Neural Bases of Cognitive Rehabilitation for Brain Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neural Bases of Cognitive Rehabilitation for Brain Injury (NCT01120756), a randomized na study. The primary outcome is Change From Baseline on a Composite Measure (Z-score) of Attention, Working Memory, and Executive Functions.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, single-masked, parallel-group study of behavioral interventions for brain injury. The two arms were goal-oriented attentional self-regulation training and Brain Health Education. The listed enrollment is 35, and the study status is completed. The record identifies the VA Office of Research and Development as sponsor.

The primary outcome is a continuous composite measure, reported as a mean change from baseline. The arm-level results list 20 participants for GOALS and 13 for Brain Health Education. The outcome description reports loss to follow-up from baseline to follow-up, with one participant lost from each arm. These outcome counts should be read as reported for the posted result, rather than as a complete account of every participant enrolled or randomized.

The outcome timeframe is baseline and within 2-3 weeks after the intervention. The registry also lists a functional secondary outcome measured at baseline and 2-3 weeks post-intervention. The study therefore reports short-term changes on cognitive and functional measures; a longer-term assessment is not reported in the registry record.

The record identifies the design as randomized and single-masked, but the randomization procedure, the identity of the masked party, and the procedures used to maintain masking are not reported in the registry record. Details about intervention duration, adherence, allocation concealment, and the original rationale for the enrollment target are also not reported in the registry record. The record lists phase as not applicable.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: We lost a total of n=2 participants to attrition from baseline to follow-up. This included n=1 from the Goal-Oriented Attentional Self-regulation training and n=1 from the Brain Health Education.

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 From Baseline on a Composite Measure (Z-score) of Attention, Working Memory, and Executive Functions, measured over Baseline, Within 2-3 weeks Post-intervention.

The primary endpoint is change from baseline on a composite measure of attention, working memory, and executive functions. The registry describes combining participants’ scores from commonly used neuropsychological tests. Individual performances were first scored using published norms, adjusted for demographic characteristics when available. Scores from different tests were then converted to a common z-score scale, and each participant’s test z-scores were averaged to create the composite. The composite, rather than each test considered separately, was the unit of analysis.

As a general statistical interpretation, a composite can bring several related measures into a shared summary, reducing reliance on any single test. The registry explains that a z-score expresses a score in standard-deviation units relative to a reference mean: zero represents the mean, while positive and negative values indicate positions above or below it. The reported endpoint is a change score, so the arm means describe change rather than a post-intervention level alone.

The rationale for using this outcome is connected to the study’s stated focus on attention and executive processes involved in goal-directed behavior. The record does not report the separate results for each neuropsychological test contributing to the composite.

7. Results Posted in the Registry

• Brain Health Education: mean 0.01 versus 0.26 on control; difference -0.25 (95% CI -0.43 to -0.07), standardized effect d = -0.95; z-test p = 0.007.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Functional Evaluations: Change From Baseline on the Goal Processing Scale

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Brain Health Education: mean 0.01 versus 1.05 on control; difference -1.04 (95% CI -1.56 to -0.52), standardized effect d = -1.14; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Brain Health Education than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists a functional secondary outcome based on change from baseline on the Goal Processing Scale. The posted arm means follow the same general direction as the primary comparison: the GOALS arm has a higher mean change than the Brain Health Education arm. This directional agreement may be of interest because the secondary measure addresses functional evaluation rather than the neuropsychological composite itself.

The secondary measure is not a duplicate of the primary endpoint. It uses a different scale and represents a related but distinct outcome domain. Agreement in direction does not establish that both measures capture the same underlying effect, and results across correlated measures should not be treated as independent replications. Nor does an association between the two posted patterns show that change in one measure caused change in the other.

The registry reports an unadjusted comparison for the secondary measure, with p < 0.001, but no reported secondary analysis records. Since this is a secondary result, it generally carries less confirmatory weight than a prespecified primary result, especially when the number of outcomes considered and the handling of multiple comparisons are unknown. The number and scope of other outcomes examined are not fully described in the registry record.

As a general statistical point, evaluating several outcomes increases the chance that at least one result will appear unusually strong even when there is no underlying effect. Adjustment procedures or a clear hierarchy of outcomes can address that concern, but the registry record does not report whether either was used. The secondary finding is therefore best read as additional descriptive evidence that is consistent in direction with the primary pattern, not as independent confirmation.

The registry does not report a threshold for meaningful change on the Goal Processing Scale or details of its measurement properties in this study. The short interval after intervention also limits interpretation to the assessment period recorded. The secondary outcome can broaden the description of the trial’s findings, but it does not resolve uncertainty about missing data, analysis choices, or longer-term patterns.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Functional Evaluations: Change From Baseline on the Goal Processing Scale

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous and summarized with a mean and standard deviation in each arm. A mean represents the arithmetic average of the observed change scores. A standard deviation describes how much individual scores vary around that average. It does not directly describe the precision of the estimated mean difference; that is addressed by the confidence interval.

What does the mean difference represent?

The comparison reports Brain Health Education relative to GOALS. It is expressed as a mean difference in change scores: -0.25. The negative direction matches the posted arm means, where the Brain Health Education mean is 0.01 and the GOALS mean is 0.26. In plain terms, the reported average change was lower in the Brain Health Education arm than in the GOALS arm. The metric is on the composite z-score scale, not a count of correct answers or a raw score from one test.

As a general statistical concept, a mean difference preserves the scale of the measured outcome, which can make its direction and magnitude easier to connect to the measurement than a standardized effect size. A standardized effect size expresses a difference relative to variability. The registry record includes a standardized comparison statistic, but the direct mean difference and confidence interval remain the most interpretable quantities for describing the posted primary result. No clinical threshold for interpreting the composite difference is reported in the registry record.

What does the z-score composite measure?

The registry states that scores from commonly used neuropsychological tests were standardized using published norms, with adjustment for age, gender, ethnicity, and education levels when available. Different score types were converted into z-scores, then averaged for each participant. This method puts test results on a common standardized scale before combining them. As a general explanation, standardization is useful when component tests use different scoring ranges, but it does not make every component equally reliable or equally important. The registry record does not report the specific tests, component-level results, or weighting beyond the described averaging.

The outcome is a change from baseline. That makes the comparison about change over the assessment period rather than simply comparing the final scores. The registry record does not report the baseline arm means or a model adjusting for baseline values. It also does not report whether the change score was analyzed with a particular parametric test or regression method.

How should the p-value be read?

The primary unadjusted p-value is 0.007. As a general statistical explanation, a p-value describes how compatible the observed data are with a specified null model, assuming that model and the test assumptions apply. A smaller p-value indicates that the observed data would be less expected under that null model. It does not quantify the probability that the intervention has an effect, the probability that the result is due to chance, or the clinical importance of the difference.

The registry record does not report the test used to calculate the p-value, the assumptions checked, or whether the p-value was adjusted for multiple comparisons. The arm-level summaries and the unadjusted comparison do not disclose all details needed to reproduce or fully evaluate the analysis.

Why does variability matter?

As a general principle, the uncertainty of an estimated difference depends on both the amount of variability and the amount of information in each group. Greater variability makes it harder to distinguish a group difference from sampling fluctuation, while more observations can improve precision. Here, the primary outcome standard deviations are 0.27 and 0.25, and the outcome counts are 20 and 13. The registry’s reported confidence interval incorporates uncertainty in the comparison, although the method used to construct it is not reported in the registry record.

Standard deviation and standard error answer different questions. Standard deviation describes spread among individual observations; standard error describes uncertainty in an estimated statistic. The posted comparison includes arm-level standard errors, but interpretation should prioritize the directly reported confidence interval for the mean difference. The registry record does not report how its analysis accounted for the randomized design, missing observations, or any possible departures from model assumptions.

What can be concluded from the posted analysis?

The posted statistics support describing an observed difference in mean change between the two arms, with uncertainty summarized by the confidence interval and the unadjusted p-value. They do not by themselves establish that the intervention caused the difference or that the difference is clinically meaningful. Causal interpretation in a randomized study depends on sound conduct, valid outcome measurement, appropriate handling of missing data, and suitable analysis. Several of those methodological details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -0.25, with a reported confidence interval that excludes zero. The interval gives a range of values compatible with the observed data under the interval’s statistical method and assumptions. Because the full interval is reported in the registry but its construction method is not described, the bounds can be read as a measure of statistical uncertainty without assuming a particular model or procedure.

The interval’s exclusion of zero is consistent with the unadjusted p-value of 0.007. The p-value and interval are related summaries of evidence for the comparison, but they do not answer exactly the same interpretive question: the interval also conveys the range and scale of plausible differences under the analysis. It does not account for uncertainty about study conduct, outcome selection, or unreported analysis decisions.

The group standard deviations, 0.27 and 0.25, indicate that individual change scores varied around their group means. The outcome counts are 20 for GOALS and 13 for Brain Health Education. With this amount of information, the estimate remains uncertain even though the interval excludes zero. Statistical precision is not the same as clinical importance, and no threshold for a meaningful difference is reported in the registry record.

The registry record does not report the confidence-interval method or whether its analysis adjusted for covariates. It also does not report multiplicity adjustment. Accordingly, the interval should be interpreted as precision for the posted comparison, rather than as a complete accounting of uncertainty across all outcomes or analytical choices.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning display gives participants per arm, not total events. Its assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The original trial’s own sample-size justification and design assumptions are not reported in the registry record.

The 80% power column gives the planned participants per arm for a design with an 80% chance of detecting the specified effect, if the planning assumptions hold and that effect is present. The 90% power column uses a higher target chance of detection under those same assumptions. For the primary comparison, the planning figures are 18 and 24 participants per arm for 100% of the observed effect; 31 and 42 for 75% of the observed effect; and 70 and 93 for 50% of the observed effect. The first value in each pair is for 80% power and the second for 90% power.

Smaller target effects require more participants per arm because they are harder to distinguish from sampling variability. These values are planning illustrations based on the observed effect, not observed power. They should not be read as evidence that the completed study had a particular probability of finding a result, nor as a reconstruction of the trial’s original design plan. The displayed assumptions are separate from the unreported decisions used to plan the trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.250; pooled standard deviation σ = 0.262.
2. n = 2 × (1.96 + 0.842)² × 0.262² / -0.250² = 17.3, rounded up to 18 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.25                      # observed difference in means
sigma <- 0.262438932988966                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1120756)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 31 (80% power), 42 (90% power)
 50% of observed effect: n per arm = 70 (80% power), 93 (90% power)
power.t.test: 18.3 
Simulated power at n = 18 per arm: 0.791 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the primary and secondary outcomes were arranged in a formal testing hierarchy, whether p-values were adjusted for multiple comparisons, or whether multiplicity was considered in another way. This matters because testing multiple outcomes can increase the likelihood of a nominally unusual result. The unadjusted p-values should therefore be interpreted as tests for their respective comparisons, not as evidence that the overall family of outcomes met a prespecified error-control plan.

The record identifies one primary outcome and one posted secondary outcome, but it does not report whether additional outcomes were assessed or how outcomes were selected for posting. It also does not report interim analyses or stopping rules. These details cannot be inferred from the fact that the study is completed.

The primary outcome description reports loss from baseline to follow-up, with one participant lost from each arm. The registry record does not report why the participants were lost, whether missingness was related to measured or unmeasured characteristics, or what methods were used to handle missing outcome data. It does not say whether imputation, a complete-case analysis, or another approach was used. Consequently, the posted outcome counts alone do not establish how attrition affected the estimate.

The registry record does not report the analysis population, including whether the comparison followed an intention-to-treat principle or used another population definition. It does not describe protocol deviations, treatment adherence, or how participants were handled if they did not receive the assigned intervention. These are important details for interpreting a randomized comparison because exclusions after randomization can affect the balance created by random assignment.

There are no analysis records listed in the registry record. The record therefore does not provide a detailed statistical analysis plan, the model or test used, covariate adjustment decisions, or diagnostic checks. These omissions do not show that no such procedures were used; they mean that those procedures are not reported in the registry record. The posted summary comparison can be described, but its full analytical context remains uncertain.

15. 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 serious adverse event figures report zero affected participants in the GOALS group among 21 at risk and zero in the Brain Health Education group among 14 at risk. The death counts are zero in both groups. No serious adverse event terms are listed.

These figures describe what was recorded in the registry for the specified risk groups. They should not be interpreted as proof that no adverse events of any kind occurred, or that the interventions have no safety concerns. The record also lists zero participants with other adverse events in the risk groups, but does not provide further event descriptions. The registry record does not report event-collection procedures, definitions, follow-up details for safety, or whether the reported risk groups correspond to the outcome-analysis populations.

As a general statistical point, an absence of reported events in a study does not establish that the underlying event risk is zero. Safety estimates are limited by the amount of observation and by how completely events are collected and recorded. The figures are descriptive registry results, not a substitute for a broader safety assessment.

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

The posted results describe a randomized comparison of goal-oriented attentional self-regulation training with Brain Health Education in people with brain injury. On the primary composite outcome, the GOALS arm had a higher mean change than the education arm, and the unadjusted comparison’s confidence interval excludes zero. A related functional secondary measure shows a directionally similar pattern. These are descriptions of the recorded outcomes over the short post-intervention assessment period.

The findings do not establish the clinical importance of the difference. The registry record does not report a threshold for meaningful change on the composite or the secondary scale. The z-score composite standardizes scores across component tests, but its scale does not itself determine whether a given difference matters to participants’ everyday functioning. The functional measure provides a related perspective, but it cannot substitute for a reported clinical interpretation threshold.

The results also do not establish how durable any observed change may be. Follow-up is reported within 2-3 weeks after intervention, and longer-term outcome data are not reported in the registry record. Nor do the posted summaries establish how missing data, adherence, or protocol deviations may have affected the comparisons.

Randomization is a design feature intended to support fair group comparisons, but full interpretation also depends on how randomization was implemented, whether masking was maintained, and how the analysis handled participants and missing measurements. Those details are not reported in the registry record. The unadjusted p-values do not resolve these uncertainties or account for unreported multiple testing.

The appropriate reading is therefore bounded: the registry reports short-term group differences in mean change on the listed measures, with statistical uncertainty summarized for the comparisons. It does not, on its own, establish a treatment recommendation, a mechanism, or a general result for all people with brain injury.

17. Why This Trial Matters Statistically

This trial is statistically informative because it reports a continuous composite built from measures of attention, working memory, and executive functions, alongside a functional secondary measure. The primary outcome description explains how different neuropsychological test scores were transformed to a common z-score scale and averaged. That makes the construction of the composite more interpretable than a result label alone, even though component-level scores are not reported.

The comparison illustrates why effect estimates, uncertainty intervals, and p-values answer related but distinct questions. The mean difference describes the estimated scale and direction of the group contrast; the confidence interval conveys uncertainty around that estimate; and the unadjusted p-value addresses compatibility with a null model under the test assumptions. Reading these together is more informative than treating a p-value as a complete summary.

The record also makes clear that secondary outcomes need a different interpretive status from a primary outcome. A similar direction across a cognitive composite and a functional measure can be descriptively coherent, but multiplicity and the absence of a reported analysis plan leave the confirmatory strength uncertain. This is a useful example of the distinction between consistency of observed patterns and independent confirmation.

Finally, the registry’s missing methodological details matter. Attrition is reported, but the handling of missing outcomes and the analysis population are not. Sample-size planning illustrations are available, but they are not the trial’s original justification. Recognizing these boundaries is part of statistical interpretation: a result can be described precisely while still leaving important questions about robustness, generalizability, and practical meaning unresolved.

18. Limitations

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

Several limitations specific to this trial affect interpretation of the posted results. The primary assessment is short-term, occurring within 2-3 weeks after intervention. Longer-term persistence of the observed changes is not reported in the registry record. The outcome summaries also reflect attrition between baseline and follow-up, with one participant lost from each arm, but the reasons and missing-data procedures are not reported.

The primary endpoint combines scores from multiple neuropsychological tests. Although the registry describes the standardization and averaging process, it does not list the component tests or provide their separate results. This limits assessment of whether the composite pattern was consistent across domains or driven by particular measures. The record also does not report a threshold for clinically meaningful change on either the composite or the functional secondary measure.

Methodological details relevant to a randomized study are not reported in the registry record, including the randomization procedure, the masked party, the allocation-concealment approach, and the analysis population. The statistical test or model, covariate adjustments, handling of protocol deviations, and assumptions checks are also not described. These gaps make it difficult to evaluate the full analysis strategy from the posted summaries alone.

Multiplicity is another uncertainty: the record does not state whether secondary comparisons were adjusted or whether there was a prespecified hierarchy. The registry lists no analysis records, so a detailed analysis plan cannot be assessed. Finally, the planning figures are illustrations based on the observed effect, not documentation of the original trial design rationale. These limitations do not invalidate the posted estimates, but they narrow the conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Neural Bases of Cognitive Rehabilitation for Brain Injury — NCT01120756.
• Registry record last updated 2019-08-02; status last verified 2019-06.
• Results first posted 2019-08-02.
• 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.

22. Record Summary

The registry record describes a completed, randomized, single-masked, parallel-group behavioral study sponsored by the VA Office of Research and Development. It compares goal-oriented attentional self-regulation training with Brain Health Education in people with brain injury. Listed enrollment is 35.

The primary outcome is change from baseline on a composite z-score measure of attention, working memory, and executive functions. The posted comparison reports a mean difference of -0.25 for Brain Health Education relative to GOALS, with an unadjusted p-value of 0.007 and a confidence interval excluding zero. One functional secondary outcome is also posted, with a directionally similar arm pattern.

The record reports attrition, but does not describe missing-data methods, the analysis population, the analysis model, or multiplicity handling. Results are short-term, and longer-term outcomes and thresholds for meaningful change are not reported in the registry record.