Assessment of Dystussia in Traumatic Brain Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Dystussia in Traumatic Brain Injury (NCT02240329), a na early/phase 1 study. The primary outcome is Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration.

2. Clinical Question

3. Trial Design

This is a completed, single-group study of cough and respiratory measures in people with traumatic brain injury. The registry lists the phase as EARLY PHASE1 and an enrollment of 4. The study began in 2013-03, with primary completion in 2015-06. The sponsor is the University of Florida. These details describe the registered study, but do not establish how many participants contributed data to each outcome.

The arm is described as individuals who sustained a traumatic brain injury during the previous five years. The planned assessments included neuropsychological testing and measures of TBI severity, cough and respiratory measures including maximum respiratory pressures, and capsaicin cough sensitivity testing. The registry lists the allocation as NA, masking as NONE, and model as SINGLE GROUP. Thus, the record does not describe randomized allocation, masking, or a parallel control arm.

The study summary frames a hypothesis about differences between people who have sustained brain injury and people who have not. That hypothesis is broader than the registered arm information: the described group consists of people with TBI, and no uninjured comparison group is described. As a result, the registered design supports description of measurements in the TBI group, but the record does not set out a direct comparison for assessing the stated between-population hypothesis.

The registry lists two outcome measures and zero analyses. The primary outcome is an average urge-to-cough rating after capsaicin administration on Day 1. The numerical outcome result, analysis population, and any analysis plan are not reported in the registry record. The record also does not report a sample-size justification or explain how enrollment was determined.

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 Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration, measured over Day 1.

The primary endpoint is the average urge to cough following administration of 200 Micro Mole capsaicin solution concentration, measured on Day 1. Participants first breathed normally through a facemask for 30 seconds to acclimate. They were then instructed to take a sharp breath in as nebulized capsaicin was administered by a dosimeter. After each aerosol presentation, participants rated their urge to cough using a modified Borg Rating Scale, where 1 means no urge to cough and 10 means maximum urge to cough. Participants had at least a one-minute rest between presentations and were offered water. The endpoint averages the ratings across all measurements.

This is a continuous measure: it records a graded rating rather than simply whether a cough occurred. The rating is used to describe participants’ reported urge to cough in response to the capsaicin procedure. Averaging across measurements gives one summary value for the endpoint as defined in the registry. The record does not report the number of presentations or the numerical average, and it does not report the variability of observed ratings.

In general, an urge-to-cough rating captures a participant’s reported sensation, not a direct measure of cough frequency or cough waveform. The study also lists cough and respiratory measures among its assessments, but the details and results for the other outcome measure are not reported in the registry record. No conclusion about the relationship between the urge rating and other measures can be drawn from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a continuous rating summarized by a mean. In general, a mean combines individual observations into a measure of central tendency. It can be useful when an outcome has ordered numerical values and the scientific question concerns an average response. The endpoint definition says that ratings from all measurements were averaged, but it does not state the number of measurements, the resulting mean, or the distribution of individual ratings. Those details are not reported in the registry record.

General statistical explanation: A standard error quantifies how much an estimated mean would vary across repeated samples under a statistical model. It describes uncertainty in the estimate, not the range of ratings among participants. A confidence interval uses an estimate and its uncertainty to express a range of values compatible with the data under specified assumptions. Neither a standard error nor a confidence interval for the endpoint is reported in the registry record, so the precision of the primary result cannot be assessed.

Design determines which questions an analysis can answer. This study is listed as SINGLE GROUP, with allocation NA and masking NONE. The arm information describes participants with TBI and does not describe an uninjured comparison group. Consequently, the design recorded does not provide an estimate of the difference between participants with TBI and participants without TBI. The summary’s stated hypothesis about such differences should be read as the motivation for the research, not as evidence that a between-group comparison was conducted.

The registry lists zero analyses. It does not report a model, a test, an adjustment strategy, or an inferential result for the primary endpoint. It also does not report whether the endpoint was analyzed using participant-level averages, another summary, or an approach accounting for repeated measurements. The endpoint description says an average across all measurements was performed, but does not give further statistical details. No unreported analysis method should be inferred from that wording.

General statistical explanation: Repeated observations from the same participant may be related to one another. When observations are correlated, treating each one as independent can understate uncertainty. Methods that account for within-participant correlation can be appropriate when repeated observations are analyzed individually. If observations are first reduced to a participant-level average, the analysis instead needs to account for variation among those participant averages. The registry does not say which approach was used beyond stating that an average across measurements was performed.

Over-dispersion is a general issue when observed variability exceeds what a chosen statistical model expects. When relevant, it can make standard errors from an overly restrictive model too small and confidence intervals too narrow. The endpoint is described as a mean of a continuous measure, and no distributional model or evidence of over-dispersion is reported in the registry record. It is therefore not possible to say whether over-dispersion was assessed or whether it affected an analysis.

The planning assumptions are distinct from the actual study design and results. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and relates the effect to a stated fraction of an observed effect. It is an illustration for planning, not an observed-power calculation and not evidence that this study enrolled two arms. The registry record does not report the trial’s own sample-size justification. With a single described group and enrollment of 4, the illustration should not be interpreted as a design feature or as evidence of the precision achieved.

Sample-size planning generally asks how many participants might be needed to detect an effect under specified assumptions. It depends on the outcome variability, target effect, analysis, allocation, and chosen error rates. A planning calculation does not show that the target effect occurred, nor does it establish whether an observed estimate is precise. The registry record does not give numerical planning results or enough information to reconstruct them, and no additional calculation can be supported by the recorded endpoint details.

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("Individuals With TBI")
n   <- c(4)
m   <- c(4.5)
sp  <- c(1.68)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Individuals With TBI  4  4.500  3.360  -0.847  9.847

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies one primary outcome: average urge to cough after administration of capsaicin on Day 1. The other outcome measure is not described in the registry record for this account. The registry record does not report a multiplicity strategy, such as an approach to account for testing more than one outcome. Without results or an analysis plan, it is not possible to assess how multiple outcomes were handled or whether any adjustment was used.

Zero analyses are listed. The registry record does not report a statistical analysis plan, prespecified contrasts, covariate adjustments, or interim analyses. Whether interim analyses were planned or conducted is not reported in the registry record. No inference about these choices can be made from the study’s completed status.

The record gives an enrollment of 4 but does not report the number of participants with an observed primary endpoint, the number included in an analysis, or the handling of missing observations. Missing-data methods, reasons for any unavailable measurements, and withdrawals are not reported in the registry record. The primary endpoint description states that ratings were averaged across measurements, but does not specify how incomplete measurement sequences would be handled.

The analysis population is also not reported in the registry record. It is not stated whether the endpoint summary, if calculated, would include everyone enrolled, only participants who completed the testing, or another group. Enrollment and study status alone cannot establish outcome completeness or the analysis denominator. These omissions limit evaluation of possible bias from missing data and prevent confirmation of how many participants contributed to any result.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 4 people with TBI at risk for serious adverse events and records 0 serious adverse events in that group. It also lists 4 at risk for other adverse events and records 0 other adverse events. These are the posted event counts for the single described group. No serious adverse event terms are listed.

These figures describe the entries in the registry record; they do not show how safety events were defined, how long participants were followed for safety, or how events were collected. Those details are not reported in the registry record. The record also does not say whether every enrolled participant completed all assessments or contributed to the safety follow-up.

Deaths are recorded as null. A null value is not a numerical count of zero; the number of deaths is not reported in the registry record. The event counts should therefore be read as the reported figures for the listed categories, not as a complete account of all possible safety information. With only the registry entries described, no broader conclusion about safety can be drawn.

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

The registry describes an assessment of urge to cough and other cough and respiratory measures among people with TBI. Its primary endpoint is an average rating following capsaicin administration on Day 1. The record supplies the measurement procedure and enrollment of 4, but does not report a numerical primary endpoint result. It therefore does not establish the average rating observed or how precisely that average was estimated.

The study summary proposes that people with brain injury may differ in cough waveform and respiratory measures from people without brain injury. However, the arm information describes only people with TBI, and no control group is described. The record therefore does not report a direct comparison between those populations. The hypothesis should not be treated as a finding.

The study is listed as completed, but completion status is not a substitute for posted outcome data. The registry lists two outcome measures and zero analyses. It does not report a statistical test, estimate, confidence interval, or analysis population. Consequently, the registered information does not support a claim about the magnitude, direction, or statistical uncertainty of an endpoint result.

The record also does not describe a therapeutic comparison. Its listed procedures are assessments, including capsaicin cough sensitivity testing and respiratory measures. The design does not establish whether a treatment changes symptoms or outcomes, and the information recorded does not support a clinical recommendation. In general, a measurement study can characterize responses in its enrolled group, but a comparison or causal claim requires appropriate design and analysis details that are not reported in the registry record.

The appropriate reading is narrow: the registry records a small, single-group assessment and defines a primary rating-based endpoint. It does not report the endpoint result or the comparison that the summary hypothesis references. Any interpretation beyond the study procedures, design, and recorded safety counts would require results or methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the difference between its motivating hypothesis and its registered group structure. The summary raises the possibility of differences between people with and without brain injury, while the arm description identifies only a TBI group. That distinction matters because a hypothesis about a contrast requires observations from the populations being contrasted, along with a suitable comparison. The registry does not describe such a comparison.

The primary endpoint also illustrates why outcome definitions and outcome results are separate pieces of evidence. The record provides a detailed procedure for eliciting and rating urge to cough, including a modified Borg scale and averaging across measurements. Yet it does not report the resulting average or its uncertainty. A clearly defined measure helps readers understand what was intended to be assessed; it cannot by itself show what the assessment found.

Enrollment was 4, and the registry lists zero analyses. These registry entries make the absence of reported estimates especially consequential for statistical interpretation: without a numerical result and analysis details, readers cannot assess either the observed response or its precision. The record does not report a sample-size justification, so the enrollment cannot be interpreted as having been selected to meet a stated precision or power target.

The record is also a reminder to distinguish planning illustrations from trial results. The stated planning assumptions refer to two-arm allocation and a normal approximation, but the registered study is single-group. Planning calculations may demonstrate how assumptions affect a hypothetical design; they do not transform the actual design, supply missing outcome data, or establish observed power.

For researchers, the key statistical lesson is to align the question, design, and analysis. A descriptive endpoint in one group can answer a different question from a between-group contrast. Clear reporting of outcome values, uncertainty, analysis populations, and missing-data handling is needed to judge what conclusions the study can support.

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 principal limitation for interpreting this record is that the primary endpoint result is not reported in the registry record. No mean, standard error, confidence interval, or statistical test is available. Although the endpoint procedure is described, the effect and its precision cannot be evaluated from the recorded information.

The study has one described group and enrollment of 4. No uninjured comparison arm is described, despite the summary’s hypothesis about differences between people with and without brain injury. The recorded design therefore does not report a direct estimate of that contrast. The single-group structure also means that findings from this group, if results were available, would not by themselves establish how measurements differ from those in another population.

The registry does not report the number of participants with complete primary outcome data, the analysis population, or how missing ratings were handled. It does not report the number of capsaicin presentations per participant, the distribution of ratings, or further details of the analysis beyond averaging measurements. These omissions restrict assessment of data completeness, within-participant variability, and the precision of any mean.

The record lists two outcome measures but does not describe the other measure in the registry record, and it reports zero analyses. Multiplicity handling, the statistical analysis plan, interim analyses, and the sample-size justification are not reported in the registry record. Safety follow-up duration and event definitions are also not reported. The status COMPLETED does not fill these reporting gaps or indicate which participants contributed data to each measure.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessment of Dystussia in Traumatic Brain Injury — NCT02240329.
• Registry record last updated 2015-10-28; status last verified 2015-09.
• Results first posted 2015-10-28.
• 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

NCT02240329, titled Assessment of Dystussia in Traumatic Brain Injury, is a completed EARLY PHASE1, single-group study sponsored by the University of Florida. The registry records enrollment of 4, a start date of 2013-03, and primary completion in 2015-06. The described group consists of people who sustained TBI during the previous five years. Allocation is listed as NA and masking as NONE.

Assessments include neuropsychological testing and measures of TBI severity, respiratory measures, and capsaicin cough sensitivity testing. The primary outcome is average urge to cough following 200 Micro Mole capsaicin solution concentration on Day 1, rated with a modified Borg scale. The registry lists two outcome measures and zero analyses. The numerical primary result, analysis population, and missing-data methods are not reported in the registry record.

The registry records 0 serious adverse events and 0 other adverse events among 4 at risk in the TBI group. Deaths are not reported as a numerical count. The study summary states a hypothesis about differences between people with and without brain injury, but no comparison group is described.