Theta Burst Stimulation in Young Adults With Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Theta Burst Stimulation in Young Adults With Depression (NCT03737032), a randomized na study. The primary outcome is Dorsomedial Prefrontal Cortex Activation.

2. Clinical Question

This question concerns an acute brain-function measure rather than a reported clinical symptom or longer-term outcome. The primary measure was a blood oxygen level dependent response obtained with task fMRI. Higher values represent higher activation, but the scale is in arbitrary units and has no theoretical minimum or maximum. The registry record reports an overall ANOVA comparison of the three stimulation conditions and also permits simple, unadjusted comparisons of each active condition with sham using posted summary statistics. Those analyses answer related but not identical questions: the overall analysis concerns whether the three conditions differ, whereas the two pairwise recalculations focus on each active condition versus sham.

3. Trial Design

This was a randomized, double-masked crossover study marked completed in the registry record. Its enrollment is 29. The study summary describes a proposed 2-year, within-subject investigation in young adults with depression, with participants receiving all three conditions: intermittent theta burst stimulation, continuous theta burst stimulation, and sham theta burst stimulation. The primary outcome description says task fMRI was conducted after each session. Sessions were scheduled at approximately 3, 5, and 7 weeks after study entry.

The registry lists six possible orders of the three sessions. Each order includes intermittent, continuous, and sham stimulation, with the order varied across sequences. The record describes this arrangement as randomized and counterbalanced. A crossover design lets each participant contribute data under more than one condition, so comparisons can potentially account for within-person differences. The posted group summaries do not include the individual paired measurements or within-person correlations needed to reconstruct such an analysis independently.

The primary analysis population included cases from participants who completed all study procedures, including all TMS sessions and all MRI scans, had available data, and passed data quality criteria. The reported arm summaries show 10.0 observations for each condition. Those analysis counts should not be confused with registry enrollment or the enrollment target described in the study summary. The record does not report the reasons that some enrolled participants may not appear in the primary outcome summaries.

The study lists depression as its condition and identifies functional connectivity and positive affect among secondary outcomes. Its phase is listed as NA. The original design assumptions, including any planned sample-size justification, are not reported in the registry record. The registry record also does not report the detailed masking procedures, the specific randomization mechanism, or how the analysis handled period, sequence, or carryover effects.

4. Participant Flow and Accounting

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

Before assignment: 29 participants completed enrollment in the study. Prior to randomization, all 29 participants completed study visit #1 and study visit #2. Out of those 29, 4 participants were withdrawn after study visit #2 and before randomization. 25 participants were randomized and completed the study intervention.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Cases included in analysis are those from participants who completed all study procedures (i.e., all TMS sessions, all MRI scans), had available data, and passed data quality criteria

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dorsomedial Prefrontal Cortex Activation, measured over Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order) at approx 3, 5, and 7 weeks after study entry..

The primary endpoint is dorsomedial prefrontal cortex activation during a reward task. It is measured using the blood oxygen level dependent response from functional magnetic resonance imaging, with data analyzed using Statistical Parametric Mapping. The reported measure is a mean score in arbitrary units; higher values indicate higher activation. Because the score has no theoretical minimum or maximum, it is not naturally interpreted as a bounded clinical scale.

This endpoint is used to assess brain function in the dorsomedial prefrontal cortex after each stimulation session. The study summary describes the aim as examining acute effects of theta burst stimulation on function in this region. That makes the endpoint relevant to the study's mechanistic question about whether stimulation conditions are associated with different brain responses. It does not, by itself, measure depression symptoms, everyday functioning, or durability of any change.

The posted summaries give means and standard deviations for each stimulation condition. The primary outcome description specifies that the analysis population consisted of participants who completed all procedures, had available data, and met data quality criteria. The registry record does not report a clinically meaningful threshold for interpreting a change in this arbitrary-unit measure. Consequently, the endpoint can describe the direction and uncertainty of measured activation differences, but the record alone does not establish the clinical importance of any observed difference.

7. Results Posted in the Registry

• Intermittent TBS: mean 0.16 versus 0.36 on control; difference -0.20 (95% CI -3.44 to 3.04), standardized effect d = -0.05; z-test p = 0.904.
• Continuous TBS: mean 1.35 versus 0.36 on control; difference 0.99 (95% CI -2.49 to 4.47), standardized effect d = 0.25; z-test p = 0.577.

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.

VS-dmPFC Functional Connectivity

• 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:
  • Intermittent TBS: mean 2.28 versus 1.16 on control; difference 1.12 (95% CI -4.75 to 6.99), standardized effect d = 0.17; z-test p = 0.709.
  • Continuous TBS: mean 4.10 versus 1.16 on control; difference 2.94 (95% CI -6.24 to 12.12), standardized effect d = 0.28; z-test p = 0.530.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Intermittent TBS 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 Continuous TBS and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcome results follow a broadly similar pattern to the primary findings: the registry-reported overall comparison for VS-dmPFC functional connectivity is not statistically significant, and the simple pairwise recalculations have intervals that include zero. The secondary endpoint summaries do not offer a clear, precise contrast that changes the overall interpretation of the primary endpoint. Positive affect is listed as a secondary outcome, but its numerical results are not reported in the registry record.

These outcomes relate to the primary result by addressing additional measures associated with the study's brain-function and affective questions. They do not replace the primary endpoint, which was dorsomedial prefrontal cortex activation during the reward task. Nor can consistency across measures establish a clinical effect: the outcomes are different measures, and the registry record does not report a clinical threshold or detailed analysis plan that would connect them to a patient-level benefit.

Unadjusted secondary results generally carry less weight because examining multiple outcomes and comparisons increases the chance of obtaining apparently notable results by chance. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized, or whether these analyses were designated confirmatory or exploratory. In the absence of those details, secondary p-values are best regarded as supportive descriptive evidence rather than independent confirmation. The unreported numerical results for positive affect also prevent a full assessment of the pattern across every listed secondary measure.

The crossover design may be useful for comparing conditions within participants, but the posted summaries do not supply the paired data required to evaluate the secondary outcomes through an independent reconstruction of that design. As with the primary outcome, the recalculations offer simple unadjusted contrasts and do not establish that conditions are equivalent or that an effect is absent.

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

• Positive Affect
• VS-dmPFC Functional Connectivity

9. Statistical Interpretation

10. Statistical Methods Explained

What does the overall ANOVA test address?

ANOVA is a method for assessing whether the means across multiple conditions show evidence of differences. In this study, the registry reports an ANOVA involving intermittent, continuous, and sham stimulation for the primary endpoint, with p = 0.80. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of a difference. The registry record does not provide the ANOVA model details, its test statistic, degrees of freedom, or an interval estimate for the overall comparison.

What do the pairwise recalculations add?

The recalculated comparisons use sham as the reference and estimate a mean difference for each active stimulation condition. For intermittent TBS versus sham, the estimate is -0.2, with a 95% confidence interval from -3.44 to 3.04 and p = 0.904. For continuous TBS versus sham, the estimate is 0.99, with a 95% confidence interval from -2.486 to 4.466 and p = 0.577. These are unadjusted recalculations from posted summary statistics, not the sponsor's reported overall ANOVA. They focus on two particular contrasts and do not test exactly the same hypothesis as the overall three-condition analysis.

A mean difference expresses the estimated difference in average score between the named condition and sham, in the endpoint's arbitrary units. Its sign indicates the direction of that contrast according to the stated ordering. The confidence interval conveys uncertainty in the estimated contrast; when it spans zero, the summaries are compatible with effects in either direction at the conventional interpretation of that interval. Here, both pairwise intervals span zero and include a range of possible values. This should not be translated into proof of no difference.

Why does the crossover design matter?

In a crossover design, participants receive multiple conditions, making each participant's observations potentially related. An analysis that uses the within-person structure can account for participant-level differences and may use the pairing information. The posted condition-level means and standard deviations do not include the individual paired observations or the covariance between conditions. The simple recalculations use two-condition summary comparisons and cannot recover that within-person structure. The registry record identifies the study as a crossover but does not report enough model detail to determine exactly how the sponsor's ANOVA handled repeated measurements, sequence, period, or possible carryover.

This distinction matters because the precision of a paired contrast depends partly on how strongly measurements from the same person are related. Separate condition standard deviations alone do not reveal that relationship. Consequently, the recalculated standard errors, p-values, and intervals are not a reconstruction of a full crossover model. They give a transparent, unadjusted reading of the posted summaries, while the registry's own reported analysis remains the sponsor-reported result.

How should standard deviations and standard errors be read?

A standard deviation describes the spread of measurements among the observations in a condition. A standard error describes uncertainty in an estimated quantity, such as a mean, under the assumptions used to calculate it. The posted primary standard deviations range from 3.6 to 4.3, while the recalculation lists standard errors for the condition means and contrasts. These quantities answer different questions: spread among observations is not the same as uncertainty in the mean difference.

General statistical context: when outcome variability is large relative to the difference being estimated, the data may give a broad interval and have limited ability to distinguish plausible effects. In this study, the primary contrast intervals are wide relative to their point estimates. That limits how specifically the simple recalculations locate the underlying difference. This observation describes precision, not the probability that any particular effect is true.

What do the secondary analyses show methodologically?

The registry reports a separate ANOVA for VS-dmPFC functional connectivity, with p = 0.84. Pairwise unadjusted recalculations are also available for that continuous outcome. The analyses use mean differences and confidence intervals, a familiar way to express the scale and uncertainty of a continuous outcome. Positive affect is named as a secondary outcome, but numerical results for it are not reported in the registry record.

Multiple outcomes and contrasts create multiple opportunities to observe small p-values by chance when each is assessed separately. Whether the analysis plan used a multiplicity adjustment is not reported in the registry record. Without that information, the unadjusted secondary p-values should be treated as exploratory rather than as standalone confirmatory evidence. The registry record does not report a prespecified hierarchy among the outcomes or a detailed statistical analysis plan.

General statistical context: over-dispersion means that observed variability is greater than a model expects. It can make standard errors too small if the model fails to account for that extra variability. The registry record does not report an over-dispersion assessment, and the posted outcomes are continuous measures summarized by means and standard deviations. It would therefore be inappropriate to assert that over-dispersion was present or that a particular correction was used.

11. Confidence Intervals and Precision

A confidence interval is a range of values compatible with the data and the method used to calculate it. General statistical interpretation: a wider interval indicates less precision, while a narrower interval indicates a more concentrated estimate. A confidence interval is not a guarantee that the true value lies inside that particular calculated range, and it does not assign probabilities to individual values within the interval.

For the primary endpoint, the recalculated intermittent-versus-sham mean difference is -0.2, with a 95% confidence interval from -3.44 to 3.04. The interval includes zero and spans negative and positive differences. The continuous-versus-sham estimate is 0.99, with a 95% confidence interval from -2.486 to 4.466; this interval also includes zero and values in both directions. These ranges indicate that the simple recalculations do not sharply determine either contrast's direction or magnitude.

The width of the intervals should be considered alongside the outcome's arbitrary-unit scale and the reported standard deviations. The registry record does not identify a clinically meaningful difference for this measure, so it is not possible from these summaries to determine whether particular values within an interval would be clinically important. Nor do the intervals establish equivalence or rule out effects of meaningful size.

The intervals belong to unadjusted recalculations from summary statistics. Because the study is a crossover and the summaries do not include participant-level pairing information, they do not reflect a reconstructed within-person analysis. The registry-reported ANOVA does not include an interval estimate in the posted results. Thus, the recalculated intervals are useful for illustrating the uncertainty in simple contrasts, but they should not be mistaken for the sponsor's full crossover-model uncertainty estimates.

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 illustrations are expressed as participants per arm, not as total events. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These are planning illustrations computed from the observed effect, not the original design assumptions for this trial; the trial's own design assumptions are not reported in the registry record. This is not observed power.

The 80% power column gives an illustrative participants-per-arm requirement for a future two-arm study to have an 80% chance of detecting the assumed effect under the listed planning assumptions, if that effect and those assumptions were correct. The 90% power column gives the corresponding illustration for a 90% chance. Power is a design property under specified assumptions, not a result measured after the trial.

The rows consider planning for 100%, 75%, and 50% of the observed effect. A smaller target effect requires more participants because a smaller separation is harder to distinguish from ordinary variability. For example, for continuous TBS versus sham, planning for 100% of the observed effect gives 252 participants per arm for 80% power and 338 for 90% power; planning for 50% gives 1,008 per arm for 80% power and 1,349 for 90% power. For intermittent TBS versus sham, the corresponding 100% illustration is 5,362 participants per arm for 80% power and 7,178 for 90% power. These figures are especially sensitive to the small observed contrasts used as their starting point.

The illustrations assume a two-arm equal-allocation comparison, whereas the trial itself used a three-condition crossover. They are not direct forecasts of the sample size needed for an equivalent crossover analysis. The planning curve should be read in the same conditional way: it shows how the illustrative requirement changes as the target effect is varied, not how many participants this completed study should have enrolled.

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 = -0.200; pooled standard deviation σ = 3.696.
2. n = 2 × (1.96 + 0.842)² × 3.696² / -0.200² = 5,361.6, rounded up to 5,362 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 <- -0.2                      # observed difference in means
sigma <- 3.69622104317369                     # 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(3737032)
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 = 5,362 (80% power), 7,178 (90% power)
 75% of observed effect: n per arm = 9,532 (80% power), 12,761 (90% power)
 50% of observed effect: n per arm = 21,447 (80% power), 28,711 (90% power)
power.t.test: 5362.5 
Simulated power at n = 5,362 per arm: 0.794 (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 registry-reported primary analysis is an ANOVA across the three stimulation conditions, with p = 0.80. That is the sponsor-reported result for the primary endpoint. The record does not include an estimated overall difference, confidence interval, or detailed model specification for this analysis.

The recalculations compare each active condition separately with sham using posted means and standard deviations. They report an intermittent-versus-sham mean difference of -0.2 with p = 0.904, and a continuous-versus-sham mean difference of 0.99 with p = 0.577. These calculations are unadjusted and do not reconstruct the within-person crossover model. They therefore provide a supplementary, transparent look at simple contrasts rather than a substitute for the reported ANOVA.

The registry indicates no discrepancy between the reported analysis and the recalculations. Even so, their p-values should not be expected to match because the overall ANOVA and the separate pairwise calculations test different hypotheses and use different summaries. The crossover structure is also relevant: participant-level paired data and model details are not available in the posted summaries. Interpretation should therefore retain the sponsor's ANOVA as the reported analysis while using the recalculations only to understand the approximate pairwise differences and their uncertainty.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, with three reported analyses in the record. It reports an overall ANOVA for the primary outcome and another overall ANOVA for VS-dmPFC functional connectivity. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a detailed statistical analysis plan describing how the several outcomes and comparisons were to be interpreted.

Multiplicity matters because testing several outcomes or contrasts can increase the chance of at least one apparently significant result even when no real effect exists. General statistical context: adjustments or prespecified testing hierarchies can help control that risk, but the record does not establish that any particular approach was used. Pairwise recalculations are explicitly unadjusted, so their p-values should not be treated as multiplicity-controlled confirmatory tests.

The primary analysis population is defined by completion of all study procedures, availability of data, and passing data quality criteria. This is a restricted analysis population, not a description of all enrolled participants. The registry record does not report how many participants failed each criterion, the reasons for missing outcome data, whether excluded participants differed from included participants, or whether a missing-data method was used. It also does not report an intention-to-treat analysis or sensitivity analyses for missing data.

Because the study is a crossover, the analysis may need to account for repeated measurements and the order and timing of conditions. The registry record describes randomized, counterbalanced session orders but does not report whether the model included period or sequence effects, how possible carryover was assessed, or how within-person dependence was handled. Those omissions limit the ability to evaluate whether the reported model fully reflects the design. They do not establish that the analysis was inappropriate; they mean that the relevant details are not reported in the registry record.

The primary outcome description also specifies data quality criteria, but those criteria and their application are not detailed. Without information about exclusions and missingness, it is difficult to assess the potential for selection effects in the analyzed cases. The posted summaries should therefore be interpreted as applying to the stated analysis population rather than automatically to every person enrolled.

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 4% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record gives 25 participants at risk in each of the intermittent, sham, and continuous groups. It reports zero serious adverse events and zero deaths in each group. For other adverse events, it reports zero affected participants for intermittent and sham stimulation, and 1 affected participant for continuous stimulation. These are the event figures recorded for the listed groups.

These entries describe what was reported in the registry safety fields; they do not establish that no unrecorded or unmeasured events occurred. The record does not provide details about the nature, timing, severity, or relatedness of the other event recorded for continuous stimulation. It also does not describe how adverse events were collected or adjudicated.

The adverse-event denominators differ from the condition analysis counts reported for the primary outcome. The safety figures should therefore be read in their own registry context and not treated as interchangeable with the primary efficacy analysis population. Because this was a crossover study, the safety entries should not be used to infer independent parallel-group comparisons without additional detail on the event collection and analysis approach.

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

The posted results describe brain activation and functional connectivity measured around stimulation sessions, not a demonstrated change in depression symptoms or long-term functioning. The registry's primary endpoint is an imaging-based measure in arbitrary units. The study summary describes the investigation as examining acute effects, and the record does not report a clinical threshold that would make a particular difference on this scale meaningful to patients.

The sponsor-reported overall primary analysis has p = 0.80. The simple recalculated comparisons with sham are imprecise: their confidence intervals include zero and extend in both directions. These findings do not establish a clear difference between conditions. They also do not prove that the conditions have identical effects or exclude every potentially meaningful difference. The evidence is limited by the available analysis counts, variability, and the breadth of the intervals.

The stated hypothesis predicted a decrease in dorsomedial prefrontal cortex activation after continuous TBS. The posted mean for continuous stimulation is above the sham mean, but the recalculated interval includes both negative and positive differences. The summaries therefore do not establish the predicted decrease, but they are also too imprecise to support a firm conclusion that a different direction is present.

General statistical context: a non-significant test can arise when an effect is small, when measurements are variable, or when the analysis has limited precision. It is not a direct test of equivalence. Establishing equivalence would require a prespecified acceptable range and an analysis designed to assess whether the uncertainty lies within that range; such a range is not reported in the registry record.

These results should not be interpreted as advice about treatment or as evidence of clinical effectiveness. The registry record supports conclusions about the reported imaging measures, study conditions, and their statistical uncertainty. It does not report symptom outcomes in a way that establishes patient benefit, nor does it establish persistence of effects beyond the measured sessions.

18. Why This Trial Matters Statistically

Statistically, this study is informative because it combines a randomized, counterbalanced crossover design with repeated imaging after distinct stimulation conditions. A crossover can make within-person comparisons relevant by allowing a participant to experience each condition. It also creates analysis requirements: measurements from the same person are related, and period and sequence can matter. The registry identifies the design but does not report enough model detail to evaluate how those features were addressed.

The results illustrate why point estimates, intervals, and analysis design should be read together. The primary recalculated contrasts have point estimates near zero relative to broad intervals, while the overall reported ANOVA is non-significant. A p-value alone cannot communicate the range of plausible contrast values or distinguish a well-estimated small effect from an imprecisely estimated effect. The interval summaries make that uncertainty visible, although they do not reproduce the full crossover analysis.

The sample-size illustrations also show how planning depends on the assumed target effect. They are derived from observed contrasts and use a two-arm planning framework, rather than representing the original study's design calculation or a direct design analogue for this crossover trial. Their large variation across effect scenarios underscores that sample-size planning is conditional on assumptions, not a retrospective verdict on whether the completed study was adequately powered.

Finally, the record distinguishes a mechanistic imaging endpoint from clinical outcomes. This helps readers avoid treating a measured brain response as interchangeable with symptom improvement. Statistical interpretation depends not only on whether a test crosses a conventional threshold, but also on the endpoint, study structure, uncertainty, missing information, and the question the analysis was designed to answer.

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 primary analysis includes only participants who completed all TMS sessions and MRI scans, had available data, and passed data quality criteria. The registry record does not report exclusions by reason, missing-data handling, or sensitivity analyses. This makes it difficult to judge how the analyzed cases relate to all enrolled participants.

The registry enrollment is 29, while the study summary describes a proposed investigation involving 35 young adults. The posted primary outcome summaries list 10.0 observations in each condition. The record does not explain the relationship between the proposed number, enrollment, and the reported analysis counts, so these quantities should not be treated as interchangeable.

Although the design is crossover, the posted summaries do not include paired participant-level data. The independent two-condition recalculations cannot capture within-person correlations, and the registry does not provide the detailed ANOVA model needed to assess treatment of repeated measurements, sequence, period, or carryover. The recalculated intervals and p-values are consequently limited approximations to the condition contrasts.

The primary measure is in arbitrary units and has no reported clinically meaningful threshold. No numerical positive affect results are reported in the registry record. The record also does not report multiplicity handling, the detailed statistical analysis plan, or the original sample-size assumptions. These gaps limit evaluation of confirmatory status, clinical importance, and the basis for the trial's design.

The safety record gives event counts but does not describe event type, timing, severity, attribution, or collection procedures. Together, these limitations mean the posted data support cautious interpretation of the reported measures, rather than broad conclusions about clinical outcomes or the full safety profile.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Theta Burst Stimulation in Young Adults With Depression — NCT03737032.
• Registry record last updated 2024-03-19; status last verified 2024-02.
• Results first posted 2024-03-19.
• 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 NCT03737032, titled Theta Burst Stimulation in Young Adults With Depression. It is marked completed and identifies depression as the condition. The listed design is randomized, double-masked, and crossover, with intermittent TBS, continuous TBS, and sham TBS delivered in randomized, counterbalanced session orders. The study summary describes young adults aged 18-25 and a proposed 2-year investigation.

The primary endpoint is dorsomedial prefrontal cortex activation during a reward task, measured by task fMRI after stimulation sessions. The registry-reported primary analysis is an ANOVA with p = 0.80. Simple recalculated comparisons with sham have confidence intervals that include zero and are broad relative to their point estimates. These results do not establish a clear condition difference, while the available uncertainty does not establish equivalence.

The registry lists functional connectivity and positive affect as secondary outcomes. It reports an overall functional-connectivity ANOVA and does not report numerical positive affect results. The record does not report the original design assumptions, detailed analysis model, multiplicity handling, or missing-data sensitivity analyses.