Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI) (NCT01021137), a registered phase not stated study. The primary outcome is Peripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness.

2. Clinical Question

3. Trial Design

The registry record describes a completed study sponsored by the VA Office of Research and Development, with enrollment of 140. The study start is listed as 2011-05-01 and primary completion as 2016-12-30. Its stated purpose was to determine the effects of mild traumatic brain injury and blast exposure on inner-ear balance and central nervous systems.

The listed groups are TBI & Blast, Blast Only, TBI Only, and Healthy Controls. The first three groups consist of OEF/OIF veterans complaining of dizziness and/or imbalance, classified by their reported blast exposure and TBI history. Healthy controls are described as age- and gender-matched participants without dizziness or imbalance complaints and without a history of TBI or blast exposure. A separate Excluded category describes people who did not meet inclusion criteria, did not return to complete evaluation, and/or were excluded from data analysis; it should not be treated as a comparison group.

This is not a randomized comparison. Allocation is not stated in the registry record, and the listed groups are not a like-for-like control comparison. Their differences in symptoms and exposure histories are central to interpreting any contrast: a group difference would not, on its own, isolate a causal effect of blast exposure or TBI. The registry record does not describe the recruitment process, the rules used to assign participants to groups, or whether the reported enrollment corresponds to the analysis population for each outcome.

The primary endpoint is caloric weakness, a continuous measure of peripheral vestibular function. Secondary outcomes listed are visual fixation suppression, the Sensory Organization Test for postural stability, and the Dizziness Handicap Inventory. The record lists 8 outcome measures in total, but does not identify all of them in the registry record for this account. It lists no analyses. The numbers analyzed in each group, the handling of exclusions, and the statistical plan 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.

Before assignment: Six participants were consented to participate in the study, but did not return to complete the protocol. Case history was not collected and therefore, the participants could not be assigned to any of the study groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group.

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.

Population: The overall number of baseline participants differs from the number of participants assigned to the groups due to participants being lost to follow-up and being withdrawn from the study.

6. Primary Endpoint

The registry lists the primary outcome as Peripheral Vestibular Function (Vestibulo-ocular Reflex/Semicircular Canal): Caloric Weakness, measured over up to 30 minutes.

The primary endpoint is peripheral vestibular function, assessed through the vestibulo-ocular reflex and semicircular canal response. It is reported as percentage of caloric weakness and summarized using the mean and standard deviation. The registry timeframe is up to 30 minutes.

Caloric weakness is based on the difference between responses from the two ears during water irrigation. The registry description uses monothermal warm inter-ear difference (MWIED) to calculate an initial measure from the warm-water responses. For participants with MWIED > 10, cool caloric irrigation was also performed, and the endpoint was determined using a bithermal inter-ear difference (BIED) that incorporates warm- and cool-water responses. The detailed registry description defines the response using the maximum slow phase velocity of irrigation-induced nystagmus from each ear.

As a general statistical and measurement point, comparing responses between ears can help characterize asymmetry in the measured vestibular response. A group mean can describe the average endpoint value, while the standard deviation describes spread among observations; neither alone shows the range of individual results or the precision of a group comparison. Interpretation also depends on consistent measurement and on which participants have usable endpoint data. The registry record says caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group.

The endpoint definition is reported, but its group means, standard deviations, and comparative estimates are not reported in the registry record. The endpoint description therefore explains what was intended to be measured, not what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies caloric weakness as a continuous primary outcome, summarized as a mean with standard deviation. It names several other outcome measures but lists no analyses. The methods used to compare groups, estimate uncertainty, or account for other participant characteristics are not reported in the registry record. The explanations below are general statistical context, not a description of analyses known to have been performed in this study.

What does a mean describe?

In general, a mean is a measure of the center of a set of observations. For a continuous outcome such as percentage of caloric weakness, it offers a compact description of the average measured value among the observations included in a group summary. It does not show whether observations are clustered near that average or spread widely, and it can be affected by unusually high or low values. A mean is most informative when read alongside a measure of spread and a clear account of the participants included.

The registry names standard deviation as the measure of spread. In general, standard deviation describes how dispersed individual observations are around the mean. It is not the same as uncertainty in the mean: that uncertainty also depends on how many observations contribute and on the analysis method. Group means and standard deviations for the primary outcome are not reported in the registry record, so no numerical description of the observed distributions is available.

How should an interval estimate be read?

In general, a confidence interval gives a range of values compatible with an estimate under a statistical model and its assumptions. It expresses uncertainty in the estimated quantity; it is not a range containing all individual participant values, nor does it by itself establish clinical importance or causation. The width and location of an interval can help readers judge how precisely a contrast was estimated. Confidence intervals for the primary endpoint are not reported in the registry record.

A p-value, in general, measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It does not give the probability that the null hypothesis is true, and it does not measure the size of a group difference. No p-value or other inferential result for the primary endpoint is reported in the registry record. The record lists no analyses, so it does not establish which inferential procedure, if any, was used.

What does the endpoint calculation represent?

The endpoint is based on the difference between vestibular responses from the right and left ears during caloric water irrigation. The registry description says that MWIED is calculated using the warm-water responses, and that cool irrigation is also performed for participants with MWIED > 10; for those participants, caloric weakness is determined using BIED, which uses warm- and cool-water responses. The registry defines the response through the maximum slow phase velocity of irrigation-induced nystagmus. This describes the measurement procedure; it does not supply evidence about the validity or reliability of that procedure in this study. Further information on measurement reliability is not reported in the registry record.

In general, an endpoint that incorporates responses from both ears can represent asymmetry in the measured response. The resulting percentage is a continuous value, and a group summary can conceal differences among individuals. Measurement availability also affects who contributes to a summary. The record notes that caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group. It does not explain why the values were unavailable or report how the analysis addressed them.

Why does the group structure affect methods?

Methods for randomized trials often rely on allocation to make treatment groups comparable on average, but this study is not described as randomized. Allocation is not stated, and the registry explicitly characterizes the arms as not a like-for-like control comparison. General statistical principle: an unadjusted difference between groups in a nonrandomized study can reflect differences in characteristics other than the exposure history being considered. Statistical adjustment can sometimes account for measured characteristics, but it cannot guarantee removal of bias from unmeasured or poorly measured factors. Whether any adjustment was performed is not reported in the registry record.

Comparisons among the symptomatic veteran groups may address different exposure histories, while comparison with healthy controls also contrasts symptom status and exposure history. These are not interchangeable questions. The record does not report a prespecified primary contrast, covariates, model form, or tests of assumptions. It is therefore not possible to identify which particular contrast was intended to carry the main inferential interpretation.

What do the planning assumptions mean?

The sample-size assumptions describe planning illustrations based on the observed effect, not the original trial design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. In general, a planning calculation estimates the sample size needed to detect a specified effect under stated assumptions. It depends on the chosen effect, variability, allocation, statistical test, and target power. These assumptions cannot be treated as evidence that the study had a particular prespecified design or that it achieved a particular level of power.

Such sample-size illustrations are not observed power. Observed power is not a substitute for reporting the estimated effect and its uncertainty. The registry record does not report the trial’s sample-size justification, statistical plan, or interim analyses. It also does not report the numerical primary endpoint effect needed to interpret a calculation framed as a fraction of that effect. Accordingly, planning illustrations can describe hypothetical future study requirements under their assumptions, but they do not fill the gap in the reported outcome results.

The record lists 8 outcome measures and names several secondary outcomes, but the statistical approach to multiple outcomes is not reported. In general, evaluating many outcomes can increase the chance of finding at least one apparently notable result by chance if no multiplicity strategy is used. A prespecified hierarchy or adjustment may address that issue, but no such strategy is reported. The absence of a reported strategy should not be taken to mean that one was or was not used.

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("TBI & Blast", "Blast Only", "TBI Only", "Healthy Controls")
n   <- c(52, 15, 9, 30)
m   <- c(8.8, 14.7, 12.3, 7.1)
sp  <- c(8.5, 20.8, 5.6, 6)
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  TBI & Blast  52  8.800  8.500  6.434  11.166
CARM  Blast Only  15  14.700  20.800  3.181  26.219
CARM  TBI Only  9  12.300  5.600  7.995  16.605
CARM  Healthy Controls  30  7.100  6.000  4.860  9.340

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures. It names visual fixation suppression for central vestibular/central nervous system function, the Sensory Organization Test for postural stability, and the Dizziness Handicap Inventory as secondary outcomes. The statistical treatment of the full set of outcomes is not reported in the registry record. In particular, it does not state whether one outcome was designated as the sole basis for confirmatory inference, whether a hierarchy was specified, or whether any adjustment for multiple comparisons was planned or used.

As a general statistical point, examining several outcomes or several group contrasts can create multiple opportunities for apparently noteworthy results. Multiplicity methods can control or describe that issue, but their use and interpretation depend on the analysis plan. The record lists no analyses and does not report a multiplicity procedure. No conclusion about the presence or absence of multiplicity adjustment can therefore be drawn.

For the primary outcome, caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group. The reasons are not reported. The registry record does not say whether unavailable measurements were excluded from the endpoint summaries, imputed, or handled by another approach. It also does not report missingness for the secondary outcomes or a sensitivity analysis addressing missing data.

The registry describes an Excluded category that includes people who did not meet inclusion criteria, did not return to complete evaluation, and/or were excluded from data analysis. The number in that category and the criteria applied to each reason are not reported in the registry record. The record also does not identify an analysis population, provide participant flow for each endpoint, or state whether all enrolled participants were eligible for every analysis. Enrollment of 140 is therefore not enough to determine the denominator for any particular outcome.

In general, missing data can affect an estimate if the availability of a measurement is related to participant characteristics or outcome values. Without reasons for missingness, analysis denominators, and the handling method, the direction or extent of any effect cannot be assessed from the registry record.

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 no serious adverse events and no other adverse events in the four listed groups. In TBI & Blast, 0 serious events and 0 other events were reported among 62 at risk; deaths were 0. In Blast Only, 0 serious events and 0 other events were reported among 20 at risk; deaths were 0. In TBI Only, 0 serious events and 0 other events were reported among 11 at risk; deaths were 0. In Healthy Controls, 0 serious events and 0 other events were reported among 41 at risk; deaths were 0.

These figures describe events recorded in the registry for the listed groups. They do not establish that no event could occur, and they do not quantify risk beyond the observation and reporting conditions used in the study. The registry record does not report the safety observation period, event definitions, collection procedures, or whether the event counts were assessed using a particular attribution method. No serious adverse-event terms are listed.

As a general statistical point, zero recorded events should be read as an observed count, not as proof of zero underlying risk. These safety counts also do not provide evidence about the primary vestibular endpoint or the comparative effects of the exposure histories.

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

The registry record identifies a study question about vestibular consequences associated with blast exposure and mild TBI. It describes symptomatic veterans in groups defined by those histories and age- and gender-matched healthy controls. It also specifies a primary measure of caloric weakness and names secondary measures involving visual fixation suppression, postural stability, and dizziness-related handicap. These details establish what the study intended to examine.

They do not establish the size or direction of any observed group difference. Group-level primary outcome results, measures of uncertainty, and statistical comparisons are not reported in the registry record. The record lists no analyses. As a result, it is not possible to say from these registry entries whether any groups differed on caloric weakness or how precisely a difference was estimated. Results for the named secondary outcomes are also not reported in the registry record.

The design also limits causal interpretation. This is not a randomized comparison, allocation is not stated, and the groups are not a like-for-like control comparison. General statistical principle: group contrasts in a nonrandomized design can reflect differences beyond the exposure history of interest. A finding of association, if reported elsewhere, would not automatically establish that blast exposure or TBI caused it. The registry record does not provide the analyses or participant characteristics needed to assess adjustment for potential confounding.

The primary measurement could not be obtained for 1 participant in the Blast Only group and 2 participants in the Healthy Control group. The reasons and analytic handling are not reported. Thus, the enrollment figure of 140 should not be read as the number contributing to each endpoint, and the precision of any analysis cannot be inferred from enrollment alone.

The safety record lists zero serious adverse events, zero other adverse events, and zero deaths in each of the four listed groups. Those counts are observations in the registry, not proof that the underlying risk is absent. Overall, the registry provides useful information about the intended measurements, group definitions, and recorded safety counts, but it does not provide enough outcome or analysis information to characterize efficacy, causal effects, or statistical precision.

14. Why This Trial Matters Statistically

This study is statistically noteworthy because its central question involves separating the contributions of two related exposure histories: blast exposure and mild TBI. The group definitions make those histories explicit, with groups for both, blast exposure without TBI, and TBI without blast exposure. A healthy control group offers a further reference, but it differs from the symptomatic veteran groups in symptoms as well as exposure history. These distinctions matter when deciding what a contrast can mean.

The study also illustrates why a well-defined measurement does not by itself answer a clinical research question. Caloric weakness is described in considerable technical detail, including the use of warm-water responses and, for participants with MWIED > 10, cool-water testing. Yet the registry record does not report group means, standard deviations, or inferential comparisons. Readers can understand the intended endpoint but cannot evaluate the observed group pattern or its precision from the registry information.

The record further highlights the importance of analysis populations and missing measurements. Caloric weakness was unavailable for some participants in two groups, while the handling of those values is not reported. Enrollment alone does not indicate how many observations contributed to each outcome. Clear denominators, participant flow, and missing-data methods are needed to understand whether an endpoint summary represents the intended population.

Finally, the registry lists several outcomes and no analyses. General statistical practice calls for transparent reporting of prespecified outcomes, contrasts, methods, and multiplicity decisions so readers can distinguish planned inference from exploratory comparisons. Those details are not reported in the registry record. This limits what can be learned from it statistically, independently of the importance of the research question.

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 most consequential limitation for interpreting the registry record is that group-level results for the primary endpoint are not reported. Means, standard deviations, comparative estimates, confidence intervals, and p-values are absent in the registry record for this account. The record therefore supports describing the measurement and study structure, but not the size, direction, or precision of any primary outcome contrast.

The design is not randomized, allocation is not stated, and the arms are not a like-for-like control comparison. The symptomatic veteran groups and healthy controls differ by symptom status and exposure history as described in the registry. Recruitment methods, group assignment procedures, baseline characteristics, and potential confounding factors are not reported in the registry record. Those omissions prevent a fuller assessment of comparability.

Caloric weakness could not be obtained from 1 participant in the Blast Only group and 2 participants in the Healthy Control group. Why those measurements were unavailable and how they were handled are not reported. The registry also describes an Excluded category but does not give its size or reasons by participant. Outcome-specific analysis denominators and missing-data sensitivity analyses are not reported.

Although the record lists 8 outcome measures, it names only several secondary outcomes in the registry record. The statistical plan, exact group contrasts, covariate adjustments, assumptions, multiplicity procedures, and interim analyses are not reported in the registry record. Nor is the original sample-size justification reported. The planning assumptions associated with illustrative calculations should not be mistaken for the study’s own design or evidence of observed power.

The safety entries report zero events, but the observation period and event collection details are not reported. These limitations restrict interpretation of both the study’s outcome evidence and the scope of its safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vestibular Consequences of Blast-related Mild Traumatic Brain Injury (TBI) — NCT01021137.
• Registry record last updated 2019-08-05; status last verified 2019-06.
• Results first posted 2019-08-05.
• 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 describes a completed study sponsored by the VA Office of Research and Development, with enrollment of 140. The stated aim was to examine effects of mild TBI and blast exposure on inner-ear balance and central nervous systems. Groups include symptomatic veterans with both histories, blast exposure without TBI, or TBI without blast exposure, plus healthy controls. The study is not a randomized comparison, allocation is not stated, and the arms are not a like-for-like control comparison.

The primary endpoint is percentage of caloric weakness, summarized as a mean and standard deviation, with a timeframe of up to 30 minutes. Secondary outcomes named include visual fixation suppression, the Sensory Organization Test, and the Dizziness Handicap Inventory. The registry lists 8 outcome measures but no analyses. Group-level outcome results and the statistical plan are not reported in the registry record. Caloric weakness was unavailable from 1 participant in the Blast Only group and 2 participants in the Healthy Control group. The listed groups each have 0 serious adverse events, 0 other adverse events, and 0 deaths.