0-12 Weeks)

Reasons for not completing this period:

Open Label Extension (12-36 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: We have analyzed both complete case and multiple imputed data for the mean change in global THQ score from baseline (visit 2) to 12 weeks (visit 6). Here we report complete case data.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Tinnitus Handicap Questionnaire (THQ), measured over Baseline (visit 2) and 12 weeks (visit 6).

The primary endpoint is change in the global score of the Tinnitus Handicap Questionnaire, a 27 item, multi-attribute measure of the functional impact of tinnitus. The scale ranges from 0-100. The registry defines change as the score at baseline (visit 2) minus the score at 12 weeks (visit 6). Under that definition, a positive change score indicates a reduction in tinnitus symptoms; it should not be confused with a 12-week score minus baseline, which would reverse the direction.

The THQ is used to represent the impact of tinnitus on functioning, rather than to measure a biological mechanism directly. That makes it relevant to the study’s stated clinical question about the effect of the device intervention on people’s experience of tinnitus. The primary endpoint is continuous, and the posted summaries report group means and standard deviations.

The endpoint description establishes what was measured and the direction of its change score, but it does not state a threshold for a clinically important difference. Such a threshold is not reported in the registry record. Therefore, the size of the group difference can be described in THQ units, but the registry information does not establish whether a particular difference would be important to participants.

7. Results Posted in the Registry

• Tinnitus Masking: mean 4.02 versus 3.75 on control; difference 0.27 (95% CI -4.64 to 5.18), standardized effect d = 0.02; z-test p = 0.914.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Tinnitus Handicap Inventory (THI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tinnitus Masking: mean 1.64 versus 2.84 on control; difference -1.20 (95% CI -6.66 to 4.26), standardized effect d = -0.09; z-test p = 0.666.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tinnitus Masking and the control. The interval gives the range of effects that remain compatible with the data.

Tinnitus Functional Index (TFI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tinnitus Masking: mean 4.45 versus 2.38 on control; difference 2.07 (95% CI -5.24 to 9.38), standardized effect d = 0.12; z-test p = 0.579.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tinnitus Masking and the control. The interval gives the range of effects that remain compatible with the data.

World Health Organization Quality of Life Questionnaire (WHOQOL-BREF)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tinnitus Masking: mean -0.11 versus -0.21 on control; difference 0.10 (95% CI -0.16 to 0.36), standardized effect d = 0.16; z-test p = 0.453.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tinnitus Masking and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover related but not identical aspects of tinnitus and health: tinnitus handicap, tinnitus functional impact, quality of life and EEG brainwave activity are among the outcomes listed in the registry. Numerical group comparisons are posted for THI, TFI and WHOQOL-BREF. Their estimates are modest in relation to their uncertainty, and their confidence intervals include zero. This broad pattern is consistent with the primary THQ comparison: the posted data do not give a precise separation between the two groups at 12 weeks.

Secondary measures can add context to a primary endpoint by showing whether a pattern is similar across different instruments or domains. Agreement across measures can be informative, but it does not independently confirm a treatment effect, particularly when the estimates are uncertain and the outcomes are related. Differences between measures may also reflect that each instrument captures a distinct construct, uses its own scale and has its own variability.

The registry lists five secondary outcomes, but detailed numerical comparisons are not reported in the registry record for every listed measure. In particular, detailed numerical EEG results are not present in the posted outcome comparisons. The registry lists the Tinnitus Handicap Questionnaire among secondary outcomes as well as identifying it as the primary endpoint; the primary complete-case comparison is the detailed THQ result discussed separately.

Unadjusted secondary results carry less weight because testing multiple outcomes increases the chance of observing an apparently unusual result by chance. The registry record does not report a multiplicity adjustment, an outcome hierarchy or a plan for interpreting secondary tests. Accordingly, the secondary results are best regarded as supporting context rather than independent confirmatory evidence. They do not change the central limitation of the primary comparison: its confidence interval is compatible with effects in either direction.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Tinnitus Handicap Inventory (THI)
• Tinnitus Functional Index (TFI)
• World Health Organization Quality of Life Questionnaire (WHOQOL-BREF)
• Percent Change From Baseline in Normalized Oscillatory Power in the Delta Brainwave Pattern as Measured by Electroencephalography (EEG)
• Tinnitus Handicap Questionnaire (THQ)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measure, so its group summaries are means, accompanied by standard deviations. A mean describes the average change score in a group. A standard deviation describes how dispersed individual scores are around that group mean. It is not the uncertainty of the mean itself: uncertainty in the estimated group mean also depends on the number of observations contributing to it.

The comparison is a difference between group means. The displayed estimate is oriented as Tinnitus Masking minus CR Neuromodulation. A positive value therefore means the masking group had the larger mean change score; because the endpoint defines positive change as reduced symptoms, this direction corresponds to a larger average reduction in the masking group. A negative value would indicate a larger average change in the CR group. These are directions of the numerical contrast, not proof of a meaningful or causal advantage.

A confidence interval expresses uncertainty around an estimated difference. Its endpoints indicate a range of values compatible with the observed data under the assumptions of the interval method. Intervals that include zero do not establish that the true difference is exactly zero. Rather, they indicate that the data do not distinguish zero from the range of positive and negative differences covered by the interval. The reported primary interval runs from -4.643 to 5.183, so the estimate is not precise enough to rule out differences in either direction.

The registry posts an unadjusted p-value of 0.914 for the primary comparison. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The registry record does not report the detailed test or model used for the original sponsor analysis. The posted comparison is a simple unadjusted comparison based on summary statistics, not a substitute for an analysis that adjusts for covariates or uses participant-level data.

The complete-case population means that the reported primary result uses participants with the data required for that analysis. The registry says multiple-imputed data were also analyzed, but reports complete-case results for this endpoint. Multiple imputation is a general statistical approach that replaces missing values with plausible values drawn from a model, while representing uncertainty in those replacements. The registry record does not report the imputation model, variables used, assumptions about missingness, or the result from that analysis. Consequently, its robustness to missing data cannot be evaluated from the posted primary result alone.

Over-dispersion is a general concern when variability is greater than an analysis model expects. For continuous outcomes, a large standard deviation relative to the mean contrast can make estimates less precise. The primary outcome summaries show substantial spread compared with the estimated mean difference, but the registry record does not report a model-based assessment of over-dispersion, and it should not be assumed that such a model was used.

Randomization is intended, in general, to make treatment groups comparable on average at the start of a study, including on factors that were not measured. The record identifies this study as randomized, but does not report the allocation sequence method, concealment procedure, or baseline balance details in the information summarized for this comparison. Double masking is recorded, but the people masked and the procedures used are not reported. These design labels alone do not supply the missing operational details.

The posted secondary comparisons also report group means, mean differences, confidence intervals and unadjusted p-values. In general, examining multiple outcomes creates more opportunities for apparently notable findings by chance. A multiplicity adjustment or a prespecified hierarchy can address that issue, but the registry record does not report whether either was planned or used. The secondary results should therefore be considered exploratory unless additional analysis information is available.

The planning illustrations use a normal approximation, equal allocation between arms and a two-sided significance level of 0.05. They are based on fractions of the observed effect. These are planning assumptions for those illustrations, not a description of the original trial’s design calculations. The original sample-size justification and trial analysis plan are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is 0.27 THQ units, with a 95% confidence interval from -4.643 to 5.183. This interval is wide in relation to the estimate and includes zero. It also spans values in both directions, so the data do not precisely determine which group had the larger mean change. In particular, the small positive point estimate should not be interpreted on its own as a reliable difference between the device conditions.

In general, a confidence interval gives an indication of the range of effect sizes that are reasonably compatible with the data and the method used to calculate the interval. It does not give a guarantee that the true effect lies within those particular endpoints, nor does it show the probability that an individual participant will experience a particular change. Here, the interval is for a difference between group means, not for individual THQ scores.

The observed group standard deviations, 13.29 and 9.56, are notably larger than the estimated contrast. That variation helps explain why the estimate is imprecise: individual change scores vary substantially around the group averages, while the estimated average difference is close to zero. The complete-case group sizes contributing to the comparison were 42 and 44. The registry does not report the number of missing primary outcomes or the multiple-imputation result, so precision and potential selection effects in that analysis cannot be compared with an alternative missing-data analysis.

The interval does not determine clinical importance because a threshold for a meaningful THQ difference is not reported in the registry record. It also does not resolve longer-term effects; the primary outcome comparison concerns baseline and 12 weeks. The most defensible reading is that the estimated difference is small, but uncertainty remains about the direction and size of any underlying average contrast.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations, not the sample size used to conduct the trial. For these continuous outcomes, the figures are participants per arm, not total participants. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They calculate the number of participants per arm for detecting the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes a planning scenario in which a study of the indicated size would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect were real and the assumptions held. The 90% power column uses a higher target chance of detection and therefore generally requires more participants. Neither column describes the probability that the observed trial result is correct.

Rows for 100%, 75% and 50% of the observed effect show how the calculation changes when the target effect is set to a different fraction of the observed estimate. Smaller effects are harder to detect against background variation, so planning for a smaller effect requires more participants per arm. The observed primary mean difference is close to zero; calculations based on a very small observed effect can consequently produce very large planning figures. These estimates should not be treated as a recommendation for a future study without a scientifically justified target effect and design.

The figures are not observed power. Observed power is not a useful substitute for interpreting the estimate and its confidence interval; the interval communicates the uncertainty in the primary comparison more directly. The sample-size illustrations instead describe hypothetical planning under their stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.270; pooled standard deviation σ = 11.532.
2. n = 2 × (1.96 + 0.842)² × 11.532² / 0.270² = 28,638.0, rounded up to 28,639 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.27                      # observed difference in means
sigma <- 11.5323111816529                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1541969)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 28,639 (80% power), 38,339 (90% power)
 75% of observed effect: n per arm = 50,913 (80% power), 68,157 (90% power)
 50% of observed effect: n per arm = 114,553 (80% power), 153,353 (90% power)
power.t.test: 28639 
Simulated power at n = 28,639 per arm: 0.804 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary endpoint and lists multiple secondary outcomes. Considering several outcomes and analyses can increase the chance of a nominally unusual result even when there is no true effect. Statistical approaches such as adjusting significance thresholds, controlling an error rate, or specifying a hierarchy of outcomes can address multiplicity. Whether any such approach was planned or used is not reported in the registry record. The posted comparisons include unadjusted p-values, so they should not be treated as multiplicity-adjusted evidence.

The primary outcome description states that both complete-case and multiple-imputed data were analyzed, but only complete-case data are reported. The record does not report the multiple-imputation estimate, imputation procedure, assumptions about missingness, or sensitivity analyses. It also does not report how many primary outcome values were missing or why. As a result, readers cannot assess from the registry record whether the complete-case analysis and imputed analysis gave similar conclusions, or how missing outcomes may have affected the estimate.

The primary comparison includes 42 participants in the CR Neuromodulation group and 44 in the Tinnitus Masking group. These are the analysis counts for the posted complete-case result; the registry’s enrollment figure is 100. The record does not provide enough detail to explain the difference between enrollment and the endpoint analysis counts, so it should not be attributed to any particular reason.

The registry identifies the study as randomized and double-masked, but detailed information about the randomization procedure, masking implementation, analysis model, covariate adjustment and analysis populations is not reported in the registry record. These omissions make it difficult to assess the full prespecified analysis strategy or to distinguish planned analyses from analyses selected after data collection.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 50 participants at risk for serious adverse events in each group and zero participants affected by a serious adverse event in each group. These counts describe the posted serious adverse-event figures. They do not establish that serious events were impossible or that the groups had identical safety profiles; they report only what is recorded for the stated at-risk groups.

For other adverse events, the record lists four affected participants in the Acoustic CR Neuromodulation group and three in the Tinnitus Masking group, with 50 at risk in each group. These are counts, not a detailed description of event types or severity. No serious adverse-event terms are listed. The registry record does not report death counts, so deaths should not be interpreted as zero.

Adverse-event counts are separate from the primary THQ outcome, which measures change in tinnitus-related functional impact. They do not by themselves establish a comparative safety conclusion. The registry record does not provide further detail about event definitions, timing, relatedness assessments or the method of collection.

16. What the Result Does, and Does Not, Mean

The posted primary result describes a small estimated difference in mean THQ change between CR Neuromodulation and tinnitus masking at 12 weeks. The estimate is 0.27 units, and its confidence interval includes zero and values in both directions. The unadjusted p-value is 0.914. Taken together, these statistics do not provide a precise distinction between the average outcomes in the two groups.

This is not the same as proving the two conditions are equivalent. Equivalence requires a prespecified margin defining differences small enough to be considered unimportant, along with an analysis designed to evaluate that margin. Neither an equivalence margin nor an equivalence design is reported in the registry record. A result that does not clearly distinguish groups can reflect a genuinely small difference, uncertainty due to variation, or both.

The result also should not be interpreted as showing that neither group changed. The endpoint means describe change within each group, while the primary comparison estimates the difference between those changes. The comparison is the relevant quantity for assessing relative group outcomes, and its uncertainty is substantial. Individual participants may have had changes unlike their group average; aggregate summaries do not show the full distribution of individual responses.

The scope is limited to the reported complete-case primary outcome at 12 weeks. The registry notes that a multiple-imputation analysis was conducted but does not report its result. The record does not report a clinically important difference threshold for the THQ, so the clinical importance of any particular difference cannot be inferred from statistical units alone. Nor does the outcome comparison test the proposed mechanism involving synchronized nerve firing.

Accordingly, the posted data support a cautious statistical reading: the estimated average contrast is near zero, but uncertainty remains about the size and direction of a difference. They do not establish clinical benefit, lack of benefit, equivalence, or a biological mechanism.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated effect should be read together with its uncertainty. The primary point estimate is close to zero, but the confidence interval spans differences favoring either group. Reporting only the estimate, or focusing only on the p-value, would conceal how much uncertainty remains about the comparison.

The design also highlights the importance of defining the comparator. Both groups received the same device, while the masking arm was not programmed according to the therapeutic algorithm. The contrast therefore concerns the two device conditions described in the registry, not device use compared with no device. Interpreting the result requires keeping that distinction in view.

The endpoint’s direction is another practical statistical detail. Change was calculated as baseline minus 12-week score, so positive values represent a reduction in symptoms. Stating the contrast direction and the endpoint’s scoring direction helps prevent a positive difference from being misread as worsening or improvement in the wrong group.

Finally, the registry presents a complete-case primary result while noting that multiple-imputed data were analyzed without reporting that result. This makes missing-data transparency important to judging robustness. The planning illustrations also demonstrate that calculations based on a small observed effect can require large hypothetical sample sizes, but such illustrations do not replace a justified design target. Together, these features show why estimates, intervals, analysis populations and design assumptions all matter in clinical-trial interpretation.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary comparison is based on complete-case data. Although the registry states that a multiple-imputation analysis was also performed, its result and methods are not reported. Missing outcome counts, reasons for missingness and sensitivity analyses are not reported, limiting assessment of whether the complete-case estimate could be affected by missing data.

The primary endpoint is measured at baseline and 12 weeks. The posted comparison does not establish whether outcomes persisted, changed or diverged after that time point. The registry summary mentions EEG measurement in a subset, but detailed numerical brainwave results are not reported in the registry record. The proposed neural mechanism therefore cannot be assessed from the primary THQ comparison.

The record identifies randomization and double masking but does not report operational details such as the allocation procedure, who was masked, or how masking was maintained. Detailed methods for the outcome analysis, including any adjustment for baseline measures or other covariates, are also not reported. The registry’s original sample-size justification and analysis plan are not reported, so it is not possible to judge whether the study was designed around a particular clinically important THQ difference.

The comparator used the same device without the therapeutic algorithm, rather than no device. The result therefore pertains to that specific contrast. The registry record does not report a clinically important difference threshold, and the confidence interval includes values on both sides of zero. These limitations mean the data do not support a precise conclusion about the size, direction or clinical importance of a difference between the device conditions.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of the CR Neuromodulation Treatment for Tinnitus — NCT01541969.
• Registry record last updated 2016-08-22; status last verified 2015-05.
• Results first posted 2015-06-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry record describes a completed randomized, double-masked, parallel-group study of acoustic CR neuromodulation for tinnitus, with enrollment of 100. The primary outcome was change in the global THQ score from baseline (visit 2) to 12 weeks (visit 6), calculated so positive values indicate reduced symptoms. The reported complete-case mean difference, Tinnitus Masking minus CR Neuromodulation, was 0.27 units, with a 95% confidence interval from -4.643 to 5.183 and an unadjusted p-value of 0.914.

The interval includes zero and differences in either direction, so the primary comparison is imprecise. The registry notes that multiple-imputed data were analyzed but reports complete-case results. Secondary numerical comparisons are posted for THI, TFI and WHOQOL-BREF; detailed results for all listed outcomes are not reported in the registry record. The original sample-size justification, detailed analysis plan and multiple-imputation results are also not reported.