iTBS Study for Depression (Randomized): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for iTBS Study for Depression (Randomized) (NCT03745768), a randomized na study. The primary outcome is Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores From Baseline to the End of the Intervention.

2. Clinical Question

The clinical rationale in the record is that executive-function deficits commonly accompany late-life depression and are associated with poorer outcomes and disability. The study was intended to examine mood and executive function, and to test effects on brain connectivity within the Cognitive Control Network. Those aims describe the motivation and scope of the study; they do not establish that the intervention changed any of these outcomes.

The primary outcome is specifically a change in MADRS score across the intervention period. The registry record describes the scale as a measure of depressive symptoms, with a total score ranging from 0 - 60 and lower scores indicating fewer symptoms. The posted outcome values are reported by arm, without a confidence interval or a statistical test comparing the arms. The meaning of a positive or negative change is not specified in the record, so the means alone should not be read as the size or direction of improvement.

3. Trial Design

The study is recorded as randomized, quadruple-masked, and parallel, with active iTBS and sham stimulation as the two arms. In a parallel design, participants are assigned to one group for the comparison rather than receiving both study conditions in sequence as treatment periods. Random assignment is intended to make the groups comparable on average, although it cannot ensure balance in every characteristic, particularly in a small study.

The registry record lists 19 participants enrolled. Its brief description says 20 subjects would be randomized, while the enrollment field reports 19; why these figures differ is not reported in the registry record. For the posted primary outcome, the active iTBS arm has 8 participants and the sham arm has 9. The record does not explain why these outcome counts are smaller than the enrollment figure. The adverse-event summaries use at-risk counts of 10 for active iTBS and 9 for sham stimulation, so the denominators differ by outcome type.

Active and sham stimulation were administered to the dorsolateral prefrontal cortex for 6 weeks. The brief description specifies a Monday-Friday schedule and says stimulation was applied sequentially to the left and right sides, with total stimulation time of about 7 minutes. The arm descriptions separately state that each group received its assigned stimulation for 6 weeks. The record does not give further operational details about treatment delivery or adherence.

The study status is completed. The recorded start date is 2018-04-05 and the primary completion date is 2020-04-01. The phase is listed as NA. Washington University School of Medicine is identified as sponsor. Although the record describes quadruple masking, it does not identify which groups of people were masked or explain how masking was maintained. These design details affect how readers assess possible performance and assessment biases, and remain unresolved from the registry entry.

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:

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 Montgomery-Asberg Depression Rating Scale (MADRS) Scores From Baseline to the End of the Intervention, measured over 6 weeks.

The primary endpoint is change in the Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline to the end of the intervention, with a timeframe of 6 weeks. MADRS is used in this study to measure mood and depressive symptoms. The registry description says the total score ranges from 0 - 60, with 0 as the minimum and 60 as the maximum; a lower score denotes fewer depressive symptoms.

A change score is intended to express how a participant’s measurement differs between two assessment times. Comparing changes between randomized arms can focus the question on whether the groups followed different trajectories over the intervention, rather than only comparing a single endpoint measurement. That is a general explanation of change-score outcomes. The record identifies the endpoint as a change from baseline but does not specify the subtraction convention or whether the posted values are signed changes, reductions, or another representation. Therefore, the arm means should not be assigned a direction of improvement from their signs without further information.

The registry record lists the endpoint as a mean with standard deviation. Those summaries describe the center and spread of the posted arm results. They do not by themselves quantify uncertainty in the difference between groups, establish a statistically detectable effect, or show how individual participants changed. No confidence interval or inferential comparison for this endpoint is reported in the registry record.

The record also describes executive function as an intended study outcome, assessed with the National Institutes of Health Toolbox executive domain battery. However, no secondary outcome results are posted in the record. The primary mood endpoint can therefore be interpreted only as an arm-level descriptive summary, not as a complete account of the study’s other stated aims.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a continuous score and reports each arm’s mean and standard deviation. These are descriptive statistics. The mean gives the arithmetic average of the reported values within an arm, while the standard deviation describes how dispersed those values are around the mean. A standard deviation is not a measure of precision for the mean and is not an interval for the treatment contrast. The arm summaries are 10.25 with standard deviation 6.4 for active iTBS, based on 8 participants, and 13.33 with standard deviation 3.7 for sham stimulation, based on 9 participants.

What would a group comparison estimate?

In general, a two-arm comparison for a continuous outcome estimates how the outcome differs on average between assigned groups. For this trial, the clinical target is the between-arm difference in MADRS change from baseline to the end of the intervention. A point estimate would summarize the observed contrast, and a confidence interval would describe the precision of that estimate under the analysis assumptions. The registry record does not report a point estimate for the contrast or a confidence interval. It also does not report a p-value or a specified inferential test.

General statistical interpretation requires separating the estimated effect from its uncertainty. A confidence interval can show whether the data are compatible with a range of possible effects; its width reflects precision, and its interpretation depends on the study design and method. A p-value, when reported, addresses compatibility with a specified null model, not the probability that a treatment works or the probability that a hypothesis is true. Neither type of inferential result is reported for this primary comparison in the registry record.

Why do the sample sizes matter?

Smaller arm counts generally make estimates less precise, all else being equal. In a small randomized trial, chance imbalances between groups can also occur, and a few observations may have substantial influence on an average. The reported standard deviations describe the observed within-arm spread, but without a comparison estimate and interval they do not indicate how precisely the difference between arms is estimated. The outcome counts are 8 and 9, while enrollment is listed as 19; the reason for the distinction is not reported in the registry record.

The record includes the assumptions for a sample-size planning illustration: a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are planning assumptions, not proof that the trial was designed around them. The registry record does not report the trial’s own sample-size justification. Any sample-size illustrations should be understood as planning scenarios rather than as observed power or as evidence about the study’s actual design rationale. They cannot substitute for an uncertainty interval around the observed treatment contrast.

What does masking contribute?

The study is recorded as quadruple-masked. In general, masking can limit the influence of expectations on treatment delivery, participant reporting, outcome assessment, or analysis. The registry record does not identify which people were masked or detail the masking procedures. It is therefore possible to note the recorded masking designation, but not to assess from this entry which potential sources of bias it addressed or whether masking remained successful.

Randomization and masking are features of design, not statistical results. Random assignment can help support causal comparisons when the analysis follows the intended assignment and outcome data are adequately handled. Masking can reduce some forms of bias. Neither resolves questions about missing observations, outcome coding, adherence, analysis populations, or whether the reported summaries account for all randomized participants. Those details are not reported in the registry record.

How should change scores be read?

In general, a change score is derived from measurements at two times, but interpretation depends on how subtraction is defined and whether the analysis compares raw changes or uses another model. For example, an outcome can be recorded as follow-up minus baseline or in the reverse order; the signs then carry different meanings. The record names change from baseline to the end of the intervention but does not specify the sign convention. It reports means and standard deviations without confidence limits, so the summaries cannot settle the direction or precision of a between-arm effect.

There is also no reported adjusted analysis. A model could, in general, account for baseline measurements or other prespecified factors, but no adjustment variables or model specification are reported in the registry record. It would be inappropriate to assume that an adjusted analysis was performed or to infer its result from arm-level means. The posted summaries support a descriptive account only.

The record lists 6 outcome measures but no secondary outcome results, and it reports no separate statistical analyses. The statistical plan, including any testing hierarchy or multiplicity adjustment, is not reported in the registry record. With no inferential results or detailed analysis methods, the reader cannot determine whether the primary comparison followed a prespecified plan, how missing values were treated, or whether the reported group summaries use an intention-to-treat population. These are distinct questions from the basic calculation of arm means and standard deviations.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active iTBS Treatment", "Sham Stimulation")
n   <- c(8, 9)
m   <- c(10.25, 13.33)
sp  <- c(6.4, 3.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active iTBS Treatment  8  10.250  6.400  4.899  15.601
CARM  Sham Stimulation  9  13.330  3.700  10.486  16.174

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures, but no secondary outcome results are posted. The MADRS change outcome is designated primary. The study description also names executive function and brain connectivity among its aims, but results for those aims are not reported in the registry record. A complete account of outcomes would be needed to assess how the reported primary endpoint relates to all planned analyses.

Multiplicity arises when several outcomes or statistical tests are considered. In general, examining multiple results can increase the chance of a seemingly notable finding occurring by chance, so protocols may specify a primary endpoint, testing hierarchy, or adjustment method. The registry record does not report whether multiplicity was addressed, whether a hierarchy was prespecified, or what testing strategy was used. No secondary inferential results are available in the record to evaluate alongside the primary endpoint.

Enrollment is listed as 19, while the primary outcome summaries use 8 participants in the active iTBS arm and 9 in the sham arm. The reasons for these outcome counts, including whether any participants lacked endpoint data or were excluded from the analysis, are not reported in the registry record. The record also does not report imputation, missing-data assumptions, sensitivity analyses, or the timing and reasons for any missing measurements.

The analysis populations are not described in the registry record. It is not specified whether the summaries include all randomized participants, only participants with observed outcome data, or another defined set. Nor are protocol deviations, adherence criteria, or exclusions from analysis reported. These omissions limit assessment of whether the posted summaries preserve the randomized comparison and how missingness might affect interpretation.

12. 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 5% reporting threshold.

The serious adverse event summaries report 0 events among 10 participants at risk in the active iTBS group and 0 events among 9 participants at risk in the sham group. The record also reports 0 other adverse events in each group and 0 deaths in each group. These figures describe the event counts recorded for the participants counted as at risk; they do not mean that every possible event was ruled out or that no event could occur outside the recorded observation period.

In general, a count of zero in a small group is a description of what was recorded, not proof that the underlying event risk is zero. Estimates of rare-event risk are especially uncertain when few people are observed. The registry record does not provide an adverse-event observation timeframe, event narratives, or details about how events were collected. It lists no serious adverse-event terms. The safety denominators also differ from the primary outcome counts, and the reasons for that difference are not reported in the registry record.

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

The result consists of descriptive arm summaries for the primary outcome: a mean of 10.25 and standard deviation of 6.4 for active iTBS among 8 participants, and a mean of 13.33 and standard deviation of 3.7 for sham stimulation among 9 participants. The endpoint is identified as change in MADRS score from baseline to the end of the intervention. The record does not clarify how the change was coded, and it does not report a statistical comparison or an interval describing uncertainty in the contrast.

These statistics do show what the registry record reports for each group. They do not, on their own, show whether the groups differed in a way unlikely to arise through chance, how large a group difference might plausibly be, or whether any difference would be clinically meaningful. The MADRS scale description says lower scores correspond to fewer depressive symptoms, but the missing change-score convention prevents a confident interpretation of the direction of the posted means as change.

The randomized design is relevant because the study was structured to compare assigned groups. Yet an interpretable estimate also depends on details such as analysis population, handling of incomplete measurements, and the precise outcome calculation. Those details are not reported in the registry record. A completed study status and posted summaries do not resolve these gaps.

The study description includes aims related to executive function and brain connectivity, but no secondary results are posted. The primary summaries therefore do not answer those questions. The safety record reports no serious adverse events, other adverse events, or deaths in the listed at-risk groups, but the small counts and absent details limit what can be concluded from those observations.

In short, the registry record offers a limited descriptive account of the primary endpoint and adverse-event counts. It does not establish that iTBS caused a particular outcome, demonstrate equivalence between active and sham stimulation, or provide a complete account of the trial’s stated aims. Conclusions beyond these posted summaries would require additional analysis and reporting.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a randomized design and a fully reported statistical comparison. Randomization describes how treatment assignment was intended to occur; it does not itself provide an estimate of the difference between groups or quantify uncertainty. Here, the record gives arm-level means and standard deviations for the primary outcome, but no confidence interval, p-value, or inferential comparison. Readers can describe the posted summaries, but cannot determine from them alone how precisely the groups differ.

The small outcome counts make careful interpretation particularly important. Descriptive means can be sensitive to individual observations when groups are small, and chance imbalances remain possible even after random assignment. Standard deviations give information about variation within each arm, but do not show the uncertainty around the between-arm contrast. This is a useful example of why an effect estimate and its precision are both needed for a complete statistical interpretation.

The record also illustrates why endpoint definitions matter. MADRS is a symptom scale for which lower scores indicate fewer symptoms, but the registry does not specify the sign convention for the reported change values. A familiar scale direction does not remove ambiguity in a change score. Clear reporting of the calculation and analysis would make the arm summaries more interpretable.

Finally, a trial can have multiple stated aims while reporting results for only one outcome. The record names executive-function and connectivity questions, yet secondary results are not reported. This limits the scope of any summary and makes the reporting of outcome selection, missing data, and multiplicity important. The statistical value of the study is therefore partly in showing what remains necessary for a transparent comparison: a defined estimand, analysis population, missing-data approach, and uncertainty estimate, none of which is fully described in the registry record.

15. 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 outcome summaries do not include a between-arm estimate, confidence interval, or inferential test. The absence of these statistics prevents assessment of the magnitude and precision of the group contrast. The registry record also does not specify the sign convention for change from baseline, so the direction represented by the posted means is unclear even though lower MADRS scale scores indicate fewer symptoms.

Enrollment is listed as 19, while the brief description says 20 subjects would be randomized. The primary outcome counts are 8 and 9, and the adverse-event at-risk counts are 10 and 9. The reasons for these differences across record entries and outcomes are not reported in the registry record. Participant characteristics, detailed eligibility criteria, adherence, withdrawals, and reasons for missing outcome data are also not reported.

The registry record does not describe the analysis population, missing-data method, adjustment strategy, or statistical model. It does not provide an account of multiplicity procedures or a sample-size justification for the trial itself. Although a planning illustration is described as using the observed effect under stated assumptions, it is not the trial’s design justification and should not be interpreted as observed power.

Only the primary outcome has posted results; secondary results are not reported in the registry record despite the stated interests in executive function and brain connectivity. The record identifies quadruple masking but does not state who was masked or how masking was assessed. Adverse-event summaries have no reported observation timeframe or event detail. Together, these limits mean that the available record supports only a narrow descriptive reading rather than a complete assessment of efficacy, safety, or all study aims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: iTBS Study for Depression (Randomized) — NCT03745768.
• Registry record last updated 2022-07-06; status last verified 2022-06.
• Results first posted 2022-07-06.
• 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.

19. Record Summary

NCT03745768 is a completed randomized, quadruple-masked, parallel study sponsored by Washington University School of Medicine. It compares active intermittent theta burst stimulation with sham stimulation in older adults with depression and executive-function impairment. The recorded start date is 2018-04-05 and the primary completion date is 2020-04-01; the phase is listed as NA.

The primary endpoint is change in MADRS score from baseline to the end of the 6-week intervention. The registry record reports means and standard deviations for 8 participants assigned to active iTBS and 9 assigned to sham stimulation, but no inferential comparison or uncertainty interval. No secondary outcome results are posted. The record also reports 0 serious adverse events, 0 other adverse events, and 0 deaths in each group’s listed at-risk population. Important details about change-score coding, missing data, analysis populations, and the statistical plan are not reported in the registry record.