Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder (NCT04058249), a na na study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events.

2. Clinical Question

3. Trial Design

NCT04058249 is registered as a single-group study of accelerated theta-burst stimulation for inpatients with bipolar disorder. The intervention is named as accelerated intermittent theta-burst stimulation over the right DLPFC. The registry describes the study as open-label and lists masking as NONE. Allocation is NA, consistent with the recorded single-group model rather than a randomized comparison.

The registry lists enrollment of 1 and status TERMINATED. The study start is recorded as 2019-11-01, with primary completion on 2021-12-20. The phase is listed as NA. The sponsor is Stanford University. The treatment-emergent adverse-event endpoint has a timeframe of 6 days. These registry entries describe the recorded design and status; they do not establish why the study was terminated or whether all intended study procedures were completed.

The intervention description says all participants would receive accelerated theta-burst stimulation. There is no untreated, placebo, or active comparator listed. Without a comparison group, changes in outcomes cannot be attributed to the intervention through a between-group contrast. The record does not report further detail about treatment scheduling, the intended analysis population, eligibility criteria, or a sample-size justification.

The registry lists two outcome measures and identifies Young Mania Rating Scale [YMRS] Score as a secondary outcome. It records zero analyses. The planned status of an outcome is not itself evidence that a result was collected, analyzed, or posted. For the primary endpoint, the record gives the measure and timeframe but does not report a result. The reason for termination and any protocol amendments are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events, measured over 6 days.

The primary endpoint is the number of participants with treatment-emergent adverse events, measured over 6 days. It is a participant count: the endpoint concerns how many participants experienced an event, rather than the number of separate event episodes. The registry identifies the unit as participants and the parameter as a count of participants.

Safety outcomes are used to describe adverse events recorded during a study period. A participant count can communicate whether any participants were recorded as affected, but it does not by itself describe the event types, severity, timing, duration, or relationship to treatment. Those details would be needed for a fuller interpretation. The endpoint title does not specify event definitions or criteria for judging whether an event is treatment-emergent; those details are not reported in the registry record.

The endpoint is distinct from the listed secondary outcome, Young Mania Rating Scale [YMRS] Score. The registry does not post an analysis result for either measure. Consequently, the endpoint description identifies what was intended to be counted, but it does not establish the observed treatment-emergent adverse-event count. The safety figures recorded elsewhere in the registry should be read according to their own categories and not treated as a reported result for every aspect of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow?

The registered model is SINGLE GROUP, with allocation listed as NA. This means the record describes one group receiving the intervention rather than a randomized allocation to distinct treatment groups. General statistical explanation: an intervention comparison is most informative when groups are made comparable and outcomes are evaluated across them. Without a concurrent comparator, observed changes cannot be distinguished from changes that might have happened without the intervention. For this reason, a single-group study can describe what was recorded among participants, but it does not provide a randomized estimate of the intervention’s effect relative to another condition.

The registry describes the study as open-label and lists masking as NONE. General statistical explanation: masking is intended to reduce the influence of knowledge about treatment assignment on aspects of study conduct or outcome assessment. In an open-label study, that protection is not present as a registered feature. The record does not report additional procedures that might have been used to standardize or independently assess measurements.

What does a participant count represent?

The primary endpoint is a count of participants with treatment-emergent adverse events, with participants as the unit. A participant-based count differs from an event-based count: one participant can experience more than one event, but a participant count records whether participants were affected. General statistical explanation: counts are most interpretable when the event definition, observation period, and denominator are clear. Here the primary endpoint timeframe is 6 days, but the event definition and detailed endpoint result are not reported in the registry record.

The registry’s safety entries separately identify participants at risk and participants affected for serious and other adverse events, as well as deaths. These categories should not be collapsed into a broader claim about every possible adverse event. The primary endpoint’s treatment-emergent wording and the safety categories are related to safety monitoring, but the registry record does not state that every safety category is interchangeable with the primary endpoint definition.

Why do uncertainty and precision matter?

General statistical explanation: an estimate describes the information observed in a study, while an uncertainty interval describes the range of values compatible with the data under a specified statistical method. Wider intervals indicate less precision. A very limited enrollment generally provides little information for estimating how frequently events might occur in a broader population. The registry record does not report a confidence interval for the posted safety counts or for a treatment effect.

A zero observed count does not mean an event is impossible. General statistical explanation: when few participants are observed, an uncommon event may simply not appear during the observation period. The recorded zero counts are therefore best understood as descriptions of what is entered in this record, not definitive estimates of the chance of an event in other participants or settings.

What is the role of the planning illustration?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is the stated planning unit; for other illustrations, the unit is participants per arm. These assumptions describe a planning exercise, not the registered single-group study design.

General statistical explanation: a sample-size illustration depends on assumptions about the effect to detect, the variability or event pattern, the allocation, and the chosen statistical procedure. Changing assumptions changes the planning result. Such an illustration is not an observed study outcome and is not evidence that the study had a particular probability of finding an effect. The record does not report the study’s own sample-size justification. Planning estimates are not observed power, and they cannot substitute for results from an analysis.

What can be assessed from the posted analyses?

The registry records zero analyses. General statistical explanation: without a posted analysis, readers cannot assess the model used, any adjustment for other variables, the treatment of missing observations, or the uncertainty of an estimated outcome. The record lists two outcome measures, but the presence of registered outcomes does not establish that results were analyzed or reported. The statistical analysis plan and detailed analysis population are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Right DLPFC aiTBS Stimulation")
n      <- c(1)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Right DLPFC aiTBS Stimulation  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary treatment-emergent adverse-event count and the secondary Young Mania Rating Scale [YMRS] Score. It records zero analyses. No analysis results for these outcomes are reported in the registry record. A multiplicity strategy, including any planned distinction between confirmatory and exploratory analyses, is not reported.

General statistical explanation: when several outcomes or statistical tests are evaluated, the chance of obtaining an apparently unusual result by chance can increase. A prespecified approach to multiplicity can clarify how results should be interpreted. Since the record does not report an analysis plan or posted tests, it is not possible to determine whether multiplicity was addressed or whether analyses beyond the registered outcomes were conducted.

Missing-data methods are not reported in the registry record. The record does not explain whether all measurements were collected, how incomplete observations were handled, or whether any imputation or sensitivity analysis was planned. An enrollment entry alone does not establish that outcome data were available for every measure or at every assessment.

The intended analysis population is also not reported in the registry record. The posted safety entries give one participant at risk in each listed adverse-event category, but they do not supply a broader account of inclusion in an efficacy analysis. With zero analyses recorded, there is no posted account of exclusions, protocol deviations, or analytic populations. These gaps limit the ability to evaluate how the planned outcomes were translated into statistical results.

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 0% reporting threshold.

The registry’s safety entries list 1 participant at risk for serious adverse events and 0 affected. For other adverse events, the entry also lists 1 participant at risk and 0 affected. Deaths are recorded as 0, and no serious adverse-event terms are listed.

These are counts in a study with enrollment of 1. They describe the safety categories as recorded, not the full range of possible adverse-event experiences. In particular, a zero affected count does not establish that the chance of an event is zero. General statistical explanation: with very limited observation, an event may not appear even when it could occur in a wider population or over a different observation period.

The primary endpoint is worded as the number of participants with treatment-emergent adverse events over 6 days, but the registry does not report a result for that endpoint. The serious and other adverse-event entries should therefore be read as the posted safety figures, not as a complete substitute for a primary endpoint result. Event definitions, collection procedures, and additional event details are not reported in the registry record.

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

The record documents a terminated, open-label, single-group study of accelerated intermittent theta-burst stimulation over the right DLPFC, with enrollment of 1. It identifies the intended primary endpoint as a count of participants with treatment-emergent adverse events over 6 days and lists YMRS Score as a secondary outcome. It also records zero analyses. These registry entries describe the registered study and the limited posted outcome information.

The posted safety entries show 0 affected for serious adverse events and 0 affected for other adverse events among 1 participant at risk in each category, with 0 deaths. Those entries do not amount to a complete reported analysis of the primary endpoint, whose result is not reported in the registry record. Nor do they provide an estimate of event frequency that can be generalized confidently beyond the recorded participant.

The study does not include a registered comparator group. As a result, the record does not support a randomized comparison or a causal estimate of treatment effect. The secondary YMRS outcome has no reported analysis result, so the record does not provide a statistical estimate of change in that measure. No interpretation of efficacy can be drawn from the intervention description alone.

General statistical explanation: an absence of a reported result is different from a result showing no change or no effect. Likewise, a count of zero in a limited safety record is not evidence that an event cannot occur. Conclusions require reported outcome data, an analysis that matches the design, and an account of uncertainty and missing information. Those elements are not available in the registry record. The information supports a cautious description of study conduct and recorded safety counts, not a conclusion that the intervention is effective, ineffective, safe, or unsafe.

14. Why This Trial Matters Statistically

This study is statistically notable because the registered design and the scope of the posted information make the limits of inference especially clear. It is a single-group, open-label study with enrollment of 1, and the registry records zero analyses. The registry lists a primary safety endpoint and a secondary symptom measure, but does not report analysis results for either. The study status is TERMINATED.

General statistical explanation: trial design determines which comparisons can be made. A single-group study may document experiences during exposure, but without a comparator it cannot distinguish intervention-associated changes from other time-related or contextual changes. A very small enrollment also leaves little information with which to characterize variation across participants or estimate event frequencies precisely. These are design and information constraints, not findings about whether the intervention has an effect.

The safety entries also illustrate an important interpretive distinction. Recorded counts of zero are observations within a limited record; they are not guarantees about risk in other participants or settings. Without detailed event definitions, a reported primary endpoint result, or an uncertainty analysis, the safety profile cannot be characterized comprehensively from these entries alone.

The planning framework described in the record is separate from the study itself. It uses assumptions for a two-arm planning illustration, while the registered study is single-group. General statistical explanation: planning calculations depend on assumed design features and effect sizes, and do not serve as evidence that a study had adequate power or that an effect was observed. The record does not report its own sample-size justification. Taken together, these details show why distinguishing registered intent, posted observations, and analyzed results is essential when reading clinical trial records.

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.

Several limitations specific to this record constrain interpretation. Enrollment is listed as 1, and the design is single-group with allocation listed as NA. There is no registered control group for comparison. The study is open-label, with masking listed as NONE. These features limit the ability to make comparative or causal conclusions from outcomes.

The study status is TERMINATED, but the reason for termination is not reported in the registry record. The record gives a primary completion date of 2021-12-20, but does not explain whether all planned procedures or outcome assessments were completed. The protocol details, eligibility criteria, treatment schedule, and any amendments are not reported in the registry record.

The primary endpoint is defined as a count of participants with treatment-emergent adverse events over 6 days, but the endpoint result and detailed event definition are not reported in the registry record. Safety entries record zero affected in the serious and other adverse-event categories, but the record does not give additional event details or uncertainty estimates. The YMRS Score is listed as a secondary outcome without a reported analysis result.

The registry records zero analyses. The statistical analysis plan, missing-data approach, analysis population, multiplicity strategy, and the study’s own sample-size justification are not reported in the registry record. The reason for termination is also unavailable. These limitations mean the registry supports a description of recorded design features and safety entries, but not a full assessment of outcome completeness, analysis choices, precision, or treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder — NCT04058249.
• Registry record last updated 2023-07-17; status last verified 2023-06.
• Results first posted 2023-07-17.
• 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

NCT04058249 is a Stanford University study titled “Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder.” It is registered as a single-group, open-label study with enrollment of 1 and status TERMINATED. The intervention is accelerated intermittent theta-burst stimulation over the right DLPFC. The primary endpoint is the number of participants with treatment-emergent adverse events over 6 days; YMRS Score is listed as a secondary outcome.

The registry records zero analyses. The primary endpoint result and the secondary outcome result are not reported in the registry record. Safety entries list 1 participant at risk and 0 affected for serious adverse events, 1 at risk and 0 affected for other adverse events, and 0 deaths. The record does not report the reason for termination, the analysis plan, or the study’s own sample-size justification. The single-group design and limited enrollment do not support a controlled estimate of treatment effect.