The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD) (NCT04279522), a randomized na study. The primary outcome is Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score.

2. Clinical Question

The central statistical question is about the difference in average change between the randomized groups, not simply whether either group’s score changed from baseline. The posted results report mean changes for each group and an active-versus-sham mean difference. A negative change represents a lower score at follow-up than at baseline; because higher HDRS-17 scores indicate more severe symptoms, a decline is directionally consistent with improvement in the measured score. This interpretation concerns the scale outcome and does not by itself establish a causal or clinical conclusion.

The study also recorded response, remission, and change on the MADRS total score as secondary outcomes. These provide additional views of symptoms, but the primary question remains the between-group comparison on HDRS17 total score at the stated 8-week time point. The registry record does not report a threshold defining response or remission, nor does it describe how the mITT population was determined.

3. Trial Design

The MOOD Study is listed as a randomized, parallel-group trial with active stimulation and sham stimulation. The registry describes the study as prospective, multi-center, and sham-controlled. Its design fields identify quadruple masking, while the study summary calls the study double-blind. The record does not explain the difference between those masking descriptions or identify which study roles were masked.

The registry lists an enrollment of 124 and a planned 1:1 randomization to Relivion®DP active stimulation or sham control. Enrollment is a trial-level figure; the posted primary endpoint results are reported for an mITT population, with group sizes of 47 for active stimulation and 50 for sham stimulation. The registry record does not explain how those endpoint group sizes relate to the enrollment figure, such as whether the difference reflects exclusions, missing outcome data, or another analysis-population rule.

The described study sequence included screening, eligibility evaluation, and randomization at baseline on Day 0; a daily active or sham treatment period from baseline to the end of 8 weeks; and an open-label active-treatment period for an additional 8 weeks. The primary outcome timeframe is 8 weeks from treatment initiation, so the reported primary comparison corresponds to the randomized active-versus-sham stage rather than the later open-label period.

The registry lists the study as completed, with a start date of 2021-08-31 and a primary completion date of 2024-06-07. The listed phase is NA. The sponsor is Neurolief Ltd. Details such as the original sample-size justification, protocol amendments, site count, randomization implementation, and trial-specific analysis plan are not reported in the registry record. The posted results therefore permit a description of the reported group summaries and comparisons, but not a full audit of how the trial was designed and conducted.

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.

Period 1: Double Blind Phase

Reasons for not completing this period:

Period 2: Open Label Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: mITT

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 Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score, measured over 8 weeks from treatment initiation.

The primary endpoint is mean change in depressive symptoms, measured by HDRS17 total score from baseline to week 8 after treatment initiation. HDRS-17 is a clinician-administered questionnaire designed to assess depressive symptom severity. Its total score ranges from 0 to 52, and higher scores indicate more severe depression.

Change from baseline expresses how the measured score shifted during the treatment period. Comparing the mean change between randomized groups is useful because the sham group provides a concurrent reference for changes that may occur over time regardless of active stimulation. The resulting mean difference summarizes the average separation between the group changes in the posted analysis. It is not the same as the change observed within either group alone.

The registry identifies the primary analysis population as mITT and reports mean change with standard error as the measure of dispersion. The posted group means are -8.62 for active stimulation and -6.01 for sham stimulation; the reported active-minus-sham mean difference is -2.61. Since higher HDRS-17 scores indicate more severe symptoms, the negative changes in both groups indicate lower average scores at follow-up than at baseline. The between-group estimate describes the additional separation in mean change, while its interval and p-value describe statistical uncertainty under the reported comparison.

The registry does not report a threshold for a clinically important difference on HDRS-17 or explain how the mITT population was defined. The statistical endpoint can therefore be interpreted as a comparison of average score changes, while the clinical importance of the estimate requires context not contained in the registry record.

7. Results Posted in the Registry

• Group 1 - Active Stimulation: mean -8.62 versus -6.01 on control; difference -2.61 (95% CI -4.93 to -0.29), standardized effect d = -0.45; z-test p = 0.027.

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.

Percentage of Responder Participants

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group 1 - Active Stimulation: 31.9% (15/47) versus 18.0% (9/50) on control; risk difference 13.9 percentage points (95% CI -3.1 to 31.0), risk ratio 1.77 (0.86–3.66); unadjusted two-proportion z-test p = 0.112.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 1 - Active Stimulation and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects Achieving Remission

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group 1 - Active Stimulation: 21.3% (10/47) versus 6.0% (3/50) on control; risk difference 15.3 percentage points (95% CI 1.9 to 28.7), risk ratio 3.55 (1.04–12.10); unadjusted two-proportion z-test p = 0.027.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Group 1 - Active Stimulation than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change in Depressive Symptoms, Measured by MADRS Total Score

• 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 errors.
• Result:
  • Group 1 - Active Stimulation: mean -10.18 versus -8.09 on control; difference -2.09 (95% CI -5.62 to 1.44), standardized effect d = -0.24; z-test p = 0.246.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 1 - Active Stimulation and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover participant response, remission, and mean change on MADRS total score. Taken together, their estimates point in the same broad direction as the primary comparison in the sense that the posted active-group results are more favorable on the reported symptom measures. However, the strength and precision of the comparisons vary: the remission interval is above zero, while the response and MADRS intervals include zero. That pattern is not a uniform set of equally precise findings.

These endpoints relate to the primary result by addressing other ways to describe depressive symptoms at the same 8-week timeframe. HDRS17 mean change is the primary endpoint; the secondary binary outcomes capture whether participants met response or remission criteria, while MADRS measures symptom change on another scale. Such outcomes can complement the primary measure, but their estimates do not replace it, and none alone establishes whether the observed differences are clinically important.

Unadjusted secondary results carry less weight because multiple outcomes create more opportunities to observe apparently noteworthy results by chance. General: when many hypotheses are tested, the chance of at least one small p-value can rise unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for interpreting the secondary outcomes. Their p-values should consequently be read as unadjusted evidence for their individual comparisons, not as confirmatory tests with an established family-wise error control.

The record lists three secondary outcome measures, while the registry outcome-measure count is seven. It does not explain the difference between these listings or provide reported analyses for the secondary outcomes. This incomplete analysis detail makes it difficult to know whether all intended secondary comparisons are represented in the posted results. The overall pattern is useful for context, but the primary endpoint remains the clearest basis for describing the randomized comparison, with secondary outcomes treated as supportive and more tentative evidence.

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

• Percentage of Responder Participants
• Percentage of Subjects Achieving Remission
• Mean Change in Depressive Symptoms, Measured by MADRS Total Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison is a difference in mean change between the active-stimulation and sham-stimulation groups. For each participant in the analysis, change refers to the difference between baseline HDRS17 total score and the week-8 score. The posted group mean changes are then compared. A mean difference close to zero would indicate similar average change in the groups; a difference away from zero indicates separation in their average changes. The sign depends on the order of subtraction, which the registry reports as active stimulation relative to sham.

What does the standard error describe?

The registry reports standard error for each group mean change. In general, a standard error describes the precision of an estimated mean: it reflects how much the estimate would tend to vary across comparable samples under the statistical assumptions. It is not a description of how much individual participants’ scores varied. A standard error is also not itself a range containing individual outcomes. The posted standard errors for the primary group means are 0.848 for active stimulation and 0.826 for sham stimulation, rounded to no more than three decimal places.

For the between-group estimate, the registry posts a mean difference of -2.61 and an interval from -4.929 to approximately -0.291. In general, an interval presents a range of values compatible with the data and analysis assumptions, while communicating uncertainty around the estimate. The registry does not identify the interval’s confidence level or provide the detailed method used to construct it. It is therefore appropriate to describe the reported range and whether it includes zero, but not to assign an undocumented confidence level or claim a particular interval procedure.

How should the p-value be read?

The primary unadjusted p-value is 0.027. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis as those observed would be, assuming the null model and analysis assumptions. It does not measure the probability that the null hypothesis is true, nor does it express the probability that the result will reproduce. The p-value is unadjusted, and the registry does not report whether the analysis applied a significance threshold or corrected for multiple testing. It should be read alongside the effect estimate and interval, not in isolation.

The randomized parallel-group design makes the active-versus-sham contrast the relevant comparison for the stated treatment period. A before-and-after change within the active group alone would not distinguish the effect of active stimulation from changes that may also occur under sham treatment or with time. The sham group supplies the concurrent comparison. Randomization can support a fair comparison in expectation, but the record’s brief description does not document allocation concealment, baseline balance, adjustment choices, or departures from the intended assignment.

What can the secondary estimates tell readers?

The response and remission outcomes are binary in the posted results: participants are counted according to whether they met the corresponding outcome. Their active-versus-sham comparisons are reported as risk differences. In general, a risk difference compares the proportions in the two groups by subtracting one group’s event proportion from the other’s. An interval that includes zero indicates that no difference is among the values compatible with that interval’s assumptions; an interval wholly on one side of zero indicates a directional difference in the reported comparison. The remission interval is above zero, whereas the response interval includes zero.

MADRS total score is a continuous measure, and the posted secondary comparison is a difference in mean change. Its estimate is -2.09, with an interval that includes zero. The meaning of that estimate is distinct from the HDRS17 comparison because it uses a different symptom measure. In general, different scales can provide related but non-identical information, and results from one scale should not be substituted for another.

For binary outcomes, the registry also posts relative measures, including risk ratios and odds ratios. Those measures compare outcomes on relative rather than absolute scales. They are not needed to understand the risk-difference estimate and should be read with their own intervals and assumptions. The registry record does not report adjusted analyses for the secondary endpoints, and the reported analyses list is empty.

Why does over-dispersion matter?

General: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than is present, it can understate uncertainty and make intervals too narrow or p-values too small. It is especially relevant in settings where outcome counts or clustered observations are modeled. The registry does not report an over-dispersion assessment or a count-model analysis for these outcomes, so this general issue should not be mistaken for a documented feature of the MOOD analysis.

Overall, the posted analyses allow readers to describe the observed group summaries and reported comparisons. They do not give a complete account of model specifications, missing-data procedures, multiplicity control, or sensitivity analyses. Those details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -2.61, with a reported interval from -4.929 to approximately -0.291. The interval lies on the negative side of zero, matching the direction of the estimate and indicating that the posted comparison is not centered on no difference. Its width also shows that the plausible values span more than a single precise value. The registry record does not state the interval’s confidence level or construction method, so the limits can be described as reported without assigning further technical details.

In general, a confidence interval expresses uncertainty in an estimated effect under the analysis assumptions. A narrower interval indicates greater precision than a wider interval on the same scale; an interval that crosses zero leaves both directions of difference compatible with the stated interval. The primary interval does not cross zero, whereas the MADRS interval does. The response interval also crosses zero, while the remission interval is above zero. These distinctions describe the posted estimates and do not on their own establish clinical importance.

The primary group standard errors are 0.848 for active stimulation and 0.826 for sham stimulation. Standard errors quantify precision of the estimated group means, not the range of participant-level responses. The active and sham endpoint groups are reported as 47 and 50 in the mITT population. The registry does not explain how missing observations or the analysis population were handled, which limits assessment of how those features may affect precision.

Interval estimates are more informative than p-values alone because they communicate the direction and range of the estimated difference. Even when an interval excludes zero, uncertainty remains about the exact size of the difference. The posted primary interval is consistent with a negative difference in mean change under its assumptions, but the registry record does not report a clinically important threshold for HDRS-17. Statistical precision and clinical relevance are related questions, not interchangeable ones.

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 planning figures are illustrations based on the observed effect, not the trial’s original design calculation. The registry’s planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The listed figures are participants per arm, not total participants, for these continuous and binary outcomes.

The 80% power column gives the planned number of participants per arm under the stated assumptions for an analysis with 80% power to detect the chosen effect. The 90% power column gives the corresponding number per arm for 90% power. In general, power is the probability of detecting an effect of the specified size under the assumed model if that effect is present. These are planning quantities, not observed power for the completed trial.

Each row represents planning for a different fraction of the observed effect. Planning for 75% of the observed effect gives a smaller target effect than planning for 100% of the observed effect; planning for 50% gives a smaller target still. Smaller effects are harder to distinguish from random variation, so the planning figures require more participants per arm. This pattern applies to the posted illustrations across the primary and secondary comparisons.

For the primary HDRS17 comparison, the planning figures for 100% of the observed effect are 79 participants per arm for 80% power and 105 participants per arm for 90% power. The corresponding figures for planning for 75% of the observed effect are 140 and 187; for 50% they are 313 and 419. The trial’s original sample-size assumptions and justification are not reported in the registry record. The planning illustration should therefore be used to understand how assumed effect size and desired power relate to sample size, not to infer what the trial was designed to achieve.

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 = -2.610; pooled standard deviation σ = 5.825.
2. n = 2 × (1.96 + 0.842)² × 5.825² / -2.610² = 78.2, rounded up to 79 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 <- -2.61                      # observed difference in means
sigma <- 5.82517105564969                     # 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(4279522)
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 = 79 (80% power), 105 (90% power)
 75% of observed effect: n per arm = 140 (80% power), 187 (90% power)
 50% of observed effect: n per arm = 313 (80% power), 419 (90% power)
power.t.test: 79.2 
Simulated power at n = 79 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

Multiplicity arises when a study evaluates several outcomes, comparisons, time points, or analysis choices. General: each additional statistical test can increase the chance of obtaining at least one apparently strong result by chance alone. Investigators may address this through a prespecified hierarchy, an adjustment to the testing procedure, or by explicitly treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or an adjustment to the posted p-values. The primary p-value and secondary p-values should therefore be understood as unadjusted values.

Missing data can also affect interpretation. If participants do not have an outcome measurement at the planned assessment, the analysis method determines how much information is retained and what assumptions are made about the unobserved measurements. The registry record does not report the amount or pattern of missing primary outcome data, reasons for missingness, imputation methods, or sensitivity analyses. The posted endpoint group sizes are 47 for active stimulation and 50 for sham stimulation; the record does not explain how those analysis sizes arose from the listed enrollment of 124.

The primary endpoint population is labelled mITT, but the registry does not define that term for this trial. It is not reported whether the analysis included all randomized participants, which eligibility or treatment conditions were applied, or how participants without an endpoint measurement were handled. As a result, the relationship between randomization and the analyzed population cannot be fully assessed from the posted record.

The registry also does not report whether there were interim analyses, a stopping rule, or changes to the analysis plan. The absence of these details in the record is not evidence that such procedures did or did not occur. Without those methods, readers cannot determine whether the posted analysis followed a prespecified plan or how alternative reasonable decisions might affect the estimates. These uncertainties do not erase the reported results, but they limit how completely they can be evaluated.

15. 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: worsening of depression symptoms (1.0%).

The posted serious adverse event figures are reported separately for active stimulation, sham stimulation, and the open-label active-stimulation period. For each randomized group, 62 participants are listed as at risk; serious adverse events affected 0 in the active-stimulation group and 0 in the sham-stimulation group. For open-label active stimulation, 96 are listed as at risk and 1 serious adverse event was reported. The record lists no deaths in any of these groups.

The serious-event term identified in the record is worsening of depression symptoms, reported as 1.0%. These figures should be read as the registry’s posted event counts and category, not as a complete characterization of safety. The record does not provide event timing, duration, severity details beyond the serious-event classification, or a narrative account of the open-label event. It also does not explain the relationship between the at-risk counts and the endpoint analysis populations.

The figures for non-serious adverse events are recorded separately from serious adverse events and should not be conflated with them. In general, the absence of a reported serious event in a group does not establish that no risk exists; it describes only what was reported in that group and observation period. The registry data alone do not establish comparative safety or identify uncommon risks.

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

The primary posted result describes a greater average decline in HDRS17 total score in the active-stimulation group than in the sham-stimulation group by the 8-week assessment. The estimated mean difference was -2.61, and the reported interval lies below zero. The unadjusted p-value was 0.027. These statistics characterize the observed comparison and its uncertainty under the analysis assumptions.

The result does not mean that every participant’s score declined, or that all participants experienced a similar change. Group means can conceal variation among individuals. The registry reports standard errors for group means, but does not report participant-level distributions or explain the missing-data process. Nor does the result establish the duration of any change beyond the stated assessment. The open-label active-treatment phase is described in the study summary, but the posted primary comparison is at 8 weeks and does not establish a randomized active-versus-sham contrast throughout the open-label period.

The result also does not by itself establish the clinical importance of the estimated difference. The registry record does not report a threshold for a clinically meaningful HDRS-17 difference, and statistical evidence for a difference is not identical to evidence that the difference matters to patients. The reported secondary results provide additional symptom measures, but they are unadjusted and vary in precision; they should not be treated as multiple independent confirmations.

Finally, a registry result is not a complete account of trial conduct or analysis. The mITT definition, missing-data procedures, original sample-size justification, multiplicity strategy, and detailed statistical methods are not reported in the registry record. Those omissions prevent a full assessment of robustness and limit conclusions about generalizability. The appropriate reading is therefore specific: the posted data show a negative between-group mean difference in HDRS17 change at the stated time point, with an interval and unadjusted p-value that indicate statistical separation under the reported analysis, while clinical meaning and broader implications require information not reported in the registry record.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized sham-controlled comparison is different from observing change in an active-treatment group alone. Both posted groups had a negative mean change in HDRS17 score. Comparing their changes accounts for the fact that symptom scores may shift in either group during the study period. The primary mean difference is therefore the central estimate for the randomized comparison, rather than the active-group change considered in isolation.

It also demonstrates the value of reading effect estimates with intervals. The estimate gives the direction and size of the average difference, while the interval conveys uncertainty around that estimate. A p-value alone would not show the range of values compatible with the analysis or distinguish statistical evidence from clinical importance. The posted primary comparison has an interval below zero, while secondary results show less consistent precision, making it important not to treat every endpoint as equivalent evidence.

The record is also a useful example of registry interpretation limits. A completed trial has posted group summaries, yet key methodological details—including the mITT definition, missing-data handling, multiplicity plan, and original sample-size rationale—are not reported in the registry record. Such gaps matter because they affect how readers judge selection of the analysis population, robustness to missing outcomes, and the strength of claims across multiple endpoints.

Finally, planning figures based on observed effects are not a substitute for the trial’s original design calculation. Their value is in illustrating how smaller target effects and higher desired power affect the number of participants needed per arm under stated assumptions. Keeping that planning exercise separate from the observed trial result helps avoid treating post hoc planning calculations as evidence about the trial’s actual power.

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.

Several limitations specific to this registry record constrain interpretation. The primary outcome is reported for an mITT population, but the record does not define that population. It lists enrollment of 124 while the primary result reports group sizes of 47 and 50; the record does not explain the relationship between these figures or describe missing endpoint data. This leaves uncertainty about participant inclusion and outcome availability.

The record gives no trial-specific account of how the primary interval was constructed and does not identify its confidence level. It also does not report covariate adjustment, sensitivity analyses, or whether analysis choices were prespecified. Although the study summary describes quadruple masking in the design fields and double-blind in its narrative, the record does not reconcile those terms or identify the masked roles.

For the secondary outcomes, no multiplicity adjustment or testing hierarchy is reported. The registry lists three secondary measures and an outcome-measure count of seven, without explaining the difference. The listed reported-analyses collections for the secondary outcomes are empty, although summary group values and comparisons are posted. This limits the ability to assess completeness and prespecification of the secondary reporting.

The primary endpoint is measured at 8 weeks; the registry record does not establish longer-term randomized comparative results. Although an open-label active-treatment period is described, the posted primary result does not answer whether the active-versus-sham difference persists over that later period. The record also does not provide a clinical-importance threshold for HDRS-17, details of event timing for safety outcomes, or information that would establish the applicability of findings beyond the study population.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD) — NCT04279522.
• Registry record last updated 2025-08-12; status last verified 2025-07.
• Results first posted 2025-08-12.
• 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 MOOD Study is a completed randomized, parallel-group comparison of Relivion®DP active stimulation and sham stimulation for major depressive disorder. Its primary endpoint is mean change in HDRS17 total score from baseline to 8 weeks, analyzed in a population identified as mITT. The posted active-versus-sham mean difference is -2.61, with a reported interval from -4.929 to approximately -0.291 and an unadjusted p-value of 0.027.

Secondary outcomes cover response, remission, and MADRS change. Their estimates vary in precision, and the registry record does not report a multiplicity strategy. The record also does not define the mITT population, explain missing data, or provide the original sample-size justification and full statistical plan. Safety listings report no serious adverse events in either randomized group and 1 in the open-label group. These results describe the posted data; the registry record leaves important methodological and clinical interpretation questions unresolved.