rTMS to Enhance Cognitive Performance and Promote Resilience: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for rTMS to Enhance Cognitive Performance and Promote Resilience (NCT04123496), a randomized na study. The primary outcome is Mean Score of Neurocognitive Performance (Fluid Cognition).

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel-group study of accelerated rTMS. The trial is marked completed, and enrollment is listed as 38. Participants were assigned among ten active dose regimens rather than to active treatment and an untreated control. The posted arm descriptions distinguish the regimens by session count: Dose 1 has 5 sessions and Dose 10 has 50, with the intervening arms increasing in session count. Each description specifies 600 pulses at 120% of resting motor threshold per session.

The designation single-masked indicates that one party was masked, but who was masked and how masking was maintained are not reported in the registry record. The randomization method, allocation concealment, treatment setting, treatment schedule over calendar days, and any stratification factors are also not reported in the registry record. The record names the Medical University of South Carolina as sponsor. It lists Cognition and Stress Reaction as conditions.

The primary outcome is a mean score of neurocognitive performance, identified as fluid cognition, with a baseline Day 1 timeframe. The outcome description refers to computerized neuropsychological tasks and a composite based on five fluid-ability measures. The registry also lists stress-resilience measures among secondary outcomes. There are 18 outcome measures in the record and 15 posted secondary outcomes. No statistical analyses are listed. In particular, the record does not report a prespecified comparison across dose groups, a follow-up timepoint for the primary endpoint, or a statistical plan for evaluating dose response. Those omissions limit what can be inferred from the posted baseline summaries.

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.

Only the first 6 of 10 groups are shown.

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Mean Score of Neurocognitive Performance (Fluid Cognition), measured over Baseline (Day 1).

The primary endpoint is the mean score for neurocognitive performance in fluid cognition, recorded at Baseline (Day 1). The record describes a composite formed from standard scores for Flanker, Dimensional Change Card Sort, Picture Sequence Memory, List Sorting, and Pattern Comparison. These tasks are intended to represent fluid abilities across cognitive domains; the wider battery description also names information-processing speed, executive function, attention, memory, working memory, inhibition, and sensorimotor function.

The score is a continuous measure, reported as a mean with a standard deviation. The description says the composite is built by averaging standard scores for the component measures and then deriving standard scores from the resulting distribution. It identifies the score as a T-score, with a general-population mean of 50 and standard deviation of 10. Higher values indicate better performance. This kind of composite can summarize performance across related tasks rather than treating any one task as the entire cognitive outcome.

For an intervention question, the central interest would usually be performance after treatment or change from baseline. The registered timeframe for this endpoint, however, is baseline, and the posted values are group means at that time. They therefore characterize starting scores, not treatment-related improvement. A post-treatment endpoint or change estimate is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

For a continuous outcome, the mean is the arithmetic average of the recorded scores in a group. It gives a measure of the group’s central location, but it does not show whether every participant had a similar score or whether scores varied widely. Here the endpoint is explicitly a mean score, and the registry also reports a standard deviation for each dose group. The mean and standard deviation together describe the observed score distribution in a compact way; neither one, by itself, estimates a treatment effect.

The posted means are specific to baseline. A randomized study may compare groups at follow-up, compare change from baseline, or use a model that adjusts follow-up scores for baseline. These approaches answer related but not identical questions. The registry record does not report which approach was planned or used for a treatment comparison. Since only baseline primary-outcome summaries are posted, there is no treatment contrast to interpret from these data.

What does the standard deviation tell the reader?

A standard deviation describes how spread out individual scores are around their group mean. A larger standard deviation indicates greater observed variability in that group; a smaller one indicates scores were more tightly clustered. It is not the same as a confidence interval. A confidence interval describes uncertainty around an estimated quantity, such as a mean or treatment contrast, under a statistical model. Confidence intervals for the group means and for between-dose effects are not reported in the registry record.

Small group counts make descriptive summaries particularly sensitive to the scores of individual participants. The posted group counts are 3 or 4, so the group means and standard deviations should not be treated as highly precise characterizations of a broader population. This is a general statistical caution about summaries from small groups, not a claim about any unreported participant-level data. The record does not provide individual observations or an uncertainty analysis that would show how stable these estimates are.

How should comparisons among doses be framed?

Because the arms received active regimens, an analysis could in principle compare outcomes across dose levels. A suitable analysis would need to define the outcome timepoint, the comparison or dose-response model, and the handling of baseline scores. The registry does not report a model, a planned contrast, or a test for a trend across session counts. It would not be valid to infer a dose-response relationship merely by looking at the order of the baseline means. Randomization is intended to support comparisons of assigned groups, but it does not make differences in baseline summaries into effects caused by treatment.

With more than two arms, the choice of comparison matters. Comparing each regimen with a selected reference dose differs from testing an overall pattern across all doses. Multiple pairwise tests also raise a general multiplicity issue: when many hypotheses are examined, the chance of at least one apparently unusual result can increase unless the analysis accounts for the testing strategy. No such testing strategy or multiplicity adjustment is reported in the registry record. Since no analyses are listed, no p-values or adjusted comparisons are available to interpret.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. For a continuous outcome, an analysis that understates variability can produce confidence intervals that are too narrow and tests that appear more decisive than warranted. The registry reports group standard deviations, but it does not report a model, residual diagnostics, or an assessment of whether a variance assumption was appropriate. There is not enough information to determine whether over-dispersion was relevant to any analysis in this study. The concept is a general reason to examine model assumptions, not a finding about this trial.

What can planning calculations add?

Sample-size calculations based on an observed effect can illustrate how many participants per arm a future study might require under stated assumptions. They are planning illustrations, not observed power and not evidence that the current study had a particular probability of detecting an effect. The calculation description for this record specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect defined as a fraction of the observed effect. It also distinguishes participants per arm for ordinary outcomes from total events for time-to-event outcomes. No valid two-arm recalculation is available for this continuous endpoint because the required comparison values are missing or not estimable. Sample-size illustrations therefore cannot supply a treatment result or replace the unreported analysis.

In general, uncertainty is best conveyed with an estimate and an interval, alongside a clearly described analysis. For this trial, the registry’s baseline means and standard deviations support descriptive reading only. The treatment-effect estimate, its confidence interval, the model, and the inferential results are not reported in the registry record.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Dose 1", "Dose 2", "Dose 3", "Dose 4", "Dose 5", "Dose 6")
n   <- c(4, 4, 4, 4, 4, 4)
m   <- c(63.5, 50.25, 59.75, 57.25, 60.5, 65.25)
sp  <- c(5.447, 10.079, 13.598, 13.15, 12.819, 5.795)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Dose 1  4  63.500  5.447  54.833  72.167
CARM  Dose 2  4  50.250  10.079  34.212  66.288
CARM  Dose 3  4  59.750  13.598  38.113  81.387
CARM  Dose 4  4  57.250  13.150  36.325  78.175
CARM  Dose 5  4  60.500  12.819  40.102  80.898
CARM  Dose 6  4  65.250  5.795  56.029  74.471

11. Multiplicity, Missing Data and Analysis Populations

The record lists 18 outcome measures and 15 posted secondary outcomes. It does not explain how the outcomes were prioritized beyond identifying the primary endpoint, whether all outcomes were assessed at the same timepoints, or how the risk of multiple testing was addressed. A multiplicity plan is important when many outcomes or dose comparisons are examined: without one, isolated findings can be difficult to distinguish from chance variation. No adjustment method, hierarchy of tests, or confirmatory analysis plan is reported in the registry record.

The registry lists zero analyses. It does not report whether the primary endpoint was analyzed as a follow-up score, a change score, or through another model. A prespecified analysis plan, outcome-specific p-values, confidence intervals, and adjusted estimates are not reported in the registry record. The record also does not state whether any interim analyses occurred.

Group counts for the posted primary outcome are 3 or 4, while enrollment is listed as 38. The reason for the difference is not reported in the registry record. Missing outcome values, withdrawals, exclusions, and the flow of participants through analysis are not described. It is therefore not possible to determine from this record whether every randomized participant contributed to each outcome or how missing observations were handled.

The analysis population is not reported in the registry record. In particular, the record does not state whether analyses followed assigned groups, included only participants who completed treatment, or used another definition. Nor does it describe imputation or sensitivity analyses for missing data. These omissions leave uncertainty about which participants and observations underlie the summaries and whether the posted groups represent all randomized participants.

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 reports adverse-event counts separately for each of the ten dose groups. For every group, the number at risk for serious adverse events matches that group’s posted count of 3 or 4. The serious-adverse-event count is 0 in every group. The record also reports 0 other adverse events in each group and 0 deaths in each group. No serious-event terms are listed.

These entries describe what was reported in the registry, not proof that an event could not occur or that the intervention has no safety risks. The number of participants represented in each arm is small, and zero reported events in these groups cannot establish the absence of uncommon events. The registry record does not provide event narratives, severity or relatedness assessments, observation duration, or details of how events were collected. It also does not explain whether the adverse-event observation period covered the same timeframe for every dose regimen.

Counts should therefore be read as a limited description of events recorded among the stated at-risk groups. They do not provide a precise comparative safety estimate across doses, particularly without uncertainty intervals or a reported analysis. Differences in exposure duration across regimens may also matter to interpretation, but the record does not report the event-monitoring schedule needed to assess that issue.

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

The posted result establishes that the registry contains baseline fluid-cognition means and standard deviations for ten active rTMS dose groups. The means vary across groups, and the outcome description says higher scores indicate better performance. The record also reports zero serious adverse events, zero other adverse events, and zero deaths in each listed dose group. These are descriptive findings about the entries recorded for this study.

The baseline scores do not show whether cognitive performance improved after stimulation. They do not establish that any dose was more effective than another, that the number of sessions was associated with a treatment response, or that treatment caused a change. Those conclusions would require post-treatment or change data and an analysis designed to compare the randomized groups. Such results are not reported in the registry record.

The scale description gives a general-population T-score mean of 50 and standard deviation of 10, but this reference does not replace a trial control group or a test of treatment effect. The trial’s arms are all described as active. There is no inactive comparator in the arm descriptions, and no primary dose contrast is reported. The study’s stated objective concerns cognitive performance and resilience, but the posted primary endpoint is baseline cognition; it cannot answer the broader objective by itself.

The safety entries likewise do not demonstrate that risks are absent. They indicate that no adverse events were entered for these groups in the reported categories. With small arm counts and no details of follow-up or event ascertainment, the record cannot establish the frequency of uncommon or later events or support a precise safety comparison.

Overall, the registry provides a limited descriptive snapshot rather than an inferential evaluation of treatment efficacy or dose selection. The statistical analysis, uncertainty around treatment effects, handling of missing observations, and analysis population are not reported in the registry record. Interpretation should remain within those boundaries.

14. Why This Trial Matters Statistically

This study is statistically notable for comparing ten active dose regimens rather than contrasting a treatment with an inactive control. The session counts span 5 to 50, while the stimulation intensity and pulses per session are specified in the arm descriptions. This design raises a dose-comparison question: whether cognitive or resilience outcomes differ across regimens with differing session counts. Answering that question requires a clearly defined outcome timepoint and a planned approach to comparing multiple groups.

The primary outcome is a composite cognitive score, which can represent performance across several tasks rather than relying on a single measure. Composite outcomes can be useful when the scientific target spans related abilities, but their interpretation depends on a transparent construction method and a timepoint relevant to the intervention question. The record describes how the composite is formed, yet lists the primary timeframe as baseline. This mismatch between a treatment-improvement aim and a baseline-only posted primary outcome is central to statistical interpretation.

The reported arm counts are small, and the registry does not give uncertainty intervals or an analysis of differences among doses. This highlights why descriptive ordering of means is not a substitute for estimation and inference. With multiple arms and multiple outcomes, the chosen contrasts and multiplicity approach can materially shape the conclusions; neither is reported in the registry record.

The record also illustrates a distinction between trial registration and a full results analysis. It contains useful design and outcome definitions, along with posted group summaries and safety counts, but does not report the statistical plan, missing-data methods, or treatment-effect analyses. For readers evaluating evidence, those omissions define what can be learned statistically: the baseline distributions can be described, but a dose-response conclusion cannot be drawn from these entries alone.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The chief trial-specific limitation for interpreting the primary outcome is its registered timeframe: Baseline (Day 1). Although the study’s stated aim concerns improving cognition, the posted primary scores do not represent change after treatment. No follow-up primary scores, change estimates, or comparisons among doses are reported in the registry record.

The arm sizes in the posted outcome summaries are 3 or 4. These small groups make the means and standard deviations descriptive, with limited precision. Enrollment is listed as 38, but the reason that the posted group counts differ from enrollment is not reported in the registry record. Participant flow, exclusions, withdrawals, and missing outcome values are not described.

All ten described regimens are active. There is no inactive control arm in the posted descriptions, and no single prespecified comparator is identified. The record does not state how the doses were randomized, who was masked, or how masking was maintained. It also does not report the schedule of outcome assessments after baseline or the duration of follow-up.

The statistical methods needed to assess dose effects are not reported in the registry record. This includes the analysis model, covariate adjustment, planned contrasts, multiplicity handling, analysis population, and methods for missing data. No analyses are listed, and no confidence intervals or p-values for treatment comparisons are reported. The secondary-outcome entries are not accompanied by posted analyses in this record.

Safety information is limited to group counts of serious events, other events, and deaths. The registry does not describe event definitions, collection procedures, relatedness judgments, or observation windows. Zero recorded events in small groups should not be read as proof that no risk exists. These limitations prevent a robust conclusion about efficacy, dose selection, or comparative safety from the registry entries alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: rTMS to Enhance Cognitive Performance and Promote Resilience — NCT04123496.
• Registry record last updated 2025-10-16; status last verified 2025-09.
• Results first posted 2025-10-16.
• 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

The registry describes a completed randomized, single-masked, parallel-group study sponsored by the Medical University of South Carolina, with enrollment listed as 38. The study title concerns rTMS to enhance cognitive performance and promote resilience in astronauts. Ten active accelerated rTMS regimens vary in session count from 5 to 50; the descriptions specify 600 pulses per session at 120% of resting motor threshold.

The primary outcome is mean fluid-cognition performance at Baseline (Day 1), reported as a continuous score with a standard deviation. The posted group counts are 3 or 4. The registry lists 18 outcome measures and 15 posted secondary outcomes, but no analyses. It reports 0 serious adverse events, 0 other adverse events, and 0 deaths in each dose group.

Because the primary values are baseline summaries and treatment-effect analyses are not reported in the registry record, the posted results do not establish improvement or a difference among doses. Missing-data methods, the analysis population, multiplicity procedures, and uncertainty estimates are also not reported.