Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates (NCT01353196), a registered phase not stated study. The primary outcome is Composite Cognitive Score.

2. Clinical Question

The study concerns whether cognitive function differs between participants described as having carotid stenosis and participants described as having no stenosis. Its primary measure is a composite cognitive score, recorded at a timeframe of 2 years. The registry record does not report the group scores, an estimated difference, or an analysis of the relationship between stenosis and cognitive function, so the direction and size of any observed difference are not reported in the registry record.

3. Trial Design

The registry record identifies this study as “Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates” and lists the VA Office of Research and Development as sponsor. Its status is COMPLETED. The listed start date is 2011-05-15, and the primary completion date is 2018-02-28. Enrollment is listed as 170. These record details describe the study’s registration, but do not establish how many participants contributed to the cognitive outcome analysis.

The study has two described arms: carotid stenosis and no stenosis. The registry record explicitly indicates that this is not a randomized comparison and that allocation is not stated. It should not be interpreted as a randomized trial or as a like-for-like control comparison. How participants were assigned to or selected into the arms is not reported in the registry record. Nor are the recruitment process, participant flow, baseline characteristics, or reasons for any differences between the groups reported in the registry record.

The summary describes an investigation of cognitive impairment and possible plaque-related correlates. It refers to imaging of plaque structure and composition, particles breaking off from plaques, blood chemicals that could disrupt them, and restriction of blood flow to the brain. The registry record does not describe an intervention assigned to participants. The primary outcome is a composite cognitive score with a timeframe of 2 years. The record does not give further detail about when or how often cognitive tests were administered, or how the listed timeframe relates to each participant’s assessment.

Although the record is marked completed, the results information available for this analysis does not include numerical cognitive scores or an inferential analysis. Completion status alone does not indicate what the study found or how precisely any relationship was estimated.

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

Analysis population for the primary outcome, as defined in the registry: Participants that did not complete the study or missing key data elements were excluded from the overall analysis

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 Cognitive Score, measured over 2 years.

The primary endpoint is the Composite Cognitive Score, described as a composite of multiple cognitive function test scores. A composite can represent performance across several cognitive tasks in one summary measure; it may be used when a study aims to characterize more than one aspect of cognition. The specific tests, scoring rules, and method used to combine them are not reported in the registry record.

The record describes the score in units on a scale and states that 0 = worst and 100 = best. It specifies reporting as mean +/- standard deviation and gives a timeframe of 2 years. A mean describes the group’s average score, while a standard deviation describes how spread out scores are around that average. These summaries would help readers understand both the average performance and variation among participants if numeric results were available.

The registry record does not report the group means or standard deviations, an estimated between-group contrast, or a confidence interval. Therefore, the scale description explains how a score would be read, but it does not establish the cognitive performance observed in either arm. The record also says that participants who did not complete the study or had missing key data elements were excluded from the overall analysis. The number excluded and the implications for the endpoint results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous outcome summarized as a mean and standard deviation. The statistical concepts below are general explanations of how such results are commonly read; they are not claims that a particular analysis was conducted in this study.

What does a mean describe?

General: a mean is an average across the observations included in an analysis. For a cognitive score, it would provide a central summary of the scores in a group. Comparing group means can describe the direction and size of a difference, but a useful interpretation also needs the uncertainty around that difference and information about how the participants were selected and analyzed. The registry record does not report the mean scores for either arm.

What does a standard deviation describe?

General: a standard deviation summarizes the spread of individual observations around a group mean. A larger standard deviation indicates greater variability in scores within that group; it is not the uncertainty of the mean itself. Standard deviations can help readers see whether an average represents a fairly consistent set of scores or a more variable set. The endpoint description says scores are reported as mean +/- standard deviation, but the numeric standard deviations are not reported in the registry record.

How would a confidence interval help?

General: a confidence interval expresses the statistical uncertainty around an estimate, such as a group mean or a difference between group means. It helps distinguish an estimate that is relatively precise from one that remains compatible with a broad range of values. The interval’s interpretation depends on the analysis and assumptions used. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

What would a p-value add?

General: a p-value, when calculated under a specified statistical model, describes how compatible the data are with a null hypothesis under that model. It does not measure the probability that the null hypothesis is true, nor does it convey the size or practical importance of an effect. A p-value cannot replace an effect estimate and its uncertainty. No p-value or analysis result is reported in the registry record.

Why does the comparison design matter?

General: random assignment can, under appropriate conduct, support comparable groups on average with respect to factors that influence outcomes. This record states that the comparison is not randomized and that allocation is not stated. The group contrast should therefore be read as a comparison between the described arms, not as an isolated causal effect of stenosis. Differences in participant characteristics or other factors could contribute to a contrast. The record does not report an adjusted analysis or enough detail to assess control of potential confounding.

How should planning estimates be read?

General: a sample-size calculation is a planning illustration under stated assumptions, not a result observed in participants and not a measure of the study’s achieved power. The registry record describes a planning approach based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such assumptions explain what a planning illustration represents; they do not establish that the study was designed or conducted according to those assumptions. The registry record does not report its own sample-size justification, and the planning approach should not be mistaken for one.

General: an observed effect used as an input to a planning exercise is distinct from a prospective design target. A planning estimate depends on the chosen effect and statistical assumptions. It cannot repair the absence of a reported outcome estimate, and it does not show what the study found. No numerical planning result is stated in the registry record information.

What can be inferred from the listed analysis information?

The registry record lists one outcome measure and no analyses. That means the record does not provide an inferential method or analysis result for the primary outcome. It does not establish that no analysis occurred outside the registry; it means an analysis is not reported in the registry record. Details such as model specification, covariate adjustment, handling of outliers, and assumption checks are not reported in the registry record. General statistical methods cannot fill in those study-specific details.

General: for a continuous score, analysts commonly consider whether the chosen summary and model suit the distribution and study design. If observations are dependent, for example because of repeated measurements, a model may need to account for that dependence. If the data have strong skew or unusual values, summaries and estimates may be sensitive to those features. These are general considerations, not descriptions of the analysis used; the registry record does not report the information needed to assess them.

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("Stenosis", "no Stenosis")
n   <- c(82, 62)
m   <- c(45.5, 47.9)
sp  <- c(6, 5)
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  Stenosis  82  45.500  6.000  44.182  46.818
CARM  no Stenosis  62  47.900  5.000  46.630  49.170

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure, the Composite Cognitive Score, and no analyses. It does not report a multiplicity strategy, such as whether or how statistical testing across multiple outcomes, time points, or subgroup comparisons was handled. The summary refers to several plaque-related features as areas of investigation, but the record does not list analyses connecting those features to the cognitive score. The extent of any additional analyses is not reported in the registry record. Without the analysis plan and results, readers cannot determine which comparisons were prespecified, whether additional comparisons were made, or how multiplicity may affect interpretation.

The stated analysis population excluded participants who did not complete the study or had missing key data elements. The registry record does not report the number excluded, the amount or pattern of missing data, or the reasons for missingness. It also does not report whether missing values were handled in any other way, such as through imputation or sensitivity analyses. The exclusion statement alone does not show whether missingness was related to cognitive scores or differed between arms.

Group-specific analysis counts, participant flow, and the characteristics of included and excluded participants are not reported in the registry record. Enrollment is listed as 170, but that figure should not be assumed to be the number analyzed for the primary endpoint. Without these details, the potential effect of exclusions on the results and the representativeness of the analyzed group cannot be assessed.

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 record reports zero serious adverse events among 100 at risk in the stenosis group and zero among 70 at risk in the no-stenosis group. It also reports zero other adverse events among 100 at risk in the stenosis group and zero among 70 at risk in the no-stenosis group. These are the counts recorded for the stated at-risk groups; they should not be extended beyond the reporting captured in the registry record.

The record separately lists deaths as 18 for the stenosis group and 11 for the no-stenosis group. It does not report timing, causes, attribution, or an analysis comparing deaths between groups. The death counts should not be interpreted as showing that stenosis caused deaths or that the groups had different risks. No such conclusion follows from counts alone, particularly in a comparison that was not randomized and for which allocation is not stated.

The registry record does not provide further detail about adverse-event definitions, ascertainment, duration of follow-up for safety, or whether the listed at-risk counts correspond to the cognitive analysis population. Zero reported events should therefore be read as the recorded count, not as proof that no events occurred outside the record’s reporting scope.

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

The record describes a completed study of cognitive function in the context of asymptomatic carotid stenosis and plaque-related features. It identifies a composite cognitive score as the primary outcome and distinguishes participants with carotid stenosis from those with no stenosis. These details establish the topic and the intended comparison, but they are not themselves evidence of an outcome difference.

The numerical cognitive results and statistical analyses are not reported in the registry record. As a result, the available information does not show whether scores were higher or lower in either arm, how large any difference was, or how uncertain an estimate might be. It cannot establish that the groups were equivalent, and it cannot establish an association between a specific plaque feature and cognition. Absence of a reported estimate is not a null result.

The design information also limits what could be concluded from a group contrast. The comparison is not randomized, and allocation is not stated. A difference between the groups, if reported, would not by itself demonstrate that stenosis caused a difference in cognitive function. The record does not provide the group characteristics or analysis details needed to assess potential confounding.

The study summary describes an aim to investigate possible mechanisms and identify people who may be at risk for cognitive impairment. The registry record does not report results that establish a mechanism, identify a risk group, or evaluate a preventive measure. It also does not report an intervention comparison. Those broader aims should not be confused with findings from the listed primary endpoint.

In short, the registry documents the research question, design limitations, endpoint definition, and selected safety counts. It does not provide the outcome estimates needed to draw conclusions about cognitive performance across the groups.

14. Why This Trial Matters Statistically

This study is statistically relevant because it asks about cognition in a population described as asymptomatic, using a composite score rather than a single cognitive test. Combining multiple test scores can provide a broader summary of performance, but interpretation depends on the tests selected, how scores are placed on a common scale, and how the composite is constructed. Those details are not reported in the registry record. Their absence makes it difficult to judge what aspects of cognition the measure represents.

The comparison also illustrates why design information matters alongside outcome summaries. The record identifies stenosis and no-stenosis groups but states that the comparison is not randomized and that allocation is not stated. A statistical contrast between such groups can describe a difference, if one is reported, but cannot by itself separate the relationship with stenosis from other differences between participants. The registry record does not report an adjusted analysis that could be assessed for this purpose.

Another important statistical issue is the analysis population. Participants who did not complete the study or had missing key data elements were excluded from the overall analysis. Exclusions can affect how representative analyzed participants are, depending on who is missing and why. The record does not provide the counts or missing-data patterns needed to examine that issue.

Finally, the lack of reported score estimates and analyses limits the value of the record for assessing precision. A complete interpretation ordinarily requires an effect estimate and uncertainty, not just a study question or completion status. The record’s stated planning approach is not a substitute for observed results or for the study’s own design justification.

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.

Several limitations specific to this record constrain interpretation. The primary endpoint is defined as a composite of multiple cognitive function test scores, but the individual tests and method of combining them are not reported in the registry record. The scale is described, yet no group means, standard deviations, or estimated contrast are reported. This prevents assessment of the direction, magnitude, and precision of the primary outcome.

The comparison is not randomized, and allocation is not stated. The registry record does not report how participants came to be in either arm, or provide group characteristics that would help assess comparability. It also does not report a statistical model or adjusted analysis. As a result, potential confounding cannot be evaluated from the record.

The endpoint description states that participants who did not complete the study or had missing key data elements were excluded from the overall analysis. The number and characteristics of excluded participants, the amount and pattern of missing data, and sensitivity analyses are not reported in the registry record. This leaves uncertainty about how exclusions may affect the analyzed population.

The summary describes plaque-related measurements and possible mechanisms, but no corresponding results or analyses are reported. The record also does not report detailed safety definitions, event timing, or causes of the listed deaths. These omissions limit interpretation of both the scientific aims and the safety counts. The COMPLETED status and listed enrollment do not resolve these reporting gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates — NCT01353196.
• Registry record last updated 2019-07-24; status last verified 2019-05.
• Results first posted 2019-07-24.
• 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 record for NCT01353196 is titled “Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates.” The sponsor is the VA Office of Research and Development, the status is COMPLETED, and enrollment is listed as 170. The start date is 2011-05-15, and the primary completion date is 2018-02-28.

The record describes arms with carotid stenosis and no stenosis and identifies the Composite Cognitive Score as the primary outcome, with a timeframe of 2 years. The comparison is not randomized, and allocation is not stated. Participants who did not complete the study or had missing key data elements were excluded from the overall analysis.

Numeric cognitive results and analyses are not reported in the registry record. The record lists adverse-event counts and deaths for the two groups, but does not report details needed to interpret causes or comparative risks.