Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere's Disease Outcomes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere's Disease Outcomes (NCT04218123), a randomized phase 2, phase 3 study. The primary outcome is Number of Vertigo Episodes.

2. Clinical Question

This is a statistical description of the registry results, not a treatment recommendation. The crossover design means participants were assigned to receive both treatment conditions in some order, but the record does not describe the sequence, periods, or analysis that accounts for within-participant comparisons. Those details matter when interpreting the precision of the treatment contrast.

3. Trial Design

The registry describes a randomized, quadruple-masked, crossover trial at Phase 2 and Phase 3. The brief summary calls it a pilot trial and describes a randomized, placebo-controlled, double-blind crossover study. The record reports 40 participants enrolled and lists venlafaxine and placebo oral tablet as the interventions. It is marked completed. The recorded start date is 2020-02-05, and the primary completion date is 2023-09-13.

A crossover design compares treatment conditions within participants, rather than assigning each participant permanently to only one condition. That general feature can make within-person information important to the analysis. The registry record does not report the treatment sequence, duration of each treatment period, any washout interval, or whether the posted summaries represent a particular period or a combined measure. It also does not explain how the statistical analysis handled the crossover structure.

The record lists 40 participants in each of the venlafaxine, placebo, and baseline outcome summaries. Those entries should not be added together to infer a total number of distinct participants: the baseline entry is not a separate randomized arm, and the trial is described as crossover. The registry record does not report the number of participants who completed each treatment period, the number included in each analysis, or a flow of participants through the trial.

The sponsor was the Medical University of South Carolina. The registered condition was Meniere Disease. Although the registry classifies the study as both Phase 2 and Phase 3, the record does not explain that phase designation or describe a separate phase-specific objective. Detailed protocol information, including dose, treatment schedule, allocation procedures, and the original statistical plan, is 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

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 Number of Vertigo Episodes, measured over 6 months.

The primary endpoint is the number of vertigo episodes, measured as a mean number of episodes over 6 months. The registry description says patients would keep a diary throughout the study period and beyond. It does not define the exact counting rules, explain how diary entries were summarized, or state how incomplete diaries were handled.

Counting episodes is a direct way to represent the frequency of the symptom targeted by the trial question. A mean provides a summary of the average count in a group or treatment condition, while the standard deviation describes how spread out individual counts are around that average. These are general statistical interpretations; the registry does not report additional endpoint validation or the expected distribution of episode counts.

The posted mean was 5.41 episodes in the venlafaxine arm and 5.03 in the placebo arm, with standard deviations of 4.44 and 4.57. A baseline score is also listed as a mean of 13.78 with a standard deviation of 10.05. The registry record does not make clear how the baseline measurement relates to the treatment-period endpoint, so it should not be treated as a treatment comparison.

The endpoint description does not specify a minimum meaningful difference or a threshold for clinical importance. The registry record also does not report whether the primary analysis used raw counts, a transformed measure, or a model designed for count outcomes. The posted mean comparison therefore describes the reported summaries, but cannot by itself answer questions about the analysis model or clinical importance.

7. Results Posted in the Registry

• Venlafaxine Arm: mean 5.41 versus 5.03 on control; difference 0.38 (95% CI -1.59 to 2.35), standardized effect d = 0.08; z-test p = 0.706.
• Baseline Score: mean 13.78 versus 5.03 on control; difference 8.75 (95% CI 5.33 to 12.17), standardized effect d = 1.12; z-test p = <0.001.

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.

Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI)

• 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:
  • Venlafaxine Arm: mean 46.81 versus 46.31 on control; difference 0.50 (95% CI -6.49 to 7.49), standardized effect d = 0.03; z-test p = 0.889.
  • Baseline Score: mean 50.68 versus 46.31 on control; difference 4.37 (95% CI -2.23 to 10.97), standardized effect d = 0.29; z-test p = 0.194.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Venlafaxine Arm and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Baseline Score and the control. The interval gives the range of effects that remain compatible with the data.

Change in Score on Penn State Worry Questionnaire (PSWQ)

• 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:
  • Venlafaxine Arm: mean 44.35 versus 45.63 on control; difference -1.28 (95% CI -7.38 to 4.82), standardized effect d = -0.09; z-test p = 0.681.
  • Baseline Score: mean 47.16 versus 45.63 on control; difference 1.53 (95% CI -4.52 to 7.58), standardized effect d = 0.11; z-test p = 0.620.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Venlafaxine Arm and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Baseline Score and the control. The interval gives the range of effects that remain compatible with the data.

Change in Score on Patient Health Questionnaire (PHQ9)

• 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:
  • Venlafaxine Arm: mean 5.49 versus 7.17 on control; difference -1.68 (95% CI -4.09 to 0.73), standardized effect d = -0.31; z-test p = 0.172.
  • Baseline Score: mean 7.43 versus 7.17 on control; difference 0.26 (95% CI -2.16 to 2.68), standardized effect d = 0.05; z-test p = 0.833.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Venlafaxine Arm and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Baseline Score and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts seven secondary outcomes covering quality of life, Meniere's disease symptoms, worry, depressive symptoms, cognitive failures, vertigo-related symptoms, and dizziness-related handicap. The posted outcomes include continuous score summaries and comparisons. Across the secondary results with sponsor-reported analyses, the registry reports ANOVA p-values of =0.538 for the Meniere's Disease Patient-Oriented Symptom Index, =0.686 for the Penn State Worry Questionnaire, and =0.167 for the Patient Health Questionnaire.

The broad pattern does not give a clear additional signal that changes the reading of the primary comparison. These are distinct measures, and their results should be interpreted in their own contexts rather than treated as interchangeable evidence about vertigo episode frequency. The registry record does not report a prespecified hierarchy linking the secondary outcomes to the primary endpoint, or clinical-importance thresholds for these scores.

Unadjusted secondary results carry less weight when many outcomes are tested. General statistical explanation: as the number of statistical tests increases, the chance of at least one apparently unusual result can increase even if there is no underlying effect. Methods such as a prespecified hierarchy or multiplicity adjustment can address this issue, but a multiplicity strategy is not reported in the registry record. It is therefore prudent to treat secondary comparisons as exploratory rather than as independent confirmation of the primary result.

The registry lists nine outcome measures overall and seven posted secondary outcomes. It does not explain the status or results of every measure in the record. No conclusions should be inferred about unposted outcomes from the results that are available.

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

• Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey
• Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI)
• Change in Score on Penn State Worry Questionnaire (PSWQ)
• Change in Score on Patient Health Questionnaire (PHQ9)
• Change in Score on Cognitive Failure Questionnaire (CFQ)
• Change in Score on Neuropsychological Vertigo Inventory (NVI)
• Change in Score on Dizziness Handicap Inventory (DHI)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

For a continuous outcome, a mean difference expresses the distance between two group means in the outcome's original units. Here, the primary outcome is reported as a mean number of vertigo episodes. The recalculated mean difference is 0.38, comparing venlafaxine with placebo. Its sign reflects the order of the comparison used in the recalculation; it does not by itself describe clinical importance. The standard deviations, 4.44 and 4.57, describe variability among the posted arm summaries, not uncertainty in the estimated treatment difference.

General statistical explanation: a standard error describes how much an estimate would tend to vary across repeated samples under a statistical model. It is distinct from a standard deviation, which describes variation in observations. The registry includes arm-level standard deviations and also an interval for the recalculated comparison. It does not report the sponsor's estimated treatment difference, its standard error, or an interval for that analysis.

How should the interval be read?

General statistical explanation: an interval estimate shows a range of values compatible with observed data under the assumptions used to calculate it. A narrow interval indicates greater precision than a wide interval, all else being equal. The recalculated primary interval extends from -1.595 to 2.355. Because it includes zero and values on either side, it is compatible with a range of possible directions for the mean difference. The registry record does not state the interval's confidence level, and it should not be assigned one without that information.

The recalculation is explicitly unadjusted and uses posted summary statistics. It does not reproduce a crossover analysis that accounts for the relationship between measurements from the same participant. General statistical explanation: in a crossover study, repeated treatment observations within a participant may be correlated. Ignoring that correlation can affect the estimated uncertainty. The registry record does not report enough detail to determine how the sponsor modeled within-participant data, sequence, or period effects.

What does ANOVA contribute?

The registry reports ANOVA analyses, including a comparison of venlafaxine and placebo and comparisons involving baseline. ANOVA is a general method for assessing whether group means differ, under a specified model. A significant overall test across several groups indicates that not all modeled means are the same; it does not on its own identify which comparison is responsible. Pairwise comparisons address particular group pairs, but their interpretation depends on how the analysis and any multiplicity adjustment were specified.

The sponsor's venlafaxine-versus-placebo ANOVA result is p > 0.05. The registry labels the reported analyses as equivalence analyses, but does not provide an equivalence margin, test statistic, estimate, or confidence interval. General statistical explanation: an equivalence analysis is not simply a test that fails to find a difference. It needs a prespecified range of differences considered acceptably small and evidence that the uncertainty is contained within that range. Without the margin and relevant estimates, the label alone cannot establish equivalence.

Why can over-dispersion matter for episode counts?

General statistical explanation: counts can have a distribution that differs from the assumptions of a simple normal model. Over-dispersion refers to variability greater than a chosen count model expects; if not accounted for, uncertainty estimates can be too small or otherwise poorly calibrated. The registry reports means and standard deviations for the episode count but does not report a count-model assessment, an over-dispersion check, or the model used for the sponsor's primary analysis. It is therefore not possible to say whether over-dispersion was assessed or how it affected the reported result.

The sponsor's reported analysis takes precedence over the summary-statistic recalculation because the registry record flags a discrepancy. The recalculation is a simple, unadjusted contrast from the posted means and dispersions, not an independent reanalysis of participant-level data. The record does not report participant-level data, protocol analysis details, missing-data methods, or sensitivity analyses. These omissions limit how fully the posted result can be independently evaluated.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 0.38 episodes, with a reported interval from -1.595 to 2.355 and p = 0.706. The interval ranges across zero, so the recalculation does not precisely determine the direction of the mean difference. It is also wide enough to include differences on either side of zero; the estimate should not be read as proof that the treatment conditions have the same mean.

General statistical explanation: an interval conveys uncertainty around an estimate, while a p-value summarizes compatibility with a null hypothesis under a model. Neither measure gives the probability that a particular effect is true. Precision depends on the amount and variability of information and on the analysis model. The reported standard deviations, 4.44 for venlafaxine and 4.57 for placebo, show appreciable variation in the episode counts relative to the mean summaries.

The registry does not state the confidence level associated with the recalculated interval. The reported interval should therefore be read as posted, without assigning it a level not documented in the record. More importantly, the crossover design calls for an analysis that can use the within-participant structure. The summary-statistic recalculation does not document such an adjustment, and participant-level data are not reported.

The sponsor-reported treatment comparison is an ANOVA with p > 0.05, but the registry does not report its effect estimate or interval. That result alone cannot show how large or small the sponsor's estimated difference may be. The record also does not report a clinically meaningful difference threshold. Together, these omissions constrain conclusions about both statistical precision and practical importance.

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 examples based on the observed effect, not a report of the trial's original design assumptions. For these continuous outcomes, the figures are participants per arm, rather than total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each illustration targets the stated fraction of the observed effect. The original sample-size justification and assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm in a hypothetical study intended to have an 80% chance of detecting the specified effect under the stated planning assumptions, if that effect were present. The 90% power column gives the corresponding per-arm planning number for a 90% chance. These are design calculations, not observed results. This is not observed power.

Rows describe planning for 100%, 75%, and 50% of the observed effect. Smaller effects require more participants to detect under the same assumptions, so the planning numbers increase as the target effect becomes a smaller fraction of the observed effect. This relationship is general: when a study seeks to distinguish a smaller difference from random variation, more information is usually needed.

These illustrations should not be treated as a recommendation for a future trial or as evidence about the original trial's adequacy. They use the observed effect as an input, and observed effects from small studies can be imprecise. The registry record does not report an original target effect, a planned power, or a sample-size calculation. The crossover design also raises design-specific considerations that a simple equal-allocation, two-arm planning illustration may not capture.

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 = 0.380; pooled standard deviation σ = 4.505.
2. n = 2 × (1.96 + 0.842)² × 4.505² / 0.380² = 2,206.7, rounded up to 2,207 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 <- 0.38                      # observed difference in means
sigma <- 4.50546889901595                     # 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(4218123)
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 = 2,207 (80% power), 2,955 (90% power)
 75% of observed effect: n per arm = 3,924 (80% power), 5,252 (90% power)
 50% of observed effect: n per arm = 8,827 (80% power), 11,817 (90% power)
power.t.test: 2207.7 
Simulated power at n = 2,207 per arm: 0.798 (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. Analyses Reported by the Sponsor

The sponsor's reported primary comparison is an ANOVA of the venlafaxine and placebo groups, with p > 0.05. The registry does not give the sponsor's estimated difference, interval, or detailed model specification for this comparison. It also reports ANOVA comparisons involving baseline, including an overall p < 0.001 and pairwise results against baseline with p < 0.05. Baseline is not a randomized treatment condition, so those comparisons do not replace the treatment-versus-placebo contrast.

The unadjusted recalculation from posted summary statistics estimates a mean difference of 0.38 episodes, with a reported interval from -1.595 to 2.355 and p = 0.706. The record flags a discrepancy between the recalculation and the sponsor's analysis. The sponsor's own analysis takes precedence; the recalculation is a transparent descriptive check from group summaries, not a correction to the sponsor's analysis or a crossover-specific reanalysis.

The registry labels the analyses as equivalence analyses, but it does not report an equivalence margin or enough detail to determine whether equivalence was established. A p-value above 0.05 is not by itself evidence of equivalence. Without the sponsor's estimate, interval, analysis details, and margin, the posted results do not permit a full assessment of the sponsor's equivalence claim.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports a primary outcome and multiple secondary outcomes, as well as several ANOVA comparisons. It does not report whether the statistical plan used a hierarchy among endpoints, adjusted for multiple comparisons, or designated secondary analyses as exploratory. When many hypotheses are tested, the chance of at least one nominally notable result can rise. That general concern makes unadjusted secondary findings less conclusive than a single prespecified primary analysis.

The record labels several ANOVA results as equivalence analyses but does not report an equivalence margin, the full test procedure, or confidence intervals for the sponsor's analyses. It also does not report an interim analysis plan or whether any interim analyses were conducted. The original statistical analysis plan is not reported in the registry record.

Missing-data handling is not reported. The record does not state whether all enrolled participants contributed to every endpoint, how incomplete symptom diaries or questionnaire responses were treated, or whether any imputation or sensitivity analyses were used. It also does not provide an analysis population definition, such as whether analyses included all randomized participants or only those who completed treatment conditions.

These gaps matter particularly for a crossover design, where the number of observations available from each participant and treatment condition can affect the analysis. The registry does not report treatment sequence, period effects, carryover considerations, or how within-person correlation was handled. Without those details, it is difficult to evaluate the correspondence between the sponsor's reported ANOVA and the design or to assess whether missing observations could have altered the treatment comparison.

The absence of these details does not demonstrate that the analyses were inappropriate; it limits what can be verified from the registry record. The reported estimates and tests should be read with that constraint, especially for claims about equivalence, secondary endpoints, and the completeness of the analysis population.

16. 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 non-serious adverse event terms

The serious adverse event summaries list 40 participants at risk in each arm and zero serious adverse events affecting participants in both the venlafaxine and placebo arms. The record also lists zero deaths in each arm. No serious adverse event terms are listed.

For other adverse events, the registry lists 6 affected in the venlafaxine arm and 3 in the placebo arm, with 40 at risk in each. These are the figures posted in the record; the registry does not provide event descriptions or further detail about severity, timing, or how events were attributed to treatment.

Zero reported serious adverse events in these summaries does not establish that no serious events could occur, and the other-event counts alone do not establish a causal difference between treatment conditions. The record does not report how safety comparisons were analyzed or whether the crossover periods were considered separately. These figures are descriptive summaries, not a stand-alone assessment of safety.

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

The posted primary summaries describe mean vertigo episode counts of 5.41 with venlafaxine and 5.03 with placebo over 6 months. The sponsor-reported treatment comparison has p > 0.05. The unadjusted recalculation estimates a mean difference of 0.38, with a reported interval from -1.595 to 2.355 and p = 0.706. These results do not establish that the treatments are equivalent, nor do they establish a treatment effect of a particular size.

A nonsignificant test is not evidence that an effect is absent. It indicates that the analysis did not provide strong evidence against its null hypothesis under its assumptions. Likewise, a point estimate near zero is not proof that the true difference is zero. The interval illustrates uncertainty, but the record does not provide the sponsor's interval or a stated threshold for clinical importance.

The registry labels the sponsor analyses as equivalence tests, but does not report the margin required to interpret equivalence. Therefore, the equivalence label cannot be independently evaluated from the posted information. The record also lacks detail about the crossover analysis, missing data, and the analyzed population, which limits assessment of how the design was incorporated.

The results describe a small pilot trial with 40 participants enrolled. They are not a basis for medical advice, and they should not be generalized beyond the population and outcomes represented in the registry. The posted secondary outcomes add context but do not resolve the limitations of the primary analysis. No claim about efficacy or lack of efficacy follows from the p-value alone.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison needs more than a point estimate or a p-value. The primary summaries give a mean difference of 0.38 episodes, while the recalculated interval spans values on either side of zero. That combination makes uncertainty visible: the estimate alone is not enough to determine whether a meaningful difference exists.

The crossover design also highlights the importance of matching analysis to design. Participants in crossover studies contribute observations under more than one treatment condition, so within-participant relationships may be relevant. The registry identifies the design but does not report how those relationships, treatment sequence, or periods entered the sponsor's analysis. This is a reminder that a test label such as ANOVA does not fully describe a model.

The record's discrepancy flag is another important statistical feature. A summary-statistic recalculation can provide a simple check, but it does not replace the sponsor's own analysis or resolve the difference between analyses. Because the sponsor's analysis takes precedence, interpretation should distinguish its reported p-value from the unadjusted recalculation and avoid treating them as interchangeable.

Finally, the outcome set includes multiple secondary measures, while the registry does not report a multiplicity plan or equivalence margin. These omissions constrain claims based on secondary tests and on equivalence labels. Transparent reporting of estimates, uncertainty, analysis populations, and prespecified methods is essential for readers to judge how much the results support.

19. 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 registry record gives limited detail about the crossover implementation. Treatment sequence, period duration, washout arrangements, and the handling of period or carryover effects are not reported. The sponsor's statistical model and its treatment of within-participant correlation are also not described. These are design-specific details relevant to interpreting the primary comparison.

The primary outcome description says participants kept diaries throughout the study and beyond, but the registry does not define episode-counting rules or explain how incomplete diary data were handled. Missing-data procedures, analysis populations, and participant completion by treatment condition are not reported. The record lists 40 participants for each arm summary, but does not provide a participant flow or clarify the analysis set for every outcome.

The sponsor's results are reported as ANOVA p-values without effect estimates or intervals for the primary treatment comparison. Although the analyses are labeled as equivalence analyses, the equivalence margin is not reported. The registry also does not report the original sample-size justification, interim-analysis plan, or multiplicity strategy. These gaps limit independent assessment of the evidence and of the equivalence interpretation.

The unadjusted recalculation is based on posted group means and standard deviations, not participant-level data. The record flags a discrepancy, so the sponsor's own analysis takes precedence. The recalculation cannot establish that the crossover structure was properly represented. Finally, the trial is described as a pilot, and the record does not report thresholds for clinically important differences on the primary or secondary outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere's Disease Outcomes — NCT04218123.
• Registry record last updated 2024-07-23; status last verified 2024-06.
• Results first posted 2024-06-24.
• 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.

23. Record Summary

The registry record describes a completed randomized, quadruple-masked crossover study of venlafaxine and placebo for Meniere's disease, with 40 participants enrolled. The primary outcome was the number of vertigo episodes over 6 months, recorded by diary. Posted means were 5.41 in the venlafaxine arm and 5.03 in the placebo arm.

The sponsor reported an ANOVA treatment comparison with p > 0.05. An unadjusted recalculation from the posted summaries estimates a mean difference of 0.38, with a reported interval from -1.595 to 2.355 and p = 0.706. Because the registry flags a discrepancy, the sponsor's analysis takes precedence. The record does not report an equivalence margin, detailed crossover analysis, missing-data methods, or the original sample-size rationale.

Seven secondary outcomes are posted. Safety summaries list zero serious adverse events and zero deaths in both arms. These registry results are limited by incomplete reporting of analysis details and do not by themselves establish equivalence or clinical importance.