Does Treximet Improve Productivity and Patient Satisfaction Due to Sustained Response and Consistency of Response?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Does Treximet Improve Productivity and Patient Satisfaction Due to Sustained Response and Consistency of Response? (NCT01086358), a randomized phase 4 study. The primary outcome is Workplace Productivity and Activity Impairment Scale (WPAI)..

2. Clinical Question

The study addressed whether work and activity time lost after a treated migraine attack differed when participants used Treximet rather than their usual prescribed triptan. The registry describes a randomized, open-label, two-arm crossover study: participants began with one treatment and then took the other in a second phase. Each treatment was used for 3 workday migraine attacks, and participants completed questionnaires after treating each migraine.

The primary outcome was a variant of the Work Productivity and Activity Impairment Scale. It combined lost workplace productivity with lost non-workplace activity time and expressed the result in hours. Higher scores indicate greater productivity impact. The registry’s primary efficacy dataset was limited to the 37 patients who completed both phases and all study visits; the analysis used the last observed headache.

This is a question about reported productivity impairment in the analyzed participants, not about migraine frequency or a direct measure of treatment efficacy on headache symptoms. The registry also lists secondary outcomes concerning lost workplace productivity, lost activity time, and a favorable response on Migraine-ACT. Their detailed results are not reported in the registry record in the registry record described for this analysis.

3. Trial Design

The registry describes a Phase 4, randomized, open-label, single-center, two-arm crossover study sponsored by The Cleveland Clinic. Its title frames the comparison as subject productivity improvement and satisfaction with migraine treatment using Treximet versus usual triptan. The study status is completed. The registry lists an enrollment of 60, while the primary efficacy analysis included 37 patients who completed both study phases and all visits.

In a crossover design, participants receive both treatments in sequence, rather than remaining in only one treatment group throughout the study. Participants began with either their prescribed triptan or Treximet, and then entered the other treatment phase. The study description says that participants used each treatment for 3 workday migraine attacks and completed questionnaires after each treated migraine. The allocation sequence was randomized; masking was none, so treatment was open-label.

The outcome timeframe is 6 months. The primary analysis was based on the last observed headache for each participant in the group that completed both phases. The registry describes the unit of analysis as hours lost, with total lost productivity defined as lost work productivity plus lost non-workplace activity time. It gives observed attack ranges of 0-10.5 hours for lost work productivity and 0 to 8.95 hours for lost non-workplace activity time; the total range depends on attack length.

The crossover structure is relevant to interpretation because participants serve as their own treatment comparators across phases. However, the registry record does not report the treatment sequence details beyond which treatment each arm began with, nor does it describe period effects, carryover effects, washout procedures, or the precise model structure beyond identifying a mixed models analysis. Those design and modeling details should not be inferred.

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: This study had no wash-out or run-in phase.

First Intervention

Reasons for not completing this period:

Second Intervention

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This includes all patients that completed all study visits are included in this efficacy 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 Workplace Productivity and Activity Impairment Scale (WPAI)., measured over 6 months.

The primary endpoint was lost productivity measured with a variant of the Work Productivity and Activity Impairment Scale. The score was reported in hours and combined lost workplace productivity with lost non-workplace activity time. The registry states that higher scores mean a greater impact on productivity. For the analyzed headache, the score therefore represents time away from work productivity and other activities attributed to the migraine episode.

Productivity is relevant to this study’s stated question because the trial concerned workday migraine attacks and the effects of treatment on participants’ ability to work and carry out activities. Combining workplace and non-workplace time gives a broader measure of the reported time impact than workplace time alone. The registry separately lists lost workplace productivity and lost activity time among secondary outcomes.

The range of possible hours depends on attack length, according to the registry. Among all observed attacks, lost work productivity ranged from 0-10.5 hours and lost non-workplace activity time ranged from 0 to 8.95 hours. These are descriptive ranges, not treatment-effect estimates. The primary comparison concerns mean hours lost, with a 95% confidence interval reported for each arm and for the model-based difference.

The primary efficacy analysis included participants who completed all study visits and both phases, and used the last observed headache. That definition matters: the result concerns this selected analysis population and the specified headache observation, rather than every enrolled participant or every attack recorded during the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported primary comparison uses a continuous outcome: lost productivity measured in hours. For a continuous measure, an arm mean describes the average value in the analyzed group. The reported mean values are 4.15 hours for usual prescribed triptan and 2.44 hours for Treximet. These means summarize the groups; they do not imply that every participant lost that amount of time.

What does the confidence interval communicate?

A confidence interval communicates uncertainty around an estimated quantity under the statistical model and its assumptions. For the arm means, the registry reports 95% confidence intervals of 2.93 to 5.36 and 1.23 to 3.65. For the mixed-model mean difference in final values, it reports a 95% confidence interval from -2.92 to -0.49. A narrower interval generally indicates greater precision than a wider interval, though precision is not the same as clinical importance.

A confidence interval is not a range containing a fixed share of individual patient outcomes. It also is not a statement that there is a specified probability that the true value lies within the particular interval after the data have been observed. Rather, it is a procedure for expressing the uncertainty of estimation under repeated use of the model and its assumptions. The interval should be interpreted together with the study design, the outcome definition, and the population analyzed.

How should the p-value be read?

The reported p-value is 0.007. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and model. It does not measure the probability that a treatment is effective, and it does not measure the magnitude of an effect. The p-value depends on the analysis assumptions and does not account automatically for every possible source of bias or uncertainty.

The registry identifies the method as a mixed models analysis and the parameter as mean difference in final values. Mixed models are a general family of methods that can represent correlated observations and account for modeled sources of variation. Such methods can be useful when observations are not independent, as may occur when the same participant contributes information under both treatments. The precise model terms, covariance structure, and handling of period or sequence are not reported in the registry record, so the exact role of those features cannot be established from the registry description.

Why does the crossover design matter statistically?

In a crossover study, treatment comparisons can use information from the same participant under both treatments. Because measurements from one participant tend to be related, an analysis should account for that correlation when appropriate. Mixed models are one general approach to modeling correlated data, but the registry’s short method label does not identify which correlation structure or specific adjustment was used.

Crossover results can also be affected by time-related changes, treatment sequence, or effects that persist from one phase into another. These are general design considerations, not findings about this trial. The registry record does not report whether such effects were assessed or how they were handled. The open-label design also means participants were not masked to treatment, which can matter when outcomes are collected through questionnaires and may be influenced by expectations or reporting behavior.

What does the sample-size illustration mean?

The planning illustration is based on the observed effect and stated assumptions: a two-sided significance level of 0.05, equal allocation, and a normal approximation. Its purpose is to illustrate planning under hypothetical effects defined as fractions of the observed effect. Such figures are planning illustrations, not evidence of the study’s original design rationale, and not observed power. The registry record does not report the trial’s sample-size justification. Any original assumptions or calculations should therefore not be inferred from a retrospective illustration.

In general, planning calculations depend on assumptions about the effect to detect, variability, allocation, and testing approach. If those assumptions differ from the actual study or the effect used is estimated from the study data, the illustration should not be treated as an independent confirmation of the result. No specific sample-size values are stated in the registry record described for this analysis.

Why distinguish statistical evidence from practical importance?

Statistical evidence and practical importance answer different questions. The p-value and confidence interval describe evidence and uncertainty under a model. They do not specify what size of change would matter to participants, employers, or clinicians. The registry record does not report a threshold for a clinically meaningful productivity difference. Without such a threshold, the estimated difference should be described in hours and with its uncertainty, rather than classified as important or unimportant.

Likewise, the means and contrast do not reveal how outcomes were distributed across participants. A group mean can coexist with substantial variation among individuals. The reported confidence intervals concern estimates, not the range of individual responses. These distinctions help keep the interpretation tied to the particular statistical quantities the registry reports.

10. Analyses Reported by the Sponsor

The registry reports a mixed models analysis of mean difference in final values: -1.71 hours, with a 95% confidence interval from -2.92 to -0.49 and p = 0.007. This is the sponsor-reported comparison identified in the registry record. The arm means are 4.15 hours for usual prescribed triptan and 2.44 hours for Treximet, consistent in direction with a lower observed mean for Treximet.

The registry record does not report a separate unadjusted recalculation of the comparison in the registry record described for this analysis, so a numerical contrast from such a recalculation cannot be compared with the mixed-model estimate. The mixed-model result should not be replaced by a calculation from the arm means: the registry identifies a model-based analysis, and its exact model specification is not reported. The registry record also does not provide enough detail to reconstruct that model.

No discrepancy between the sponsor analysis and a recalculation is flagged in the record. The appropriate interpretation is therefore to present the sponsor’s reported model result as the inferential comparison and the arm means as descriptive context. Neither should be extended beyond the completer population and endpoint that the registry specifies.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary productivity endpoint and three secondary outcomes: lost workplace productivity, lost activity time, and favorable response on Migraine-ACT. It also records four outcome measures and four analyses. The detailed statistical results for the secondary outcomes are not reported in the registry record. The primary endpoint and secondary outcomes concern related but distinct measures, and the primary estimate should not be taken as a result for all of them.

When multiple outcomes or repeated statistical tests are considered, the chance of obtaining at least one apparently notable finding can increase. General approaches to this issue include prespecifying a primary outcome, controlling a family-wise error rate, or treating secondary analyses as exploratory. The registry record does not report whether a multiplicity adjustment was used, how the outcomes were ordered for testing, or whether any outcome hierarchy was prespecified. The reported p-value should therefore be understood as the p-value attached to the stated primary mixed-model comparison, not as evidence that multiplicity was addressed.

The primary efficacy analysis included 37 patients who completed all study visits and both phases, and used the last observed headache. The record reports enrollment of 60. It does not report a detailed flow of participants between enrollment, treatment phases, completion, and analysis, or the reasons some enrolled participants were not included in the primary efficacy dataset. It also does not report the methods used to handle missing observations or whether sensitivity analyses were conducted.

Restricting analysis to completers can affect interpretation if completion is related to treatment experience or outcome. That is a general concern, not a claim about why participants were absent from this analysis. The registry description does not establish whether the analysis population was defined before the results were known or whether other analysis populations were examined.

The phrase last observed headache identifies the observation used for the efficacy analysis, but the record does not describe the timing of that headache for each participant or how multiple possible observations were selected in detail. Interim analyses, stopping rules, and a statistical analysis plan are not reported in the registry record. Their absence from the record should not be filled by assumptions.

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.

Most frequent non-serious adverse event terms

The safety figures list 45 participants at risk in each group. Serious adverse events affected 0 participants in the usual prescribed triptan group and 0 in the Treximet group. The registry lists no deaths in either group. These are the reported serious-event counts, not proof that no serious event could occur or that the treatments have identical safety profiles.

For other, non-serious adverse events, the registry reports 18 affected participants in the usual prescribed triptan group and 15 in the Treximet group, with 45 at risk in each. These counts describe participants with at least one reported event as represented in the record; they do not give the total number of events or their severity, timing, or duration. The registry does not provide serious adverse event terms in the record.

Safety counts should be read separately from the productivity outcome. The 45 participants at risk in the safety listing are not the same as the 37 completers in the primary efficacy analysis, and the registry does not explain the difference between these analysis populations. The figures alone do not establish comparative safety, particularly without further detail about event definitions, observation time, exposure, and statistical uncertainty. They should not be used as medical advice or as a basis for choosing a treatment.

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

The posted primary result is a comparison of mean hours of lost productivity for a specific analysis population in a randomized, open-label crossover study. The arm means were 4.15 hours for usual prescribed triptan and 2.44 hours for Treximet. The mixed-model estimate was -1.71 hours, with a 95% confidence interval from -2.92 to -0.49 and p = 0.007. The direction of the reported arm means and contrast is consistent with lower mean lost productivity for Treximet in this analysis.

This finding does not establish that every participant experienced less lost time with Treximet. Group averages do not describe the individual distribution, and the reported estimate does not predict an individual’s outcome. The confidence interval expresses uncertainty in the estimated mean contrast under the model; it does not show the range of outcomes participants experienced.

The result is limited to the endpoint defined as workplace productivity plus non-workplace activity time, measured in hours, and to the 37 participants who completed both phases and all study visits. It used the last observed headache. It does not directly measure headache relief, migraine recurrence, treatment satisfaction, or broader work performance beyond the stated scale. Although satisfaction appears in the study title, the registry entries do not provide a satisfaction result.

The trial was open-label, and the endpoint was based on questionnaires. Expectations and reporting behavior are general considerations for open-label questionnaire outcomes, but the record does not show whether or how they affected the estimates. The registry also does not report the model details needed to assess every assumption, or how missing observations were handled.

Statistical evidence is not the same as clinical importance. The registry does not report a threshold for a meaningful difference in productivity hours, so the result cannot be labeled clinically important from these figures alone. The primary result also does not answer the safety question; the safety counts are reported separately and require cautious interpretation.

Finally, the result should not be generalized beyond the trial context without considering its single-center setting, selected completer analysis, open-label design, and specified workday attacks. The posted data describe the observed comparison, not a universal effect across all people with migraine, work settings, or treatment patterns.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its crossover structure compares both treatments within the same participants. In general, within-participant comparisons can reduce the influence of stable differences between people, since each participant contributes experience under both treatment conditions. At the same time, this structure creates statistical dependencies that an analysis may need to model. The registry identifies a mixed models analysis, but does not report enough detail to determine exactly how it represented participant-level correlation or other features of the crossover.

The endpoint also illustrates the difference between a clinical symptom and a functional outcome. The primary measure is lost time attributed to a migraine attack, combining workplace and non-workplace activity time. Its units make the result interpretable as hours, while the confidence interval communicates that the mean difference is estimated with uncertainty. The record does not specify a threshold for meaningful change, keeping the statistical finding distinct from a judgment about practical importance.

Another important issue is the analysis population. Enrollment was 60, while the primary efficacy analysis included 37 patients who completed both phases and all study visits. This highlights why population definitions and participant flow matter when interpreting a result: a model estimate for completers is not automatically an estimate for everyone enrolled. The registry does not describe reasons for non-completion or missing-data procedures, so the influence of those factors cannot be determined from the record.

Finally, the reported p-value and confidence interval are useful but do not resolve every question. The open-label design, questionnaire-based endpoint, unreported modeling details, and absent multiplicity information all shape how much can be concluded. Reading the estimate alongside its design and reporting limits is more informative than treating statistical significance as a complete answer.

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 result comes from a single-center study, and the registry record does not describe additional sites or settings. Its open-label design means participants knew which treatment they were using. Because the primary measure was based on questionnaires, treatment awareness is relevant as a general potential influence on reporting, although the registry does not establish that it affected the result.

The analysis population was restricted to the 37 patients who completed both phases and all study visits, while the registry lists enrollment of 60. The record does not explain this difference, provide a full participant flow, or describe reasons for non-completion. It also does not report how missing outcome data were handled or whether the primary analysis was accompanied by sensitivity analyses. These omissions limit assessment of how representative the analyzed participants are of all enrolled participants.

The registry identifies a mixed models analysis but does not report the detailed model specification. It does not state how period, sequence, carryover, or within-participant correlation were handled, nor does it report tests or evaluations concerning those features. These are relevant considerations for a crossover design, but no conclusion about their presence or impact can be drawn from the available record.

The primary endpoint uses the last observed headache and combines lost work productivity with lost non-workplace activity time. Details about the selection and timing of that headache are not reported. The endpoint is specific to the measured productivity construct and does not substitute for results on migraine symptoms, satisfaction, or the secondary measures. Detailed secondary outcome results are not reported in the registry record.

The record does not report the original sample-size justification, a prespecified meaningful-difference threshold, multiplicity procedures, interim analyses, or a statistical analysis plan. The results should therefore be interpreted as the reported analysis rather than as a complete account of all planned or conducted analyses. These limitations do not negate the posted estimate; they define the boundaries of what can be inferred from the registry description.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Does Treximet Improve Productivity and Patient Satisfaction Due to Sustained Response and Consistency of Response? — NCT01086358.
• Registry record last updated 2018-05-01; status last verified 2018-03.
• Results first posted 2018-05-01.
• 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, Phase 4, randomized, open-label, single-center crossover study sponsored by The Cleveland Clinic. Enrollment was 60. Participants treated 3 workday migraine attacks with their usual prescribed triptan and 3 with Treximet, in randomized sequence, and completed questionnaires after treatment.

The primary endpoint was mean hours of lost productivity, combining workplace productivity and non-workplace activity time. The primary efficacy analysis included 37 participants who completed both phases and all study visits and used the last observed headache. The reported arm means were 4.15 hours for usual prescribed triptan and 2.44 hours for Treximet. The mixed-model mean difference in final values was -1.71 hours, with a 95% confidence interval from -2.92 to -0.49 and p = 0.007.

The record lists secondary outcomes concerning lost workplace productivity, lost activity time, and favorable Migraine-ACT response. Detailed results and several methodological details, including missing-data handling and the precise model specification, are not reported in the registry record.