The Effect of Brain Anatomy on the Efficacy of Brain Stimulation Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Brain Anatomy on the Efficacy of Brain Stimulation Therapy (NCT04586387), a randomized na study. The primary outcome is Change in Corticomotor Excitability With Active Stimulation on Bicep Muscle.

2. Clinical Question

3. Trial Design

This was a randomized, unmasked crossover study sponsored by Virginia Commonwealth University. The registry lists the study as completed, with an enrollment of 12. The study began on 2020-11-09 and its primary completion date is listed as 2022-07-08. The phase is recorded as NA. These administrative details describe the study record, not the results of the primary outcome.

In a crossover design, participants receive or undergo more than one study condition in a planned order, so comparisons can be made within participants as well as between assigned sequences. Here, the registry describes two possible orders for stimulation over the bicep and finger (FDI) muscles. Both intervention descriptions specify sham stimulation followed by active stimulation. The record states that the two muscle groups were studied in separate sessions and that there was a 3 day rest period between them.

Randomization refers to assignment to a sequence by chance; it does not by itself show that groups were comparable in every respect or that the outcome analysis was unbiased. Masking is listed as none. The registry therefore does not describe participants or study personnel as masked to the assigned condition. Further details about who knew the sequence, how randomization was generated or concealed, and how stimulation order was implemented are not reported in the registry record.

The primary outcome timeframe is approximately 7 days, while the intervention descriptions refer to two sessions and a rest period between muscle groups. The record does not provide more detailed timing for outcome measurement or explain how the timeframe relates to each session. Although four outcome measures are listed, the registry reports no analyses. A detailed protocol, sample-size justification, or statistical analysis plan is 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.

Before assignment: Total enrollment was 12 with all participants receiving both interventions

Overall Study

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

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 Corticomotor Excitability With Active Stimulation on Bicep Muscle, measured over approximately 7 days.

The primary endpoint is titled “Change in Corticomotor Excitability With Active Stimulation on Bicep Muscle.” It is a continuous measure, described as a mean, with the unit reported as percentage of Mwave. The record says that the amplitude of motor evoked potentials (MEPS) will be used to determine the level of corticomotor excitability. The stated timeframe is approximately 7 days, and the outcome population is described as nonimpaired.

In general, motor evoked potentials are responses elicited by stimulation of the motor system. Their amplitude can be used as an indicator of corticomotor excitability. A continuous endpoint retains the measured magnitude rather than reducing the observation to a simple yes-or-no category. A mean describes the average measured value in a group or condition; a standard deviation describes how dispersed individual values are around that mean.

The registry identifies the endpoint and its intended measurement, but does not report the observed mean, standard deviation, change, or comparison between conditions. It also does not give enough detail to specify the exact calculation used to define change, the measurement schedule, or the handling of repeated measurements. The endpoint description therefore explains what the investigators intended to assess, not the magnitude or direction of any observed effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized crossover design and a continuous primary outcome summarized as a mean with standard deviation. It does not include an analysis plan or any outcome analyses. The explanations below describe general statistical ideas relevant to these design features; they do not establish which methods the investigators actually used.

What does randomization contribute?

In general, randomization assigns participants to planned study sequences using chance. It helps prevent systematic selection of a sequence based on known or unknown participant characteristics. It does not guarantee that the sequences will be identical in a small study, and it does not address bias caused by missing data, measurement, deviations from the assigned sequence, or unmasked assessment. The record says allocation was randomized, but the method for generating or concealing assignment is not reported in the registry record.

How does a crossover comparison differ?

In a crossover study, a participant experiences more than one condition, often in a designated order. Because measurements from one person tend to be related, a statistical analysis generally needs to account for within-participant dependence. This can make a within-participant comparison more informative than comparing unrelated groups, provided the design and analysis assumptions are appropriate. The record describes two sequences and a 3 day rest period between the muscle groups. It does not identify an analysis model or report whether sequence and period effects were evaluated.

Carryover is a general concern when an effect of an earlier condition could persist into a later condition. A rest period may be part of a design intended to separate conditions, but its presence alone does not demonstrate that carryover is absent. Whether carryover was assessed, and how it was handled if present, is not reported in the registry record. The record also does not give enough detail to determine how the sham and active phases within each session entered the primary analysis.

What do mean and standard deviation describe?

For a continuous outcome, the mean is the arithmetic average of measurements. The standard deviation describes the spread of individual observations around that average. The two quantities answer different questions: the mean indicates the average level, while the standard deviation describes variability among observations. Neither quantity, by itself, shows how precisely a treatment contrast has been estimated. The registry names the mean and standard deviation as the outcome summary, but posts no values for the primary endpoint.

What would an effect estimate and confidence interval add?

In general, an effect estimate gives the observed size and direction of a difference or change. A confidence interval communicates uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates more precision than a wide interval, but precision does not establish clinical importance. A confidence interval should be interpreted alongside the outcome definition, study design, and potential sources of bias. No primary effect estimate or confidence interval is reported in the registry record.

How should a significance test be read?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, nor does it describe the size or importance of an effect. A test result also depends on the chosen model and analysis plan. The registry lists no analyses and does not report a p-value or a prespecified significance threshold for the primary outcome. The statistical plan, including any interim analyses, is not reported in the registry record.

What can sample-size planning show?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, power, allocation, and analysis method. It is not a result observed in participants and cannot establish that a study was adequately powered after the fact. The registry lists enrollment of 12, but a trial-specific sample-size justification is not reported in the registry record. The record does not report the assumptions used to choose that enrollment or an observed outcome effect from which to judge the precision of the study.

The methods information needed to reproduce or evaluate the primary analysis—including the model, estimand, handling of repeated measurements, covariates, missing observations, and analysis population—is not reported in the registry record. As a result, statistical concepts can clarify what the design would generally require, but the record does not permit assessment of whether a particular method was used or whether its assumptions were met.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, but does not report analyses for them. When a study examines multiple outcomes, timepoints, or comparisons, multiplicity can increase the chance of obtaining at least one apparently notable result by chance. In general, investigators may address this by prespecifying a primary comparison, adjusting inference, or clearly distinguishing confirmatory analyses from exploratory ones. The registry identifies a primary outcome title, but a multiplicity strategy is not reported in the registry record.

The record does not describe missing-data handling. It does not report the number of participants with primary outcome measurements, the number of missing observations, reasons for missingness, or any imputation or sensitivity analysis. In general, missing-data methods rely on assumptions about why measurements are absent; different assumptions can lead to different estimates. Without participant flow and analysis details, the completeness and potential impact of missing data cannot be evaluated.

The analysis population is also not specified in the registry record. It is not clear whether the intended analysis included everyone randomized, only participants who completed both conditions, or another defined group. In a crossover study, incomplete participation in one condition can affect which within-participant comparisons are available. The registry record does not say how such cases would be included.

No interim analyses, stopping rules, or detailed statistical analysis plan are reported in the registry record. The absence of these details in the registry does not establish that no such plans existed; it means their use cannot be assessed from this record. Since no analyses or primary outcome results are posted, multiplicity, missingness, and analysis-population choices cannot be checked against reported estimates.

11. 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 lists one safety group titled Brain Stimulation. It records 12 participants at risk for serious adverse events and 0 participants affected. It also records 12 participants at risk for other adverse events and 0 affected, with 0 deaths. No serious adverse event terms are listed.

These figures describe what is recorded in the registry, not a guarantee that no adverse experiences occurred. The record does not provide event-level descriptions, severity categories beyond the serious/other distinction, timing, relatedness assessments, or a narrative about safety monitoring. It also does not provide enough detail to determine the duration or completeness of safety follow-up for each participant. The listed group counts should therefore be read as reported safety entries, not as a complete account of every possible event.

In general, a count of zero in a study of limited enrollment is not proof that an event cannot occur. It describes the observed and reported count in the record. These figures do not establish that the intervention is safe or unsafe, and they do not support comparisons with another treatment because no such safety comparison is reported.

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

The registry record describes a randomized, unmasked crossover study intended to examine whether brain anatomy affects the efficacy of brain stimulation therapy. It gives a primary outcome focused on change in corticomotor excitability during active stimulation over the bicep muscle, using motor evoked potential amplitude as the measure. It also describes stimulation over a finger muscle and two orders of the muscle-group sessions.

What the posted record does not provide is the primary outcome result. There is no reported mean change, standard deviation, comparison estimate, confidence interval, or statistical test. Therefore, the registry record does not show whether the measured outcome increased, decreased, or differed between conditions, and it does not show how precise any such difference was. The study's stated question should not be mistaken for a finding.

The design features can help readers understand how the study was organized, but they do not replace outcome data. Randomization concerns assignment; crossover concerns the planned sequence of conditions; and the rest period is a design feature. None establishes that the intervention changed the endpoint or that a comparison was unbiased. The study is listed as unmasked, and the registry does not report enough procedural or analysis detail to assess other potential sources of bias.

The listed enrollment and safety figures also have a limited interpretation. Enrollment of 12 does not establish how many participants contributed to the primary analysis, and the registry does not provide a participant flow or analysis population. The recorded zero counts for adverse events and deaths are registry entries, not proof of absence of all harms.

The most defensible conclusion is about reporting: the record documents the study design, intended endpoint, enrollment, and recorded safety counts, but does not report primary efficacy analyses. No conclusion about the size, direction, precision, or practical importance of an effect can be drawn from the registry record alone.

13. Why This Trial Matters Statistically

This study is statistically notable because its question concerns whether anatomy may relate to response to a brain stimulation technique, while its design includes stimulation over two muscle locations in a randomized crossover arrangement. Such questions make the definition of the comparison important: an interpretation depends on which conditions are contrasted, when measurements are taken, and how repeated observations from the same participant are handled.

The crossover structure highlights a general strength and a general analytic requirement. Repeated measurements within a participant can support direct within-person comparisons, reducing the influence of characteristics that remain stable during the study. At the same time, measurements within a person are not independent. Period, sequence, and carryover may also matter in general. The registry describes the sequences and a 3 day rest period, but does not report the analysis used to address these considerations.

The record also illustrates the distinction between a clearly stated research question and an interpretable statistical result. It identifies a continuous primary endpoint and its intended measurement, yet posts no analysis results. Without an effect estimate and uncertainty, readers cannot distinguish a potentially meaningful effect from a small or imprecisely measured one. Enrollment alone cannot supply that missing information.

Finally, the lack of reported analysis and missing-data details limits reproducibility. Clear reporting of the analysis population, outcome calculation, within-participant model, multiplicity handling, and missing observations would help readers understand how the planned question was translated into an estimate. Their absence from the registry record does not reveal what analyses may have been conducted elsewhere; it limits what can be concluded from this record.

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 central limitation for interpretation is that the registry record contains no analysis results for the primary endpoint. It does not report the observed mean change, standard deviation, effect estimate, confidence interval, or test result. The record lists four outcome measures but no analyses. Accordingly, the size, direction, and precision of any primary outcome difference cannot be assessed.

Important design and conduct details are also not reported in the registry record. These include participant eligibility criteria beyond the description as healthy and nonimpaired, participant characteristics, the randomization method, allocation concealment, the exact measurement schedule, and the implementation of sham and active stimulation. The record describes no masking, but does not clarify which roles were aware of treatment or sequence.

For a crossover study, interpretation may depend on how within-participant measurements, session order, period effects, and possible carryover are handled. The record notes a 3 day rest period but does not report whether carryover was assessed or how it would affect analysis. It does not report the statistical model or analysis population. The number of participants who completed each session or contributed outcome data is also not reported in the registry record.

The registry does not report a sample-size justification, missing-data approach, multiplicity strategy, or detailed statistical analysis plan. The posted safety counts do not include event descriptions or follow-up detail. These limitations concern the information available in the registry record; they do not establish that the study lacked additional documentation or analyses outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Brain Anatomy on the Efficacy of Brain Stimulation Therapy — NCT04586387.
• Registry record last updated 2024-05-03; status last verified 2024-05.
• Results first posted 2023-12-18.
• 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.

18. Record Summary

This completed study, sponsored by Virginia Commonwealth University, was randomized, unmasked, and used a crossover design. The registry lists enrollment of 12 healthy participants and describes intermittent theta burst stimulation over the bicep and finger (FDI) muscles, with sham followed by active stimulation and a 3 day rest period between muscle groups.

The primary outcome was change in corticomotor excitability during active stimulation over the bicep muscle, measured using motor evoked potential amplitude as a percentage of Mwave. The timeframe was approximately 7 days. The registry lists four outcome measures but no analyses and reports no primary endpoint result. Safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths. These data describe the registry entries; they do not establish efficacy or provide a complete assessment of safety.