Aspirin for Treatment of Multiple Sclerosis-Related Fatigue: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aspirin for Treatment of Multiple Sclerosis-Related Fatigue (NCT00467584), a randomized phase 3 study. The primary outcome is Modified Fatigue Impact Scale Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study sponsored by Mayo Clinic. It compared high-dose aspirin, low-dose aspirin, and placebo for multiple sclerosis-related fatigue. Randomization means treatment assignment was intended to be determined by chance, which can help balance participant characteristics across groups. The registry record does not describe the randomization procedure or whether allocation was concealed.

The double-blind designation indicates that the study was recorded as blinded, but the registry record does not identify which groups of people were masked or describe how masking was maintained. Matching placebo tablets were used, according to the arm description. The parallel design means participants were assigned to a treatment group rather than described as switching between treatments.

The study began in 2007-07, and primary completion was recorded as 2013-09. Its status is listed as terminated. The reason for termination and whether it was related to recruitment, safety, resources, or another consideration are not reported in the registry record. A termination status alone does not establish why a study ended or whether its planned analyses were completed.

The registry records 62 randomized patients and says that 52 were included in the analysis after six did not receive intervention and an additional four discontinued without follow-up data. It does not give the number randomized to each treatment arm in the primary-outcome description. The separate adverse-event listings give at-risk counts by group, but those listings do not replace a full account of allocation and outcome follow-up.

The primary measure was the Modified Fatigue Impact Scale score at baseline and 8 weeks. The record also says the week 4 score was used for a participant who withdrew before week 8. Numerical primary-outcome results and statistical analyses are absent from the registry record, so the relative results across the three groups cannot be described.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 62 patients were randomized; of these, 6 did not receive the intervention and an additional 4 discontinued without providing followup data. Therefore 52 were included in the analysis. The Wk 4 MFIS score was used if the subject withdrew prior to Wk 8. 1 subject each in the High Dose and Placebo groups provided MFIS data at Wk 4 but not Wk 8.

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 Modified Fatigue Impact Scale Score, measured over Baseline, 8 weeks.

The primary endpoint was the Modified Fatigue Impact Scale score, reported in units on a scale. The instrument consists of 21 statements about ways fatigue may affect functioning. Participants answered with reference to the prior 4 week period, using response options from 0, Never, to 4, Almost always. The answers contribute to a total score ranging from 0, indicating no fatigue impact, to 84, indicating almost always impacted by fatigue.

The score is relevant to the study question because it captures the reported effect of fatigue on functioning, rather than treating fatigue only as a general label. By the scale’s stated direction, lower scores mean less fatigue-related impact and higher scores mean greater impact. That direction is important when interpreting any mean change or treatment-group contrast: the meaning of a higher or lower value follows the scale definition.

The registry lists the measure as a mean with standard deviation and gives baseline and 8 weeks as the timeframe. It also states that a week 4 score was used when a participant withdrew before week 8. Numerical means, standard deviations, changes from baseline, and group comparisons are not reported in the registry record. The endpoint description therefore establishes what the scale measures and how to read its direction, but not what the study observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical scale score rather than a count of participants in a category. The registry identifies the summary measure as a mean and the measure of dispersion as a standard deviation. A mean describes the central value of a set of scores. A standard deviation describes how spread out individual scores are around that mean. They answer different questions: the mean describes the group’s average score, while the standard deviation describes variability among scores.

For a continuous outcome, a treatment comparison can be expressed as a difference between group means, or as a difference in change from baseline, depending on the analysis plan. These are general approaches, not claims about the analysis used in this study. The registry record does not report a statistical analysis plan or numerical results, so it does not establish which comparison was conducted, whether baseline scores were adjusted for, or how repeated measurements were modeled.

Baseline measurement can help describe the groups before treatment and can be used in some analyses to account for initial score differences. A follow-up score addresses status at the later assessment, while a change score describes movement from baseline. Those approaches can produce estimates with different interpretations. The record names baseline and 8 weeks as the timeframe but does not report group means at either assessment or explain whether the primary contrast was based on follow-up values or change.

A confidence interval is a statistical way of expressing uncertainty around an estimated effect. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. It is useful to interpret the interval’s range and direction, not merely whether it includes a threshold. No confidence interval or treatment-effect estimate for the primary outcome is reported in the registry record, so precision cannot be assessed from the reported primary results.

A p-value is calculated under a specified null hypothesis and analysis model. It does not quantify the probability that a treatment works, and it does not describe the size or practical importance of an effect. The registry lists zero analyses and does not report a primary-outcome p-value. Accordingly, there is no basis in the registry record for describing statistical significance.

The study has three treatment groups. In general, comparisons among several groups create a multiplicity issue: if many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the testing strategy accounts for that. A prespecified primary contrast, a testing hierarchy, or an adjustment procedure can address this concern in different ways. The registry record does not report which comparisons were planned, whether any adjustment was used, or whether interim analyses occurred. These details must not be inferred from the number of arms alone.

Missing outcome data also affect interpretation. If participants with unavailable follow-up differ systematically from those measured, an analysis limited to observed scores may not represent all randomized participants. General methods for addressing missingness include model-based approaches and sensitivity analyses, but the appropriate method depends on assumptions about why values are missing. The record states that six randomized patients did not receive intervention and four more discontinued without follow-up data. It says that a week 4 MFIS score was used if a participant withdrew before week 8. It does not describe additional imputation, sensitivity analyses, or assumptions about missingness.

The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is not the trial’s original design justification and is not observed power. It estimates a planning requirement under stated assumptions; it does not show the probability that the completed study detected an effect. The registry record does not report the original sample-size justification or provide numerical results for the illustration in the registry record for this analysis.

Over-dispersion is a general concern for count outcomes when variation exceeds what a chosen count model expects. It can lead to uncertainty estimates that are too small if ignored. The primary endpoint in this study is a continuous scale score, not a count outcome, so a count-model over-dispersion explanation does not determine how to analyze this endpoint. The key missing information for interpreting the registered primary outcome remains the absent numerical scores and treatment comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the Modified Fatigue Impact Scale, but also notes that the outcome has several categories or time points and was not reduced to one comparison. The measure is described at baseline and 8 weeks, with a week 4 value used for a participant who withdrew before week 8. An outcome measure and a statistical comparison are not the same thing: a single measure may yield multiple time-specific results or treatment contrasts. The registry record does not state which comparisons were prespecified as primary or how multiplicity was handled.

Because there are three study groups, a complete analysis could involve more than one pairwise comparison or an overall comparison. This is a general statistical issue, not evidence that any particular testing strategy was used. The analysis plan, any hierarchy among comparisons, and any adjustment for multiple testing are not reported in the registry record. The record also does not report whether interim analyses were conducted.

The analysis population is described as 52 patients. Six of the 62 randomized patients did not receive intervention, and another four discontinued without follow-up data. A week 4 MFIS score was used when a participant withdrew before week 8. The registry does not explain whether those participants were included in other analyses, give a complete accounting of missing values by group, or report sensitivity analyses. It also does not report an intention-to-treat analysis or another defined analysis population beyond the stated count included in the analysis.

These omissions limit assessment of selection and missing-data effects. They do not establish that the analysis was biased, but they prevent readers from checking how the available outcomes relate to all randomized participants or how conclusions might change under alternative assumptions.

11. 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 registry’s adverse-event listings report zero serious adverse events in each group. The at-risk counts are 17 for high-dose aspirin, 15 for low-dose aspirin, and 20 for placebo. These are the group-specific counts recorded for the adverse-event listings; they should not be confused with the 52 patients described as included in the primary-outcome analysis.

The listings also report other adverse events affecting 5 in the high-dose group, 0 in the low-dose group, and 3 in the placebo group. These counts describe the registry’s recorded adverse-event categories, not a comparison adjusted for differences in group size or follow-up. The record lists no serious adverse-event terms. Death counts are not reported in the registry record; an unreported value should not be read as a zero.

Adverse-event counts are descriptive. Without further information about event definitions, timing, severity categories, ascertainment, and statistical comparisons, they do not establish whether differences between groups are meaningful or attributable to treatment. Zero recorded serious events in these listings does not prove that no serious events occurred outside the recorded reporting scope.

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

The record establishes that a randomized, double-blind, parallel Phase 3 study compared high-dose aspirin, low-dose aspirin, and matching placebo for multiple sclerosis-related fatigue. It identifies the Modified Fatigue Impact Scale as the primary outcome and explains the scale’s direction: lower scores represent less fatigue-related impact on functioning, while higher scores represent greater impact. It also records the analyzed population and a rule using week 4 scores for participants who withdrew before week 8.

Those details do not establish whether either aspirin regimen changed fatigue-related impact or differed from placebo. Numerical outcome results and analyses are not reported in the registry record. No treatment-effect estimates, uncertainty intervals, or p-values are available to describe the magnitude, precision, or statistical evidence of any comparison. A treatment conclusion would therefore go beyond what the record reports.

The analysis population was smaller than the randomized population, and the stated follow-up gaps make the handling of missing outcome information important. The record does not report enough detail to assess the impact of missingness or whether the analysis represents all randomized participants. Similarly, the terminated status does not explain why the study ended and cannot be taken as evidence for or against a treatment effect.

The adverse-event listings report no serious adverse events in the group records and list other adverse events in the high-dose, low-dose, and placebo groups. Those counts are descriptive and do not by themselves establish comparative safety. Death counts are not reported in the registry record.

Overall, the registry record supports a description of the question, design, outcome measure, participant flow, and recorded adverse-event counts. It does not support a conclusion about treatment efficacy, the size of any effect, or the precision of an effect estimate.

13. Why This Trial Matters Statistically

This study illustrates why a clear outcome definition is not enough to interpret a trial’s result. The registry explains the Modified Fatigue Impact Scale, its score range, and the direction in which scores should be read. Those details matter because a numerical change has meaning only when readers know what the measure captures and whether higher or lower values correspond to greater impact.

It also illustrates the distinction between design information and inferential results. Randomization, masking, and a parallel-group structure describe how a study was organized. They do not show what the treatment groups experienced. Without the numerical outcome values and analyses, readers cannot assess the size or precision of the comparative effect, even when the primary measure is clearly named.

The participant accounting is statistically relevant as well. The registry says that 62 patients were randomized and 52 were included in the analysis, with six not receiving intervention and four more discontinuing without follow-up data. This makes the analysis population and missing-data approach important parts of interpretation. The stated use of a week 4 score for a participant who withdrew before week 8 is a specific rule, but the record does not describe the broader handling of missing values.

Finally, the three-group design raises general questions about which comparisons were planned and how multiple tests were addressed. The registry record does not provide those details. The study is therefore a useful reminder that statistical interpretation depends not only on the endpoint and design, but also on reported results, analysis methods, and transparent accounting of missing data.

14. 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 central limitation for interpreting this study from the registry record is the absence of numerical primary-outcome results. Although the Modified Fatigue Impact Scale and its measurement schedule are described, the record does not report group means, standard deviations, changes, treatment contrasts, confidence intervals, or p-values. The registry lists zero analyses, so the comparative effect and its precision cannot be evaluated.

Participant follow-up is another limitation. Of 62 randomized patients, 6 did not receive intervention and an additional 4 discontinued without follow-up data; 52 were included in the analysis. The record says a week 4 score was used for a participant who withdrew before week 8, but does not report the number of such participants beyond the incomplete wording in the population description. It does not give reasons for discontinuation, group-specific missing-outcome counts, or further missing-data methods.

The registry identifies a three-group design but does not report the planned primary contrast, the statistical analysis plan, or any adjustment for multiple comparisons. It also does not report whether interim analyses occurred. Without these details, the intended inferential framework cannot be reconstructed from the registry record.

The status is listed as terminated, but the reason is not reported in the registry record. The start and primary-completion dates and termination status do not explain the circumstances of termination. The record also does not identify who was masked under the double-blind designation. These omissions limit design appraisal but should not be filled in by assumption.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Aspirin for Treatment of Multiple Sclerosis-Related Fatigue — NCT00467584.
• Registry record last updated 2014-05-20; status last verified 2014-05.
• Results first posted 2014-05-16.
• 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.

18. Record Summary

The registry record describes a randomized, double-blind, parallel Phase 3 study sponsored by Mayo Clinic, comparing high-dose aspirin, low-dose aspirin, and matching placebo for multiple sclerosis-related fatigue. The primary measure was the Modified Fatigue Impact Scale, assessed at baseline and 8 weeks, with a week 4 score used for a participant who withdrew before week 8.

Sixty-two patients were randomized. Six did not receive intervention, and an additional four discontinued without follow-up data; 52 were included in the analysis. The study status is terminated, and its reason is not reported in the registry record.

Numerical primary-outcome results and statistical analyses are not reported in the registry record. The adverse-event listings report zero serious events in each group and list other affected counts of 5, 0, and 3 for high-dose aspirin, low-dose aspirin, and placebo, respectively. Death counts are not reported.