This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Establishing Functional Biomarkers for Spaced Theta-Burst Stimulation (NCT03687892), a randomized na study. The primary outcome is Changes in Motor Evoked Potential.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03687892 |
| Phase | NA |
| Condition | Healthy Volunteers |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 37 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Stanford University |
| Results posted | Yes |
2. Clinical Question
Population
The registry record identifies healthy volunteers as the study population. Its brief summary says the investigators planned to use fMRI methods in 10 healthy participants. The enrollment field, however, lists 37. The record does not explain the difference between the planned number in the summary and the enrollment figure.
Intervention
The study examined continuous theta-burst stimulation (cTBS) and intermittent theta-burst stimulation (iTBS), forms of repetitive transcranial magnetic stimulation. The intervention descriptions specify two applications of 40s at 80% resting motor threshold for each form, with a 15 minute intersession interval. Stimulation was directed to the left motor cortex; further detail on how the location was determined is not reported in the registry record.
Comparator
The record identifies both stimulation forms and describes the study as randomized and crossover. It does not provide a separate untreated, sham, or usual-care comparator in the listed interventions. The exact sequence of conditions, and whether every participant received both forms, are not reported in the registry record.
Primary question
The primary outcome was change in motor evoked potential, a measure of motor-system response. The study description asks how long the effects of spaced cTBS and iTBS on that response last. The registry specifies assessment prior to and immediately after TBS sessions on each day, with sessions separated by 3+ days. No post-baseline data were collected for this outcome, so the registry record contains no result answering the primary question.
The broader research aim was to assess changes in brain activity and blood flow during tasks and at rest, alongside motor responses and pain perception. Listed secondary outcomes include resting-state functional connectivity, motor cortex activity assessed by the BOLD signal, and arterial perfusion. These aims describe what the investigators planned to assess, not results. The registry record does not provide analyzed outcome values for those measures.
3. Trial Design
NCT03687892 is listed as a randomized, single-masked, crossover study sponsored by Stanford University. Its phase is recorded as NA, and its condition is healthy volunteers. The study status is terminated. The registry record gives a start date of 2019-04-01 and a primary completion date of 2022-10-22. Enrollment is listed as 37, while the brief summary describes a plan to use fMRI methods in 10 healthy participants. The reason for this difference is not reported in the registry record.
The two listed interventions are continuous theta-burst stimulation and intermittent theta-burst stimulation. Each intervention description specifies two applications of 40s at 80% resting motor threshold, with a 15 minute intersession interval. Both are described as directed to the left motor cortex. The descriptions do not give enough detail to establish the order in which participants received conditions or the full procedure for locating the stimulation site.
In general, a crossover design assesses participants under more than one condition, allowing comparisons that can account for stable differences between individuals. That design can be informative when the outcome is measured repeatedly, but interpretation may depend on condition order, the time between conditions, and whether effects persist into a later period. The registry record does not report the sequence allocation, a washout plan, or analyses for order or carryover effects. The primary outcome timeframe notes sessions on each day separated by 3+ days, but does not describe all study visits or establish whether that interval was intended as a washout.
Single masking indicates that some masking was used, but the identity of the masked group is not reported in the registry record. The record identifies randomization but does not describe how the allocation sequence was generated or concealed. These omissions limit assessment of how the study was implemented; they do not establish that any particular design feature was or was not used.
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
| Stage | All Participants |
|---|---|
| STARTED | 37 |
| COMPLETED | 0 |
| NOT COMPLETED | 37 |
Analysis population for the primary outcome, as defined in the registry: No outcome measure analysis was possible because no post-baseline data were collected.
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.
Population: Participants who were consented and received baseline scan.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 22 | |
| Age, Continuous | years | 41.77 (SD 12.99) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 5 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United States | Participants | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Motor Evoked Potential, measured over Prior to and and immediately after TBS sessions on each day (separated by 3+ days).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in motor evoked potential. A motor evoked potential is a measurable response of the motor system following stimulation; the registry uses it to assess the duration of the effect of spaced cTBS and iTBS. In general, an outcome measured before and after an intervention can describe whether the observed response changes over the specified assessment period. Repeated measurements may also help characterize how a response evolves over time, if the necessary observations are collected and reported.
The registry specifies measurement prior to and immediately after TBS sessions on each day, with sessions separated by 3+ days. That timeframe identifies the planned assessment context, but it does not provide a numerical definition of the endpoint, a unit, or a summary measure. Those details are not reported in the registry record. The outcome field states that no outcome measure analysis was possible because no post-baseline data were collected. Consequently, there is no posted primary endpoint estimate, measure of precision, or statistical test to interpret.
The choice of motor evoked potential is consistent with the stated aim of assessing motor-system response to stimulation. The record also describes broader aims involving fMRI, motor responses, and pain perception. Those aims do not substitute for observed endpoint data. Without post-baseline measurements, the registry cannot establish the size, direction, variability, or duration of a change in motor evoked potential.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the registry record reports no post-baseline data for the primary outcome. It explicitly states that no outcome measure analysis was possible. Accordingly, there is no primary outcome estimate to interpret: no reported change in motor evoked potential, no confidence interval, and no test of statistical significance. This is an absence of analyzed outcome data, not evidence that the measured response was unchanged.
The study was intended to examine effects of cTBS and iTBS on brain and behavioral measures. The registry lists four outcome measures in total: the primary motor evoked potential outcome and three secondary outcomes concerning resting-state functional connectivity, motor cortex activity assessed by the BOLD signal, and arterial perfusion. The record does not provide numeric results for these measures. It also reports zero analyses. Thus, the listed aims and outcome names should be read as descriptions of the study's intended assessments, not as findings.
The randomized crossover design could, in general, support comparisons between conditions within participants. Such comparisons depend on how conditions were sequenced and how repeated measurements were analyzed. The record does not report the sequence, an analysis plan, or results that would show how the design was used. The design label alone cannot establish the effectiveness of a comparison or remove concerns about period and carryover effects.
Enrollment is listed as 37, while the brief summary describes a plan involving 10 healthy participants. These are different registry entries, and the record does not reconcile them. Neither number indicates how many participants contributed usable data to a particular outcome. The primary outcome field says no post-baseline data were collected; participant counts for other outcome analyses are not reported in the registry record.
The safety fields list 37 participants at risk for serious adverse events and 0 affected, 37 at risk for other adverse events and 0 affected, and 0 deaths. These figures describe the registry's event reporting. They do not provide details about the method of surveillance, the length of observation, or whether every type of event was captured. They should not be interpreted as an estimate of the probability of harm in other settings.
Overall, the posted record allows readers to identify the study question, design labels, interventions, and reporting gaps. It does not permit a statistical conclusion about whether either stimulation condition changed the primary outcome or the secondary measures. No treatment effect should be inferred from the stated aims, the design, or the lack of posted outcome data.
9. Statistical Methods Explained
The registry identifies the study as randomized, single-masked, and crossover. Those labels describe aspects of the design, but the record does not give a statistical analysis plan. In particular, it does not report the planned model, the primary contrast, the treatment of repeated observations, or the handling of missing measurements. The points below explain general statistical concepts relevant to this design; they are not claims about analyses performed in this study.
What randomization can contribute
In general, random allocation can reduce systematic differences between groups or condition sequences at the start of a study. Its value depends on how allocation is implemented and maintained. The registry says the study was randomized, but the method used to generate or conceal allocation is not reported in the registry record. Randomization by itself does not show that groups or sequences were balanced, and it does not replace reporting the outcome analysis.
What a crossover design compares
In general, a crossover study measures participants under multiple conditions and can compare their responses across those conditions. Because the same person contributes observations under more than one condition, a suitable analysis may account for within-person dependence. Measurements from the same participant are generally not independent in the way measurements from different participants may be treated in a simple between-group comparison. The analysis should reflect that structure, but the model used is not reported in the registry record.
Crossover interpretation may also depend on condition order, changes over time, and persistence of effects from an earlier condition. A washout interval may be relevant when an effect could continue into a later condition. The registry gives a primary outcome timeframe that notes sessions separated by 3+ days and intervention descriptions that specify a 15 minute interval between two applications. These descriptions refer to different timing details; the record does not explain a complete period structure or identify an intended washout. It also does not report analyses of order or carryover.
How to read estimates and uncertainty
In general, an effect estimate describes the size and direction of a comparison on the outcome scale. A confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method. A narrow interval is more precise than a wide interval, while an interval that includes values consistent with little or no difference may leave substantial uncertainty about the effect. A p-value, when reported, summarizes how compatible the observed data are with a specified null model; it does not measure the size or clinical importance of an effect.
None of these primary outcome statistics is reported in the registry record. No change estimate, standard error, confidence interval, or p-value is available for motor evoked potential. The registry states that no post-baseline data were collected for the primary outcome, so the missing analysis cannot be reconstructed from the information recorded there.
What the outcome list means
The record identifies one primary outcome and three secondary outcomes, for four measures in total. In general, multiple outcomes create more than one opportunity to observe a nominally unusual result. A prespecified hierarchy or an adjustment for multiple testing can help define how results should be interpreted across outcomes. The registry record does not report whether multiplicity was addressed, nor does it provide results for the secondary outcomes. It is therefore not possible to assess a pattern of findings across endpoints.
Planning calculations and observed evidence
In general, a sample-size calculation uses assumptions about an effect, variability, significance level, and desired power to plan recruitment. A planning illustration based on an observed effect is not the same as a prospective design justification and cannot replace an analysis of observed data. The registry record describes planning-illustration assumptions, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the target effect is expressed as a fraction of the observed effect. However, no numerical planning outputs are included in the record summarized by these registry entries. The trial's own sample-size justification is not reported in the registry record. Any planning illustration should be understood as planning context, not observed power or evidence of an outcome effect.
In general, over-dispersion occurs when the variability in data is greater than a model expects. If present, it can make standard errors too small and confidence intervals too narrow under an inadequately specified model. The registry does not report enough outcome data or model details to assess distributional assumptions, variability, or over-dispersion for this study. No claim about those features can be made from the listed design and outcome titles alone.
10. Multiplicity, Missing Data and Analysis Populations
The record lists one primary outcome, changes in motor evoked potential, and three secondary outcomes: resting-state functional connectivity between the M1 Hotspot and other motor areas, motor cortex activity assessed by the BOLD signal, and arterial perfusion. The primary outcome field states that no outcome measure analysis was possible because no post-baseline data were collected. The registry record does not provide numerical results for the secondary outcomes either.
When a study assesses several outcomes, general statistical practice distinguishes the primary question from additional questions and specifies how inference across them will be handled. If each outcome is tested independently at a conventional threshold, the chance of at least one false-positive result can increase. A prespecified hierarchy, adjustment, or clearly exploratory interpretation can address this issue. Whether any such approach was planned or used is not reported in the registry record. With no posted outcome analyses, there are no reported tests to evaluate for multiplicity.
The record does not describe a missing-data strategy, a method for handling incomplete repeated measures, or an analysis population. It does not state how many participants had usable data for each endpoint. The enrollment field lists 37, but that count cannot be assumed to be the analysis population. The primary outcome field specifically reports no post-baseline data collection, which prevents its analysis; the record does not explain why those data were absent or whether the same situation applied to secondary outcomes.
In general, conclusions can depend on whether analyses include all randomized participants, only participants with observed outcomes, or another defined group. The registry does not identify which population was intended for analysis. It also does not report interim analyses or stopping rules. These omissions leave the statistical handling of multiplicity and missingness unresolved and prevent readers from assessing how those choices might affect estimates.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Participants | 0 | 37 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Participants | 0 of 37 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Participants | 0 of 37 |
The registry lists 37 participants at risk for serious adverse events, with 0 affected. It also lists 37 at risk for other adverse events, with 0 affected, and reports 0 deaths. These are the posted event counts for the groups described in the record. No serious adverse-event terms are listed.
In general, an at-risk count identifies the number of participants included in a particular safety summary. A count of zero affected means that no events in that category were reported for the listed group in the registry record. It does not establish that an event is impossible, and it does not by itself quantify risk beyond the participants and observation represented by the report. These counts should be read as descriptive safety reporting, not as a comparison between stimulation conditions.
The record does not report the length or completeness of safety follow-up, definitions used for event categories, or a breakdown by intervention or study period. It also does not describe how events were elicited or adjudicated. Without those details, the zero counts cannot establish that no unreported events occurred or support a broader safety conclusion. The figures do not provide evidence about the primary motor evoked potential outcome, which had no post-baseline data.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, single-masked crossover study of cTBS and iTBS in healthy volunteers was registered, and that it is listed as terminated. It describes intended assessments of motor evoked potential, functional connectivity, BOLD signal activity, and arterial perfusion. It also records an enrollment of 37 and safety counts with 0 serious adverse events, 0 other adverse events, and 0 deaths.
The record does not report an analyzed primary outcome. It states that no post-baseline data were collected for motor evoked potential, so there is no estimate of how that measure changed after either stimulation condition. The record also has zero listed analyses and provides no numerical findings for the secondary outcomes. Therefore, it cannot establish whether a measured response changed, how large any change was, how precise an estimate might be, or how long a change lasted.
This absence of outcome evidence is not evidence that the interventions had no effect. It also is not evidence that they had an effect. The registry record does not support a conclusion in either direction. Study aims, intervention descriptions, enrollment, and design labels cannot stand in for analyzed outcome data.
In general, a clinical or research result is interpreted using observed outcomes, an appropriate comparison, and an account of uncertainty and analysis choices. The registry does not provide those elements for the primary question. Its description can inform readers about what was intended and what was recorded, while leaving the efficacy and duration questions unanswered. The safety counts are likewise limited to the posted event summary and do not establish safety beyond that record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a research question and an answer supported by outcome data. The registry gives a clear primary question—whether spaced cTBS and iTBS are followed by changes in motor evoked potential and how long those changes last—but also states that no post-baseline data were collected for that outcome. Without those observations, the intended comparison cannot be estimated.
The design labels also show why statistical interpretation requires more than knowing that a study was randomized and crossover. In general, crossover data may allow within-person comparisons, but interpreting them requires information about condition order, repeated measurements, timing, and the model used. Those details are not reported in the registry record. The design alone does not tell readers how an estimate would have been produced or how uncertainty would have been quantified.
The record further distinguishes planned scope from analyzed evidence. It names four outcome measures and describes fMRI and behavioral aims, but reports zero analyses. The enrollment field and narrative plan also differ: enrollment is listed as 37, while the brief summary describes a plan involving 10 healthy participants. The record does not explain that difference. Such distinctions matter because a planned sample, an enrollment count, and the number contributing data to an endpoint are not interchangeable.
For biostatisticians and clinical researchers, the record underscores the importance of complete outcome reporting: participant flow, outcome availability, prespecified analyses, effect estimates, and measures of uncertainty. When those elements are absent, the appropriate statistical conclusion is limited. Here, the posted record documents the study framework and the missing primary outcome data, but it does not answer the question of whether stimulation changed the measured outcomes.
14. 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 principal limitation for interpreting this study is the lack of post-baseline data for the primary outcome. The registry explicitly says that no outcome measure analysis was possible. As a result, no estimate or uncertainty measure is available for motor evoked potential, the endpoint intended to address the duration of stimulation effects.
The registry lists three secondary outcomes but provides no numerical results for them. It reports zero analyses overall. The record therefore does not permit evaluation of the direction, size, precision, or consistency of any secondary outcome findings. It also does not explain why post-baseline primary outcome data were not collected or whether missing data affected other measures.
Important design and analysis details are not reported in the registry record. These include the exact crossover sequence, allocation procedures, identity of the masked group, full timing of study periods, any washout approach, the statistical model, the analysis population, and plans for missing data or multiplicity. The brief intervention descriptions identify stimulation settings and location but do not give a complete account of the protocol. The record also does not reconcile the enrollment figure of 37 with the brief summary's plan to use 10 healthy participants.
The safety summary is limited to event counts and does not describe follow-up duration, event ascertainment, or breakdown by condition. Finally, the study concerns healthy volunteers, as recorded; the registry provides no basis for extending its intended question or safety counts to other populations. These limitations define what can be inferred from the record and do not establish what happened outside the information it reports.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Establishing Functional Biomarkers for Spaced Theta-Burst Stimulation — NCT03687892.
- Registry record last updated 2023-11-09; status last verified 2023-10.
- Results first posted 2023-11-09.
- 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.
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18. Record Summary
NCT03687892, “Establishing Functional Biomarkers for Spaced Theta-Burst Stimulation,” is listed as a randomized, single-masked crossover study sponsored by Stanford University. The condition is healthy volunteers, the phase is NA, and the status is terminated. Enrollment is listed as 37; the brief summary describes a plan involving 10 healthy participants.
The study examined continuous and intermittent theta-burst stimulation. Its primary outcome was change in motor evoked potential, with secondary outcomes concerning resting-state functional connectivity, BOLD signal activity, and arterial perfusion. The record states that no post-baseline data were collected for the primary outcome and reports zero analyses. It provides no numerical outcome results.
The safety record lists 0 serious adverse events, 0 other adverse events, and 0 deaths among 37 participants at risk in each event category. The posted figures are descriptive and do not resolve the unanswered outcome questions.