Tinnitus Retraining Therapy Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tinnitus Retraining Therapy Trial (NCT01177137), a randomized phase 3 study. The primary outcome is Change in Tinnitus Questionnaire (TQ) From Baseline to 3, 6, 12, and 18 Months.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-masked, parallel-group trial with an enrollment of 151 participants. The registry record lists subjective tinnitus as the condition and identifies Johns Hopkins Bloomberg School of Public Health as the sponsor. The study started in 2011-07, reached primary completion in 2017-02, and has a completed status.

Participants were assigned among three arms. The TRT arm received a conventional sound generator and directive counseling. The Partial TRT arm received a placebo sound generator and directive counseling. The standard-of-care arm received care described as typically delivered in US military medical centers. The registry identifies the study as double-masked but does not report which people, if any, were masked to each treatment assignment or how masking was maintained.

The primary outcome was a continuous measure: mean change in TQ score from baseline at 3, 6, 12, and 18 months. Secondary outcomes included changes in the Tinnitus Functional Index, Tinnitus Handicap Inventory, Tinnitus Retraining Therapy Interview visual analogue scales, and Tinnitus Questionnaire subscales. The registry lists 20 outcome measures and 38 analyses.

Although the trial is marked completed, completion status alone does not establish what the results were or whether every planned analysis was reported. Primary-outcome estimates, uncertainty intervals, and between-arm comparisons are not reported in the registry record. Details about the randomization procedure, allocation concealment, and the identities of masked groups are also not reported in 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat, including data from all participants with at least one follow-up visit

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 Change in Tinnitus Questionnaire (TQ) From Baseline to 3, 6, 12, and 18 Months, measured over Baseline to 3, 6, 12, and 18 months follow-up.

The primary endpoint was mean change in the Tinnitus Questionnaire (TQ) from baseline to follow-up at 3, 6, 12, and 18 months. The TQ is a tinnitus-specific health-related quality-of-life instrument containing 52 statements, each marked true, partly true, or not true. Its score ranges from 0 to 102; higher scores indicate a greater impact of tinnitus on quality of life.

The TQ covers several dimensions, including emotional distress, intrusiveness, auditory perceptual difficulties, sleep disturbance, and somatic complaints. A change score is intended to describe how a participant’s measured TQ score differs from baseline at a follow-up visit. Reporting changes at several time points can describe the course of scores during follow-up, but does not by itself establish why a score changed or whether a difference between groups is statistically persuasive.

The registry specifies a mean and standard deviation for this continuous outcome and defines the primary-outcome population as intention to treat, including participants with at least one follow-up visit. The primary-outcome results, including group means, change estimates, and uncertainty intervals, are not reported in the registry record. Consequently, the direction and precision of the observed TQ changes cannot be assessed from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous score, and the registry describes it using a mean and standard deviation. A mean summarizes the average score or change within a group. A standard deviation describes how spread out individual measurements are around that average. These quantities answer different questions: a mean describes the group’s central value, while a standard deviation describes variation among participants.

For a randomized comparison, the central statistical question is generally the difference in outcomes between assigned groups, not merely whether scores changed within each group. Within-group changes can reflect many influences, including time and events shared by participants; a between-group estimate is needed to quantify the contrast associated with assignment under the trial design. The primary-outcome estimates and the details of the comparison model are not reported in the registry record, so the specific analysis cannot be reconstructed.

A confidence interval is a statistical range expressing uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not show the range of individual participants’ scores. Confidence intervals for the primary outcome are not reported in the registry record. A p-value, when reported, measures how incompatible the observed data are with a specified null model; it does not quantify the size or clinical importance of an effect. Primary-outcome p-values are not reported in the registry record.

The scheduled assessments were baseline and follow-up at 3, 6, 12, and 18 months. Repeated measurements can be analyzed in different ways. For example, an analysis might compare change at each visit separately or model measurements over time jointly. These approaches make different assumptions and can handle incomplete observations differently. The registry does not report the statistical model, the treatment of within-participant correlation, or whether a single time point or an overall pattern was the main inferential focus.

The registry specifies an intention-to-treat population including participants with at least one follow-up visit. In general, intention-to-treat analysis aims to preserve the randomized assignment when comparing groups. The recorded population definition does not, by itself, explain how participants without follow-up data were treated, whether all randomized participants were included in every analysis, or how deviations from assigned treatment were handled. Those details are not reported in the registry record.

Missing observations matter because the availability of follow-up scores can affect both the precision and the interpretation of an estimate. If participants with missing measurements differ from those observed, an analysis restricted to available cases can be vulnerable to bias. Statistical methods can make assumptions about missingness, but the assumptions and any sensitivity analyses for missing TQ data are not reported in the registry record. The number of participants measured at each visit is also not reported in the registry record.

The record lists 20 outcome measures and 38 analyses. When a study evaluates multiple outcomes, time points, or comparisons, the chance of obtaining at least one apparently noteworthy result can increase if all analyses are treated as independent opportunities for a finding. Methods such as prespecifying a primary contrast or adjusting for multiple testing can address particular multiplicity concerns. The registry information does not report whether any multiplicity adjustment was planned or applied, nor does it provide a full statistical analysis plan.

The record also describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration concerns hypothetical planning under stated assumptions; it is not observed power and does not report the probability that this completed trial detected a true effect. The particular effect fractions and participant-count values are not reported in the registry record details available for this description. The trial’s original sample-size justification is not reported in the registry record.

In general, over-dispersion means that variability in observed data is greater than a model assumes. It can make standard errors and confidence intervals based on an overly restrictive model unreliable. The primary endpoint is continuous and summarized by a mean and standard deviation; the registry does not identify over-dispersion as an issue or report a model check. No claim about over-dispersion in this trial is warranted.

Randomization supports comparisons by assignment when the allocation process and analysis are appropriately implemented, but it does not eliminate uncertainty or guarantee complete follow-up. Information about sequence generation, allocation concealment, interim analyses, model diagnostics, and the statistical analysis plan is not reported in the registry record. Without those details and the outcome estimates, readers cannot audit the analysis choices or evaluate the robustness of the reported primary result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures and 38 analyses. The primary outcome itself is measured at 3, 6, 12, and 18 months, while the listed secondary outcomes include other instruments and Tinnitus Questionnaire subscales. Multiple outcomes, time points, and comparisons raise a multiplicity question: testing many contrasts can increase the chance that at least one result appears notable by chance. The registry does not report whether a multiplicity strategy was prespecified, whether adjustment was used, or which comparisons were considered confirmatory.

The primary-outcome population is described as intention to treat and includes data from all participants with at least one follow-up visit. The registry record does not report the number contributing data to each visit, the number excluded from particular analyses, or the method used to handle missing observations. It also does not report whether sensitivity analyses examined how missing data could affect the findings.

These omissions limit assessment of both multiplicity and missing-data assumptions. They do not establish that the analysis was inappropriate; they mean that the relevant choices and their consequences cannot be evaluated from the registry record. The original analysis plan, any interim analyses, and any departures from planned methods are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cancer (3.9%), surgery (2.0%).

For serious adverse events, the registry reports 0 affected participants among 51 at risk in the TRT arm, 3 among 51 at risk in the Partial TRT arm, and 0 among 49 at risk in the standard-of-care arm. Deaths are reported as 0 in each of the three arms. These are the recorded counts; they do not describe the primary TQ outcome.

For other adverse events, the reported affected counts are 10 among 51 at risk in the TRT arm, 12 among 51 at risk in the Partial TRT arm, and 9 among 49 at risk in the standard-of-care arm. The registry also lists Cancer at 3.9% and Surgery at 2.0% among the top serious adverse-event terms. It does not report how those terms were distributed across arms in the information.

Adverse-event counts do not by themselves establish whether an event was caused by treatment, how severe it was beyond its classification, or how long it lasted. The registry record does not report the attribution criteria or additional event-level details needed to answer those questions. The figures should therefore be read as reported safety counts, not as proof of causation or as a complete account of treatment benefit and harm.

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

The record identifies a randomized comparison of TRT, Partial TRT, and standard care, with change in TQ score as the primary outcome. It also gives the scale’s direction and follow-up schedule, describes the treatment components, and reports selected adverse-event counts. Those details clarify what the trial set out to compare and what kinds of observations were collected.

The primary-outcome results are not reported in the registry record. No direction, magnitude, or precision of the TQ comparison can therefore be stated. In particular, the record information does not show whether mean scores changed in any arm, whether one arm differed from another, or whether any between-arm estimate was compatible with a range of effects. The absence of reported estimates is not evidence that the arms were equivalent or that no change occurred.

Even if outcome estimates were available, their interpretation would require attention to the size and uncertainty of the differences, the participants represented in each analysis, and the treatment of missing measurements. Statistical evidence and clinical importance are also distinct: a small estimate can be precise, and a larger estimate can be uncertain. The registry entries do not permit those judgments for the primary endpoint.

The safety counts are similarly limited. They record affected participants and deaths by arm, but do not establish that an event was caused by an assigned treatment. They also do not substitute for a complete account of all benefits and harms. No medical advice or treatment recommendation follows from these registry entries.

The appropriate conclusion is narrow: this completed phase 3 trial was designed to compare three approaches and assessed a tinnitus-specific quality-of-life measure over follow-up. The record described does not report the primary results needed to characterize the comparative outcome. A completed status and a stated objective should not be mistaken for evidence of a particular result.

13. Why This Trial Matters Statistically

Statistically, the trial is notable for asking a comparative question across three treatment approaches while tracking a continuous, patient-reported measure over multiple follow-up times. The primary endpoint captures tinnitus-related quality of life through a 52-statement instrument, with higher scores indicating greater impact. That definition makes the direction of the scale interpretable, but interpretation of treatment contrasts still depends on reported estimates and their uncertainty.

The intervention structure distinguishes TRT, which combines a conventional sound generator with directive counseling, from Partial TRT, which combines a placebo sound generator with directive counseling. Standard care supplies a third comparison. This design makes it important to identify which contrast an estimate represents; an overall statement about “treatment” would obscure the different components and comparators.

Multiple outcomes and repeated assessments create analytical choices about which comparisons are primary, how measurements over time are modeled, and how multiplicity is addressed. The registry lists 20 outcome measures and 38 analyses, but does not report the statistical plan or multiplicity handling. Missing follow-up data are another important consideration because the primary population is defined to include participants with at least one follow-up visit, while visit-specific counts and missing-data methods are not reported.

The trial also illustrates why design information and results must be read separately. Randomized, double-masked, parallel-group labels describe important aspects of the design, but do not supply the estimates needed to assess the primary question. The primary results are not reported in the registry record. Consequently, this record can inform readers about the planned comparison and outcome definition, but not the comparative effect or its precision.

14. 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 central limitation for interpreting this trial record is that primary-outcome estimates are not reported in the registry record. Group-level changes, between-arm contrasts, confidence intervals, and p-values are not available in the information described. The comparative result, its direction, and its precision therefore cannot be assessed.

The record identifies the primary outcome as mean change at several follow-up times, but does not specify the model used to analyze repeated measurements or how the multiple time points were incorporated into inference. It lists 20 outcome measures and 38 analyses without reporting whether multiplicity was addressed. The full statistical analysis plan and the trial’s original sample-size justification are not reported in the registry record.

Although the primary population is described as intention to treat with at least one follow-up visit, the record does not report visit-specific participant counts, the handling of missing TQ measurements, or sensitivity analyses. It also does not report the randomization procedure, allocation concealment, which parties were masked, or how masking was maintained. These missing details restrict assessment of implementation and analysis, but do not establish that any particular procedure was inadequate.

Safety reporting is limited to the counts described and selected serious adverse-event terms. The record does not provide the event-level detail or attribution information needed to assess whether events were related to assigned interventions. These limitations are specific to the information reported in the registry record and should not be confused with evidence that the trial itself lacked additional analyses or documentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Tinnitus Retraining Therapy Trial — NCT01177137.
• Registry record last updated 2018-11-21; status last verified 2018-10.
• Results first posted 2018-11-21.
• 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.

18. Record Summary

NCT01177137, titled Tinnitus Retraining Therapy Trial, is a completed phase 3 randomized, double-masked, parallel-group trial sponsored by Johns Hopkins Bloomberg School of Public Health. Enrollment was 151. The recorded start was 2011-07 and primary completion was 2017-02. Subjective tinnitus is listed as the condition.

The three arms were TRT with a conventional sound generator and directive counseling, Partial TRT with a placebo sound generator and directive counseling, and standard of care. The primary outcome was mean change in TQ score from baseline to 3, 6, 12, and 18 months among participants with at least one follow-up visit.

The registry lists secondary outcomes, 20 outcome measures, and 38 analyses. It reports selected adverse-event counts and zero deaths in each arm. The primary-outcome results and detailed statistical analysis plan are not reported in the registry record.