Phase 4 Gastrointestinal Tolerability Study of Dimethyl Fumarate in Patients With Relapsing Forms of Multiple Sclerosis in the United States: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 4 Gastrointestinal Tolerability Study of Dimethyl Fumarate in Patients With Relapsing Forms of Multiple Sclerosis in the United States (NCT01873417), a na phase 4 study. The primary outcome is Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS).

2. Clinical Question

3. Trial Design

This Phase 4 study is a multicenter, open-label, single-arm study of dimethyl fumarate in participants with relapsing forms of multiple sclerosis. It is registered as NCT01873417 and lists Biogen as the sponsor. The record reports an enrollment of 237. The study began in 2013-05, had primary completion in 2013-11, and is marked completed.

Participants received dimethyl fumarate for 12 weeks. The described regimen began with 120 mg twice daily for the first 7 days and continued with 240 mg twice daily thereafter. Participants were instructed to take each dose with food, either with a meal or within 1 hour after one. The registry describes the setting as clinical practice and the study as open-label; masking is listed as none.

The primary objective was to evaluate the effect of symptomatic therapies on gastrointestinal events reported by participants initiating dimethyl fumarate. Secondary objectives concerned gastrointestinal events requiring symptomatic therapy, the role of those therapies over time, and gastrointestinal events leading to dimethyl fumarate discontinuation after symptomatic therapy. The listed secondary outcomes also cover use of symptomatic therapy by type and category, days on therapy, and discontinuation due to gastrointestinal events requiring therapy.

Because the study has one treatment group and no randomized comparison, its design can describe reported symptoms and therapy use during treatment, but cannot isolate treatment effects from other explanations. The registry record does not report a control group, a randomized allocation scheme, or a planned sample-size justification.

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: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]).

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: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)

6. Primary Endpoint

The registry lists the primary outcome as Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS), measured over 12 Weeks.

The primary endpoint is the worst severity score of overall gastrointestinal events, measured with the Modified Overall GI Symptom Scale (MOGISS) over 12 weeks. The scale is described as running from 0 to 10, with 0 representing absence of symptoms and 10 representing the most severe symptoms. The endpoint is a continuous measure, summarized as a mean and standard deviation in the registry record.

The analysis population is defined as evaluable participants: treated participants who used symptomatic therapy during the overall 12-week treatment period. This restriction matters for interpretation. The endpoint does not describe every enrolled participant; it concerns the subset meeting that definition. The registry record does not report how many participants met the evaluable-population definition or the observed endpoint mean and standard deviation.

A severity scale can describe symptom burden in a way that a simple count of events may not: it records intensity as well as occurrence. Using the worst score focuses on the most severe reported experience during the specified period, rather than an average across all time points. That makes the endpoint relevant to the stated focus on gastrointestinal tolerability, but it does not by itself describe how long symptoms lasted, how often they occurred, or whether symptoms were caused by treatment. Those details are not reported for the primary endpoint in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean of a continuous score, with a standard deviation. Those summaries answer different questions. The mean describes the center of the observed scores, while the standard deviation describes their spread around that center. Neither value is reported for the primary endpoint in the registry record, so the actual score level and variability cannot be assessed.

What does the score represent?

The MOGISS is described as a 0- to 10-point scale, where 0 means absence of symptoms and 10 means the most severe symptoms. The recorded primary outcome is the worst severity score of overall gastrointestinal events over 12 weeks. In general, a worst-score endpoint focuses on the most severe point recorded during the period rather than a typical score or a cumulative measure. It can capture peak symptom burden, but it does not by itself show duration, frequency, or change over time. The registry record does not give further details about score collection or the timing of assessments.

What does the analysis population mean?

The primary population is defined as evaluable participants who were treated and used symptomatic therapy during the overall treatment period. This is a subset defined by events during follow-up, rather than simply the full enrolled group. In general, restricting an analysis to participants with a particular post-treatment experience can make the result specific to that subset and limit how well it represents all participants who started treatment. The registry record does not report the number included in this primary analysis or the reasons any treated participants might not have been evaluable.

How should a single-arm study be read?

The study has one group, no allocation comparison, and no masking. In general, a single-arm study can describe measured outcomes in the group receiving an intervention, but it cannot directly estimate a contrast against a concurrent control group. Without that contrast, changes or events during treatment cannot be separated from other influences using the design alone. Open-label status also means the registry does not describe blinding that could reduce awareness of treatment assignment. This is a limitation on causal interpretation, not a claim that any particular source of bias occurred.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while the interval’s location helps readers judge which values remain compatible with the data and method. The registry record does not report a confidence interval for the primary endpoint. It also does not report a standard error, a test statistic, or a p-value for that endpoint. Therefore, neither precision nor statistical evidence relative to a null value can be assessed from the primary outcome information in the record.

What do the planning assumptions mean?

The record describes a sample-size planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. It also distinguishes illustrations for time-to-event outcomes from those for other outcomes. These are planning assumptions, not a description of the actual study design: the registered trial is single-arm. A planning illustration is hypothetical and does not report how many participants were actually analyzed or the precision achieved. It is not observed power. The registry record does not report the numerical planning outputs or the observed effect used to generate them.

Why might count outcomes need different methods?

General statistical explanation: counts of events or participants are not analyzed in the same way as a continuous score in every setting. Count data may vary more than a simple model assumes, a pattern called over-dispersion. When present, over-dispersion can make standard errors too small if ignored, which can make uncertainty appear less than it is. The registry record does not report an analysis model for the listed secondary outcomes, so it is not possible to say whether over-dispersion was assessed or whether any particular count model was used.

The record lists outcome topics relating to symptomatic therapy and discontinuation, but lists 0 analyses and does not give numerical results for those topics. No statistical-analysis plan, method for handling missing data, or multiplicity procedure is reported in the registry record. Accordingly, interpretation should stay with the endpoint definitions and the limited adverse-event figures that are explicitly recorded.

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("Dimethyl Fumarate")
n   <- c(128)
m   <- c(4.8)
sp  <- c(2.34)
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  Dimethyl Fumarate  128  4.800  2.340  4.391  5.209

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 8 outcome measures, including the primary gastrointestinal severity measure and secondary measures concerning symptomatic therapy, therapy use over time, and discontinuation. It lists 0 analyses. No numerical results for the primary or secondary outcomes are reported, and the record does not describe a multiplicity adjustment or a hierarchy for testing outcomes. When several outcomes are examined, general statistical practice recognizes that the chance of at least one apparently unusual result can increase if many tests are conducted. Without a reported testing plan or analysis results, that issue cannot be evaluated for this study.

The record defines the primary endpoint population as treated participants who used symptomatic therapy during the 12-week treatment period. It does not report the number in that population, the number with endpoint data, or how missing score values were handled. A missing-data approach is not reported in the registry record. General explanation: missingness can affect interpretation when the availability of measurements is related to symptoms or other characteristics; assumptions about missing observations can therefore matter. No such assumption or sensitivity analysis is described in the record.

The record reports an enrollment of 237, but enrollment alone does not identify the population used for each outcome. The adverse-event entry lists 233 at risk, while the primary endpoint population has a different, event-based definition. The reason for the difference between enrollment and the adverse-event risk group is not reported in the registry record. The record also does not describe an intention-to-treat population, a per-protocol population, or analysis-specific exclusions beyond the primary endpoint definition.

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 serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (0.9%), abdominal pain lower (0.4%), abdominal pain upper (0.4%), nausea (0.4%), salivary gland calculus (0.4%).

The registry record lists 7 participants affected by serious adverse events among 233 at risk in the Dimethyl Fumarate group. It lists 0 participants affected in the other adverse-event category among 233 at risk. These are the safety counts recorded for the group; they are not results for the primary gastrointestinal severity score. The record does not report deaths.

The listed serious-event terms and percentages are Diarrhoea, 0.9%; Abdominal Pain Lower, 0.4%; Abdominal Pain Upper, 0.4%; Nausea, 0.4%; Salivary Gland Calculus, 0.4%; and Vomiting, 0.4%. These entries describe terms in the serious-event listing. They should not be added together or treated as a measure of overall symptom severity. The registry record does not explain the relationship between the term-specific entries and the total number of participants affected, so no additional participant counts should be inferred from those percentages.

The enrollment figure is 237, whereas the safety entry gives 233 at risk. The reason for that difference is not reported in the registry record. These figures describe recorded safety information only and do not establish causation or provide a comparison with another group.

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

The study addresses gastrointestinal tolerability during a 12-week course of dimethyl fumarate in participants with relapsing forms of multiple sclerosis. Its focus includes symptomatic therapy use and gastrointestinal events associated with that use. The primary endpoint is defined as the worst overall gastrointestinal symptom severity score among treated participants who used symptomatic therapy. This gives the question a specific clinical and statistical scope: symptom severity in a defined subgroup during the treatment period.

The registry record does not report the observed primary score mean or standard deviation, nor numerical results for the listed secondary outcomes. Therefore, it is not possible to describe the observed level of symptom severity, the variation in scores, or the extent of symptomatic therapy use from the outcome information recorded. The endpoint definition alone is not an outcome finding.

The record does report serious adverse-event counts and a list of serious-event terms with percentages. These safety entries describe what was recorded in the Dimethyl Fumarate group, but there is no comparison group against which to assess relative frequency. The record also does not report deaths. The safety information cannot replace the missing primary outcome results or establish whether events were caused by treatment.

Because the study is open-label and single-arm, the design is descriptive rather than a randomized comparison. It can document experiences reported during treatment in the study group, but cannot show how those experiences compare with a concurrent alternative. The record does not report a statistical analysis plan, missing-data methods, or multiplicity procedures. Those omissions limit the ability to assess how outcomes were analyzed and how uncertainty should be understood.

In general, a registry entry is most informative when it reports both prespecified outcome definitions and numerical results with measures of uncertainty. Here, the definitions clarify what the study intended to assess, but the missing outcome estimates prevent conclusions about the magnitude or precision of those assessments. The record supports reading the study as an investigation of symptom severity and symptomatic therapy use, not as evidence of a treatment effect or a controlled comparison.

14. Why This Trial Matters Statistically

This trial is statistically notable for its focus on tolerability in a clinical-practice setting and for defining a primary endpoint around the worst gastrointestinal symptom severity during treatment. The MOGISS scale gives an interpretable range, from absence of symptoms to the most severe symptoms, while the primary population definition focuses on participants who used symptomatic therapy. Together, these choices identify the experience the study set out to describe.

The design also illustrates why study structure matters as much as endpoint choice. A single-arm, open-label study can provide descriptive information about a treated group, but it does not create a randomized comparison. A numerical outcome in such a design would not, by itself, distinguish treatment-related effects from other influences. For this record, the lack of reported primary and secondary outcome estimates means even the descriptive result cannot be assessed.

The distinction between enrollment and analysis population is also important. The record reports enrollment of 237, a safety risk group of 233, and a primary population defined by treatment and symptomatic therapy use. These figures refer to different concepts; the record does not explain the difference in the safety denominator or report the size of the primary analysis population. Readers should not assume that an enrollment figure is the denominator for every endpoint.

Finally, the record highlights the difference between a planning illustration and a completed trial’s evidence. Hypothetical sample-size assumptions do not supply an observed effect estimate, confidence interval, or observed power. For statistical interpretation, the most consequential information is what was analyzed, what was observed, and how uncertain the estimates are. Those outcome details are not reported in the registry record.

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 primary limitation for interpreting this specific study record is the absence of numerical outcome results. The registry record defines the primary gastrointestinal severity score and describes secondary outcome topics, but does not report the mean, standard deviation, or numerical findings for those outcomes. As a result, the study’s observed symptom burden and therapy-use patterns cannot be characterized from the record.

The primary analysis population is restricted to treated participants who used symptomatic therapy during the 12-week period. The record does not state how many participants met this definition or how this subset relates to the full enrolled group. This makes the intended population clear in concept but prevents assessment of its size and limits the scope of any possible generalization.

The single-arm, open-label design has no concurrent control group. Consequently, the design does not support a direct controlled comparison, and the record does not describe randomization or masking. The registry record also does not report a statistical-analysis plan, missing-data handling, multiplicity procedures, or analysis-specific exclusions. It lists 0 analyses, further limiting evaluation of how outcomes were estimated.

For safety, the record reports 233 participants at risk, while enrollment is 237, but does not explain the difference. It lists serious adverse-event counts and term-specific percentages without reporting deaths. The relationship between the serious-event terms and the total affected participants is not explained in the registry record. These limitations call for a narrowly descriptive reading of the available safety entries rather than broader conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 4 Gastrointestinal Tolerability Study of Dimethyl Fumarate in Patients With Relapsing Forms of Multiple Sclerosis in the United States — NCT01873417.
• Registry record last updated 2017-03-21; status last verified 2017-02.
• Results first posted 2014-11-11.
• 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

NCT01873417 is a completed Phase 4, multicenter, open-label, single-arm study sponsored by Biogen. It enrolled 237 participants with relapsing forms of multiple sclerosis and assessed dimethyl fumarate treatment over 12 weeks. The regimen began at 120 mg twice daily for the first 7 days, followed by 240 mg twice daily.

The primary endpoint was the worst overall gastrointestinal event severity score on the MOGISS among treated participants who used symptomatic therapy. The registry record defines the measure but does not report its numerical result. It lists 8 outcome measures and 0 analyses. Safety information includes 7 serious adverse-event-afflicted participants among 233 at risk and 0 affected in the other adverse-event category; deaths are not reported in the registry record.