Brain Markers of Improvements in Cognitive Functioning: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brain Markers of Improvements in Cognitive Functioning (NCT03490110), a randomized na study. The primary outcome is Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery.

2. Clinical Question

The registry describes a pilot project motivated by persistent difficulties after traumatic brain injury that can affect a person’s ability to pursue goals. It focuses on skills such as concentration, memory, staying calm, and meeting challenges. The clinical question is therefore whether a structured skill-training approach can be evaluated against usual care in this context, alongside investigation of possible brain-activity markers related to response.

The record lists traumatic brain injury, brain injuries, stress, attention deficit, and executive dysfunction among its conditions. It does not report detailed eligibility criteria, participant characteristics, or the specific clinical setting of each participant. The summary refers to Veterans, but the record does not provide enough detail to define a more precise study population from the posted information alone.

The outcome available for statistical interpretation is a composite of attention and executive-functioning test performance measured at baseline. Because the registry gives baseline means and standard deviations but does not provide an estimable two-arm continuous outcome comparison, the posted values cannot establish whether the intervention changed cognition relative to usual care. The stated interest in EEG markers is also distinct from evidence of a behavioral treatment effect; the posted information does not provide an analysis connecting EEG changes to differences in cognitive response.

3. Trial Design

The record describes a randomized, double-masked, parallel-group study. Its status is completed, and the listed enrollment is 18. The sponsor is the VA Office of Research and Development. The registry lists the phase as NA. The study start is recorded as 2017-10-01 and primary completion as 2019-03-01.

The two named interventions are State regulation skill training and Treatment-as-usual. The training arm is described as a behavioral program intended to strengthen goal-directed cognitive-emotional state regulation. The description emphasizes practice and active application across challenge contexts, with digital scenarios providing experiential learning opportunities. The available arm description ends before explaining the full scenario design, so further details are not reported in the registry record. The comparator is described as clinical care as usual in VA and other clinics.

Random allocation means the study was designed to assign participants to groups by chance, while double masking indicates that the registry classifies the trial as double-masked. The record does not specify who was masked or how masking was maintained. A parallel design means participants are assigned to one intervention group rather than crossing between interventions; further implementation details are not reported.

The posted primary endpoint is a composite score assessed at Week 1 before the intervention period. Thus, the available endpoint description identifies a baseline assessment, not a follow-up contrast. Although the trial summary describes an aim to test behavioral effects and examine EEG markers, the registry record does not report an estimable two-arm comparison for the continuous primary outcome. A more detailed protocol, treatment schedule, adherence information, and the planned statistical analysis 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 Composite Score of Attention and Executive Functioning From a Neurocognitive Test Battery, measured over Week 1, before intervention period (baseline).

The primary outcome is a composite score of attention and executive functioning from a neurocognitive test battery. The registry says the investigators combined standardized performance on measures covering letter-number sequencing, auditory consonant trigrams, digit vigilance, color-word interference, and Trail Making Test B. Individual test performance was scored using population norms, converted to standardized Z-scores, and averaged to create the composite. The stated unit is units on a scale, with the composite measure described as a Z-score.

A Z-score expresses how far a score is from the population mean in standard-deviation units. As the registry explains, zero corresponds to the population mean, while positive and negative values indicate performance above and below that mean, respectively. Combining several measures can represent broader attention and executive-function performance rather than relying on a single task. It can also provide a common scale for measures that otherwise use different scoring conventions.

The listed timeframe is Week 1, before the intervention period, so the posted primary endpoint is a baseline measure. That timing matters: baseline scores describe starting status but do not, by themselves, show change during training or a difference between groups in change. The record does not report a follow-up primary composite value or an estimable two-arm comparison for this continuous outcome. It therefore does not support a conclusion about the intervention’s effect on this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s composite score is a numerical value on a standardized scale. The registry identifies the summary parameter as a mean and the measure of dispersion as a standard deviation. A mean describes the central location of the observed scores, while a standard deviation describes their spread around that mean. These summaries are descriptive; on their own they do not test whether groups differ or quantify uncertainty in a treatment-effect estimate.

The reported means and standard deviations refer to the baseline assessment. A treatment comparison ordinarily needs an outcome aligned with the question, such as a between-group comparison at follow-up or a comparison of changes over time. The registry’s listed primary timeframe is before the intervention period, and it does not report an estimable two-arm comparison for the continuous endpoint. The posted baseline summaries therefore should not be substituted for a treatment-effect analysis.

A confidence interval, in general, gives a range of values compatible with a statistical estimate under the assumptions of the analysis. Its width conveys precision: a wider interval indicates more uncertainty than a narrower one. No confidence interval is reported for the primary comparison in the registry record. A p-value, which in general measures how unusual data would be under a specified null model, is also not reported for that comparison. Neither can be reconstructed from the information in the record without making assumptions beyond the posted results.

Standard deviations and standard errors serve different purposes. A standard deviation describes variability among individual observations; a standard error describes uncertainty in an estimated quantity, such as a mean. The endpoint lists standard deviations, not standard errors. The posted standard deviations should therefore be read as descriptions of score spread, not as confidence limits around the group means.

For continuous outcomes, assumptions about the distribution of observations and the analysis model can affect inference. A normal approximation may be used in some analyses, but the registry record does not report the primary analysis model or its assumptions. In general, small samples can make estimates and distributional assumptions particularly consequential. The registry does not provide enough information to assess whether a particular model was used, whether model assumptions were checked, or whether any adjustment was applied.

Over-dispersion is a general concern when observed variability exceeds what a model expects. It can make standard errors too small and confidence intervals too narrow if the analysis does not account for that extra variation. This concept is particularly relevant to some count outcomes, but the posted primary endpoint is continuous. The record does not report an over-dispersion assessment, nor does it identify a primary-outcome model whose adequacy could be assessed.

The registry gives an outcome sample size of 6 for each arm. These are the sample sizes attached to the posted baseline summaries, not proof that all enrolled participants contributed data or that the same analysis set was used for every outcome. The reason the outcome sample size differs from the enrollment figure is not reported in the registry record. The record also does not specify an intention-to-treat population, a per-protocol population, or rules for handling participants with unavailable measurements.

The record’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are characterized as illustrations rather than the trial’s own design calculations. In general, a sample-size illustration estimates the number of participants that would be needed under specified assumptions to detect a chosen effect with a target probability of detection. It is not observed power and does not show that the completed trial was designed or conducted to those assumptions. The record does not report a sample-size justification for the original trial design.

Planning based on an observed effect is especially uncertain in a pilot study because an effect estimate can vary substantially from one sample to another. In general, using a fraction of an observed effect to examine alternative planning scenarios can show how required sample size responds to the assumed target effect. Such calculations remain hypothetical: they do not turn baseline summaries into a treatment-effect estimate, and they do not establish the true effect. The registry record does not report the statistical method used to calculate the primary outcome comparison, and the posted comparison is not estimable.

The endpoint is a composite created by standardizing and averaging performance across multiple tests. In general, a composite can summarize related domains in one measure, but interpretation depends on the test selection, scoring rules, and handling of unavailable component scores. The registry describes the listed measures and broad standardization process, but details such as component-level missing-data handling and reliability 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("State Regulation Skill Training", "Treatment-as-usual")
n   <- c(6, 6)
m   <- c(0.18, -0.06)
sp  <- c(0.79, 0.72)
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  State Regulation Skill Training  6  0.180  0.790  -0.649  1.009
CARM  Treatment-as-usual  6  -0.060  0.720  -0.816  0.696

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and names 3 posted secondary outcomes: change in event-related potential related to memory retrieval, event-related potential related to memory retrieval, and network modularity from EEG. The record does not report results for these secondary outcomes. It lists 0 analyses, so no analysis results or multiplicity-adjusted findings are available in the registry record.

When a study examines multiple outcomes or multiple tests of the same outcome, the chance of a false-positive finding can rise if each test is judged separately. Statistical approaches can address multiplicity by adjusting significance thresholds or by defining a hierarchy of outcomes in advance. This is a general explanation; the registry record does not report whether any such approach was planned or used, how the primary outcome was prioritized, or how secondary outcomes were handled.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint comparison is identified as having values missing or not estimable for a two-arm continuous comparison. That statement does not explain whether participant-level observations were missing, whether summary values were unavailable, or another issue prevented estimation. It should not be treated as a documented account of why data were unavailable.

The record does not state whether analyses followed intention-to-treat principles, whether participants were excluded from particular analyses, how missing measurements were handled, or whether sensitivity analyses were performed. Those omissions limit interpretation of the reported outcome sample sizes and prevent assessment of the possible effect of missing data on the intended comparison. The listed secondary outcomes and the stated EEG research aim do not substitute for reported statistical analyses.

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 adverse-event record lists State Regulation Skill Training with 9 participants at risk for serious adverse events and 0 affected, and 9 at risk for other adverse events and 0 affected. For Treatment-as-usual, it likewise lists 9 participants at risk for serious adverse events and 0 affected, and 9 at risk for other adverse events and 0 affected. Deaths are listed as 0 in each group. No serious adverse-event terms are listed.

These are registry safety counts, not measures of the cognitive outcome. A count of 0 affected means that no events in that category are recorded for the stated at-risk group in this entry; it does not prove that an event is impossible or that all harms were assessed identically. The registry record does not provide further detail about event definitions, collection methods, follow-up duration, or whether all participants were included in the safety accounting.

The adverse-event at-risk counts differ from the outcome sample sizes attached to the baseline summaries. The record does not explain the difference, so the safety and efficacy denominators should not be treated as interchangeable. The posted counts describe what the registry records and do not, by themselves, establish comparative safety.

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

The registry entry describes a completed, randomized, double-masked, parallel pilot study of state regulation skill training compared with treatment-as-usual. Its primary outcome is a composite attention and executive-function score measured at baseline. The posted arm means and standard deviations are descriptive baseline summaries. They do not report what happened after the intervention period.

The record does not provide an estimable two-arm continuous comparison for the primary endpoint. As a result, it does not establish the magnitude or precision of any difference between the interventions in cognitive outcomes. The baseline values cannot be interpreted as treatment effects, and they do not show whether participants’ scores changed. The registry also lists EEG-related secondary outcomes, but it reports no analyses connecting brain-activity measures with behavioral response.

In general, a pilot trial can help assess the feasibility of a larger evaluation and generate questions for future study, but the registry record does not report specific feasibility outcomes or a formal sample-size justification. Its small posted outcome sample sizes and absent comparison limit how much can be inferred from the available endpoint summaries. No claim about clinical effectiveness, lack of effectiveness, or mechanism is supported by these data alone.

The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths in each group, using the at-risk counts listed in the registry. These counts are descriptive and do not rule out unrecorded events or provide a complete account of safety monitoring. The record does not include enough information to evaluate event ascertainment or longer-term outcomes.

The most defensible reading is narrow: the registry reports baseline composite-score summaries and safety counts, while leaving the main treatment comparison and the proposed EEG-response analyses unavailable. Other relevant details, including the analysis populations, missing-data handling, and statistical plan, are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically interesting because it combines a behavioral training question with an interest in neural markers of variability in response. The trial summary frames the motivation as understanding why responses to training may differ and whether EEG changes can help explain those differences. That raises questions about outcome definition, longitudinal measurement, and how a mechanistic marker would be related to a behavioral endpoint.

The primary measure is a composite assembled from standardized attention and executive-function tests. Composite outcomes can be useful when a research question concerns several related cognitive skills, because they provide a single summary on a common scale. At the same time, interpretation depends on the construction and timing of the measure. Here, the registry specifies a baseline assessment but does not report the later primary outcome comparison. That distinction is central: a well-described endpoint is not the same as an estimable treatment effect.

The record also illustrates why analysis transparency matters in a pilot trial. Outcome sample sizes, adverse-event at-risk counts, and enrollment are reported in different places, but the reasons for the differing counts are not explained. The statistical analysis plan, analysis populations, and missing-data procedures are not reported. Without those details, readers cannot determine how the available summaries relate to the randomized groups or evaluate the planned inferential approach.

Finally, the stated EEG aim would require analyses beyond listing neural outcomes. Connecting a marker to variation in behavioral response needs defined measurements and an analysis that is reported clearly enough to assess. The registry lists EEG-related outcome names but reports no analyses. This makes the distinction between a research hypothesis and a reported result especially important: the record identifies a question of scientific interest without resolving it statistically.

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 central limitation for interpretation is that the primary endpoint is listed at baseline, while the registry does not report an estimable two-arm continuous comparison. The available means and standard deviations cannot establish change during the intervention or a difference between treatment groups. No effect estimate, confidence interval, or p-value for that comparison is reported in the registry record.

The outcome sample size is 6 in each arm, whereas the enrollment figure is 18. The record does not explain the difference or identify which analysis population contributed to the primary summaries. Separately, adverse-event at-risk counts are 9 in each group; their relationship to the outcome sample sizes is not reported. These figures should not be reconciled by assumption.

Eligibility criteria and detailed participant characteristics are not reported in the registry record. The intervention description is incomplete, and the registry does not specify who was masked or how masking was maintained. The treatment schedule, adherence, and other implementation details are also not reported. These gaps limit assessment of the study context and how the interventions were delivered.

The record lists EEG-related secondary outcomes and describes a mechanistic research aim, but reports 0 analyses. It does not provide results on the secondary outcomes or an analysis linking EEG changes to behavioral response. It also does not report a statistical analysis plan, multiplicity procedures, missing-data methods, analysis populations, or a sample-size justification for the original design. The posted information therefore supports descriptive interpretation only, not evaluation of the intended treatment or mechanistic comparisons.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Brain Markers of Improvements in Cognitive Functioning — NCT03490110.
• Registry record last updated 2020-03-23; status last verified 2020-03.
• Results first posted 2020-03-23.
• 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

NCT03490110, titled “Brain Markers of Improvements in Cognitive Functioning,” is listed as a completed randomized, double-masked, parallel study sponsored by the VA Office of Research and Development. Enrollment is 18; the registry lists the phase as NA. The study start is 2017-10-01 and primary completion is 2019-03-01.

The trial compares State regulation skill training with Treatment-as-usual. Its primary outcome is a baseline composite score of attention and executive functioning, reported as a mean with standard deviation. The listed arm summaries are 0.18 with standard deviation 0.79 for training and -0.06 with standard deviation 0.72 for treatment-as-usual; the outcome sample size is 6 for each group. The two-arm continuous comparison is not estimable in the registry record.

The record lists 3 secondary outcomes, including EEG-related measures, and 0 analyses. Serious adverse events, other adverse events, and deaths are each recorded as 0 in both groups. The analysis plan, missing-data approach, and analysis populations are not reported in the registry record.