Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction (NCT01053507), a randomized phase 4 study. The primary outcome is Headache Days.

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, double-masked, parallel-group study of Treximet and matching placebo. The registry lists enrollment of 23 and describes a three-visit process. At Visit 1, participants began a 30-day period using their usual medication and documenting headache symptoms and therapy in a diary. At Visit 2, they were randomized to Treximet or placebo, then completed a further 30-day treatment period with daily diary entries. The summary says they exited at Visit 3 after that period.

The registry lists the study start as 2010-05 and primary completion as 2012-11. Its status is terminated. The reason for termination and any effect that termination had on recruitment, follow-up, or the planned analyses are not reported in the registry record. Although the record lists enrollment of 23, the primary endpoint results include 7 participants in the Treximet arm and 10 in the placebo arm. These are the analysis counts for the posted endpoint, not a statement about how every enrolled participant was handled.

Randomization is described as occurring “like the flip of a coin,” but details such as sequence generation, allocation concealment, stratification, and implementation are not reported in the registry record. The record identifies the study as double-masked but does not say which study personnel were masked. The parallel design means the record presents separate groups receiving Treximet or placebo, rather than describing a crossover. No additional protocol details or design rationale are reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis population only includes subjects that provided data at both time points (Day 0 and Day 30).

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 Headache Days, measured over Day 0, Day 30.

The primary endpoint is the change in the number of headache days, expressed as a mean with standard deviation. The stated timeframe compares Day 0 with Day 30, and the description says the change was assessed in the Treximet arm versus the placebo arm. A headache-day count is a continuous measure when summarized across participants as a mean, even though an individual participant’s count is discrete. It can describe the frequency of headache over the assessment period in a way that is directly connected to the study question.

Change measures use each participant’s observations at two time points to describe movement over the study period. Comparing changes across randomized groups can help distinguish a pattern during treatment from a pattern also seen in the comparison group. This is a general explanation of the endpoint’s statistical role; the registry record does not give a more detailed definition of how the change was calculated, such as the subtraction order or the diary rules used to count a headache day.

The primary analysis population required data at both Day 0 and Day 30. That makes the posted mean a summary of participants with both observations, rather than necessarily all enrolled participants. The record reports the arm means and standard deviations but no confidence intervals and no estimable two-arm comparison. Consequently, the endpoint results allow a descriptive reading of the two arm summaries, while the uncertainty around their difference is not available from the posted analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous in the registry’s statistical description: it is the mean change in headache days. A mean condenses a set of participant-level changes into one central summary. It is useful for describing the average pattern, but it does not show whether most participants had similar changes or whether a small number of unusually large changes influenced the summary. The posted standard deviation gives information about spread, but not the full distribution.

What does the standard deviation describe?

In general, a standard deviation summarizes how dispersed observations are around their mean. A larger standard deviation indicates more variability among the observations represented by that summary. It is not a measure of the uncertainty in the estimated mean, and it is not the same as a confidence interval. To estimate the uncertainty in a mean or in a difference between means, the analysis also needs to account for the number of observations and the statistical method used. The registry gives arm counts and standard deviations here, but does not post confidence intervals or an inferential comparison.

The primary outcome description refers to a change between Day 0 and Day 30. In general, analyzing change can account for the starting measurement in a direct way, but the meaning of a signed change depends on the stated subtraction convention. The subtraction order is not reported in the registry record. It is therefore safest to retain the posted values as signed changes, rather than reinterpret their signs as a specific direction of improvement or worsening. The diary definition of a headache day is also not reported in the registry record.

Why is the comparison more than a comparison of means?

In general, a randomized two-arm study asks about the contrast between groups, not just whether each group’s mean differs from zero. The observed arm means are summaries within each group. A formal comparison estimates the difference between those summaries, with uncertainty, and may use an analysis specified in the study plan. Here, a two-arm result was not available or estimable in the posted results. The registry does not identify a test, model, covariate adjustment, or confidence-interval method for the primary endpoint. No such method should be inferred from the descriptive summaries.

Confidence intervals, in general, express uncertainty around an estimate under the assumptions of the method used to calculate them. A narrower interval usually indicates greater precision, while a wider interval indicates less precision. Because no confidence interval is posted for the arm contrast, the precision of a comparative effect cannot be read from this record. The standard deviations cannot substitute for that missing interval. The posted arm summaries can still be described, but they do not supply the full inferential result.

What can the sample-size illustration tell us?

The sample-size section is a planning illustration based on an observed effect, with an assumed two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, a planning calculation asks how many participants might be needed to detect a specified effect under stated assumptions. It does not describe how many participants were actually analyzed, and it is not observed power. The calculation is not the trial’s own design justification. The registry record does not report the original sample-size rationale or establish that the trial was planned using the assumptions in the illustration.

Planning illustrations also depend on what effect is selected and on assumptions about variability and analysis. An effect drawn from a small observed dataset may be uncertain, so such illustrations should be treated as conditional scenarios rather than evidence that the trial had a particular probability of finding a result. The record does not post an inferential two-arm result for this endpoint. Any planning calculation should therefore be kept conceptually separate from the posted clinical outcome summaries.

Why does variability matter?

In general, greater variability makes it harder to estimate a group mean or a between-group contrast precisely, all else being equal. When data are more dispersed, a mean may represent participants less uniformly. If observations are skewed or include influential values, a mean and standard deviation may not capture the features most relevant to interpretation. The registry record does not provide distributions or enough detail to assess those possibilities. Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes: standard errors and tests can then be misleading if the model does not accommodate the extra variation. The record does not state that over-dispersion was assessed or that a model requiring such an assessment was used.

Analyses of change scores can also be affected by the relationship between baseline and follow-up values. General methods may model follow-up while accounting for baseline, or summarize within-participant change and compare those changes. The registry describes a change endpoint but does not report the analysis method. It would be inappropriate to claim that a particular approach was used or to compare the properties of approaches as though the protocol had selected one.

Finally, an analysis limited to participants with both time points depends on who has complete observations. If missingness is related to the outcome or to participant characteristics, a complete-case summary may not represent the full randomized groups. This is a general limitation, not a finding that missingness was biased in this trial. The registry does not report why endpoint data were unavailable, whether other missing-data methods were considered, or whether a sensitivity analysis was conducted. Those omissions constrain what can be concluded from the posted endpoint summaries.

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("Treximet", "Placebo")
n   <- c(7, 10)
m   <- c(-3, -0.3)
sp  <- c(7.6, 5.3)
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  Treximet  7  -3.000  7.600  -10.029  4.029
CARM  Placebo  10  -0.300  5.300  -4.091  3.491

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint as headache days and names three secondary outcomes: the Mental Efficiency Workload Test (MEWT) Performance Index, the Headache Impact Test-6 (HIT-6) Score, and the Migraine Specific Quality of Life Questionnaire (MSQ). It also indicates five outcome measures overall. Results for the secondary outcomes and details for any other outcome measure are not reported in the registry record. The posted primary endpoint is therefore the focus; the record does not allow a broader account of the outcome findings.

When a study evaluates multiple outcomes, time points, or comparisons, the chance of finding an apparently notable result by chance can increase. Statistical plans may address this multiplicity through a prespecified hierarchy, adjustment, or other strategy. This is a general explanation, not a statement about what this trial did. A multiplicity plan, adjustment method, or rationale for handling the listed outcomes is not reported in the registry record. No claim about control of multiplicity can be made from the listed summaries.

The primary analysis population included only participants who contributed data at both Day 0 and Day 30. This is a complete-case restriction for the endpoint as described. The registry does not report how many participants lacked one or both measurements, why data were absent, or whether missingness differed by arm. It also does not describe imputation, a missing-data model, sensitivity analyses, or an alternative population such as all randomized participants. The effect of missing observations on the reported means cannot be assessed from this record.

The record lists enrollment of 23, while the primary endpoint summaries have arm counts of 7 and 10. The record does not provide a participant flow accounting for the difference between enrollment and endpoint analysis. It also lists zero posted analyses, so the analysis methods and any prespecified-versus-posted outcome distinctions are not available. These gaps do not prove that a particular method was or was not used; those details are simply not reported in the registry record.

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.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events in groups at risk of 11 participants for Treximet and 12 for placebo. It reports zero serious adverse events in each group. No serious adverse event terms are listed. Death counts are not reported in the registry record. These entries describe what is posted; they should not be read as a comprehensive account of every possible safety outcome.

The record also lists other adverse events for 7 participants at risk of 11 in the Treximet arm, and for 11 participants at risk of 12 in the placebo arm. These are participant counts, not a measure of event severity or duration. The registry does not give the event terms in this summary, so the types of other events cannot be described. Nor does this record state whether these events were considered related to study medication.

Adverse-event counts depend on the population observed, the definitions used, and the collection and reporting procedures. Details of those procedures are not reported in the registry record. The at-risk counts differ from the primary endpoint analysis counts, and the registry does not explain the relationship between those populations. The counts should therefore be read separately from the headache-day analysis and should not be used to infer comparative rates or an overall safety conclusion.

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

The posted results show mean headache-day changes of -3.0 days in the Treximet arm and -0.3 days in the placebo arm among participants with data at both Day 0 and Day 30. The standard deviations were 7.6 and 5.3, respectively. Those values describe the endpoint summaries in the analyzed groups. They do not, by themselves, quantify a reliable between-arm effect or its uncertainty.

The registry does not provide an estimable two-arm comparison for this continuous endpoint, a confidence interval, or a p-value. It therefore does not establish how precisely the arm contrast was estimated. It also does not report the reasons for termination or missing endpoint data, the analysis method, or a sample-size justification. These limitations mean that the posted summaries cannot answer every question a reader might have about the trial’s design and results.

The results also do not establish what would have happened in participants who did not contribute data at both time points, or whether the analyzed participants represent all randomized participants. The registry does not report results for the named secondary outcomes, so no conclusions about those measures can be drawn from this record. The safety entries list serious and other adverse-event counts, but do not provide the detail needed to characterize event types or establish a comparative safety profile.

In general, a randomized comparison is interpreted using the estimated between-group contrast, its uncertainty, the analysis population, and the study’s conduct. Here, the available information supports a descriptive account of the two arm means and spreads, not a definitive causal or clinical conclusion. The numbers do not show on their own whether any difference arose from treatment, random variation, incomplete observations, or other influences. This is a statistical reading of the registry record, not medical advice and not a claim that either treatment is effective or ineffective.

14. Why This Trial Matters Statistically

This trial is statistically notable because the registry presents arm-level summaries for its primary outcome but not an estimable two-arm comparison. That distinction is central in randomized studies. The research question concerns the relative pattern between Treximet and placebo, whereas an arm mean alone describes only the participants summarized in that group. Without an estimate and uncertainty for the contrast, the posted result has limited inferential reach.

The primary analysis population also illustrates why denominators matter. The registry lists enrollment of 23, yet the headache-day summaries use 7 participants in the Treximet arm and 10 in the placebo arm, defined by availability of both time points. The record does not explain the participant flow or missingness. Readers need to distinguish enrollment, participants at risk for adverse events, and participants contributing to a specific endpoint rather than treating these counts as interchangeable.

Termination adds context but does not explain itself. The study status is terminated, while the reason and its implications are not reported in the registry record. Without that information, readers cannot determine whether termination affected the planned sample, duration, analysis, or reporting. This is a reason to be careful about interpretation, not a basis for assuming a particular problem.

The record also names secondary measures but does not post their results or a multiplicity strategy. This highlights the importance of complete outcome reporting and an accessible analysis plan. The accompanying sample-size material is a planning illustration, not evidence of the trial’s design rationale or observed power. Taken together, the record demonstrates how descriptive results, missing analysis details, and incomplete outcome information shape the conclusions a statistical reader can responsibly draw.

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 trial-specific limitations arise from the record. The study is marked terminated, but the reason for termination is not reported in the registry record. Enrollment is listed as 23, while the primary endpoint summaries include 7 participants in the Treximet arm and 10 in the placebo arm. The record does not provide a participant flow diagram or explain why some enrolled participants are absent from the endpoint analysis.

The primary outcome population required observations at both Day 0 and Day 30. The record does not describe missing-data methods, imputation, sensitivity analyses, or the characteristics of participants without both observations. It is therefore not possible to assess whether the complete-case summaries may differ from results in the full randomized groups.

The two arm means and standard deviations are posted, but the two-arm comparison is not estimable in the record. A confidence interval, p-value, adjusted estimate, and statistical model are not reported. The change-score convention and operational definition of a headache day are also not reported in the registry record. Those details would help make the signed values and endpoint construction more transparent.

The registry lists secondary outcomes, but their results are not reported, and it does not describe any multiplicity strategy. It also does not report the original sample-size justification, the randomization implementation details, or the reason the study ended. Safety information is summarized as counts, with no listed serious-event terms; death counts and further details about other adverse events are not reported in the registry record. These limitations restrict interpretation of the posted summaries without showing that any specific bias or adverse outcome occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction — NCT01053507.
• Registry record last updated 2020-07-29; status last verified 2020-07.
• Results first posted 2014-03-10.
• 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

This registry record describes a Phase 4, randomized, double-masked, parallel-group trial of Treximet versus matching placebo for post-traumatic headache associated with cognitive dysfunction. Enrollment was 23; the study status is terminated. The primary endpoint was change in headache days from Day 0 to Day 30 among participants with data at both time points.

The posted mean changes were -3.0 days for Treximet and -0.3 days for placebo, with standard deviations of 7.6 and 5.3. The analysis counts were 7 and 10, respectively. The registry does not provide an estimable two-arm comparison or confidence interval. It lists three secondary outcomes but does not report their results. Serious adverse events were listed as zero in each group; other adverse-event counts were also posted. Reasons for termination, missing endpoint data, and key analysis details are not reported in the registry record.