ACTH for Fatigue in Multiple Sclerosis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ACTH for Fatigue in Multiple Sclerosis Patients (NCT02315872), a randomized phase 3 study. The primary outcome is Fatigue at 28 Weeks.

2. Clinical Question

The clinical question concerns fatigue in people with relapsing multiple sclerosis, rather than a broad assessment of every symptom or consequence of the condition. The primary outcome description names two instruments: the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS). Both are patient-reported measures, so the endpoint reflects participants’ reported experience and the scales’ specified scoring, rather than an objective laboratory measurement.

The registry identifies ACTH and placebo as the interventions in a randomized, parallel-group trial. It does not report numerical primary-outcome scores for either group, a between-group estimate, or an inferential analysis. Therefore the posted record does not answer, quantitatively, how the fatigue scores compared at the stated time point. Depression, sleepiness, and quality of life are listed as secondary outcomes, but their results are not reported in the registry record.

3. Trial Design

The registry describes a phase 3, randomized, triple-masked, parallel-group trial comparing ACTH with placebo. Enrollment is listed as 8. The record identifies Providence Health & Services as the sponsor and lists the study status as completed. The study start date is 2015-05-22, and the primary completion date is 2017-06-20.

In a parallel-group design, participants are assigned to one intervention group and remain in that group for the comparison. Random assignment is intended to reduce systematic differences between groups at the point of allocation. Masking is intended to limit the influence of treatment knowledge on participant reports, care, or outcome assessment. The registry labels the study triple-masked but does not identify which roles were masked or describe how masking was implemented.

The ACTH description states that the drug was to be given subcutaneously twice weekly for 2 weeks, with an increase from 40 units to 80 units twice weekly if the initial regimen was tolerated. It also mentions a dose reduction if the higher dose was not tolerated, but the description ends before the subsequent regimen is fully specified. The placebo description states twice-weekly subcutaneous administration for 28 weeks. The registry record does not report adherence, treatment discontinuation, or actual exposure by group.

The target outcome time point is 28 weeks. The record lists depression, sleepiness, and quality of life at 28 weeks as secondary outcomes. It does not report the trial’s sample-size justification, allocation concealment procedures, or a detailed statistical analysis plan. The completed status and the primary completion date describe the record’s study status and timing; they do not by themselves establish that results were analyzed or reported.

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 Fatigue at 28 Weeks, measured over 28 weeks.

The primary endpoint is described as fatigue at 28 weeks, measured using patient-reported scores on the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS). The MFIS has 21 items and assesses the impact of fatigue on a person’s activities. The FSS has 9 items and measures fatigue severity and its effect on activities and lifestyle among people with a variety of disorders. On both scales, higher scores indicate greater fatigue impact or severity.

These instruments address related but not identical aspects of fatigue. One focuses on the impact of fatigue on activities, while the other covers severity and effects on activities and lifestyle. Patient reports are relevant when the outcome of interest is the participant’s experienced fatigue, but scores remain dependent on the instruments’ wording, scoring, and the participant’s responses. The registry describes the primary outcome using a median and full range, but it reports no score values for either group.

A stated time point makes the intended assessment window clear, while the use of two scales means the primary outcome description is not a single numerical measure. The record does not specify how the two scales were to be combined, prioritized, or interpreted together. It also does not report numerical results, missing-score counts, or a comparison between groups. Thus, the endpoint definition explains what was intended to be measured, but the registry record does not provide the observations needed to assess the treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to intervention groups by chance. In general, its purpose is to reduce systematic differences between groups, so that a well-conducted comparison can be interpreted as an estimate of the effect of assignment to the interventions under study. Randomization does not guarantee that groups will be identical, particularly in a small trial. The registry labels this trial randomized but does not report the allocation sequence or concealment procedures.

A parallel-group design compares separate groups over the study period. The ACTH and placebo groups are the two listed arms. In this design, the main comparison ordinarily concerns outcomes between the assigned groups at a specified time point, subject to the analysis plan and available observations. The registry identifies 28 weeks as the primary outcome time point, but it does not provide a numerical group comparison or describe an analysis population.

Masking means that some people involved in a study are not told which intervention a participant received. It can reduce the risk that expectations influence reports or assessments. The registry uses the label triple-masked, but does not say which three roles were masked, whether masking was maintained, or how treatment assignment was concealed. Those details are not reported in the registry record, so the label alone does not resolve how masking operated in practice.

The endpoint uses two patient-reported scales. In general, a score is a constructed measure based on responses to multiple questions. The MFIS assesses fatigue’s impact on activities; the FSS assesses fatigue severity and effects on activities and lifestyle. Higher scores on each are described as indicating greater fatigue. Because these scales are distinct, a statistical analysis needs to make clear whether each is treated as a separate primary measure, whether one is prioritized, or whether some combined approach is used. That hierarchy or combination is not reported in the registry record.

The registry describes the primary outcome summary as a median with a full range. In general, the median is the middle value after observations are ordered, while the full range gives the minimum and maximum. These summaries can be useful when score distributions are skewed or when a small set of observations makes the tails important to display. They do not, on their own, quantify the uncertainty in a between-group effect. An inferential comparison might report an effect estimate and an uncertainty interval, but neither is present for this primary outcome.

For continuous outcomes, the analysis method should match the estimand, score properties, and study design. A mean difference, a difference in medians, or a model-based contrast answers a specific statistical question; these are not interchangeable descriptions. The registry record does not state which contrast was planned, whether any adjustment was intended, or which test or model was used. No method should be attributed to the investigators without that information.

Over-dispersion is a general issue for count outcomes: it occurs when variation in the data exceeds what a simple model assumes, and can make standard errors too small if ignored. It is not directly a description of these fatigue scores, and the registry does not report a count model or an over-dispersion assessment. More generally, model assumptions should be judged in relation to the outcome and data actually analyzed; those data and diagnostics are not reported in the registry record.

The record lists zero analyses, and it does not give a primary-outcome estimate, confidence interval, or p-value. The stated sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such planning calculations are hypothetical illustrations, not observed power and not evidence about the trial’s outcome. The record does not report the specific planning estimates or the trial’s own sample-size justification. Because the primary outcome has several categories or time points and was not reduced to one comparison, no single primary effect is available to interpret as a basis for a planning illustration.

Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, testing many hypotheses can increase the chance of finding an apparently notable result by chance unless the analysis strategy accounts for that multiplicity. The two fatigue scales and listed secondary outcomes make a prespecified hierarchy or adjustment approach relevant to interpretation. Such an approach is not reported in the registry record. A reader therefore cannot determine which result was designated as decisive or whether any multiplicity control was planned.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description names two fatigue measures, MFIS and FSS, and the registry indicates that the primary outcome has several categories or time points rather than one reduced comparison. The record also lists depression, sleepiness, and quality of life at 28 weeks as secondary outcomes. When a study considers multiple outcomes or comparisons, multiplicity is a general concern: the chance of at least one apparently unusual finding can increase as more hypotheses are examined. The registry record does not report a prespecified hierarchy among the fatigue measures, a multiplicity adjustment, or another strategy for interpreting multiple tests.

Missing data can affect both the summary of outcomes and the comparison between groups. For example, participants with unavailable scores may differ from those with observed scores. General approaches include analyzing available observations under stated assumptions, using imputation, or applying a model that accommodates incomplete data. The appropriate approach depends on why values are missing and on the analysis plan. The registry record does not report missing primary-outcome counts, reasons for missingness, or a method for handling missing scores.

An analysis population defines which randomized participants contribute to a particular analysis. Common approaches can include analyzing participants according to assigned group or restricting an analysis to those meeting specified criteria, but the choice and its justification should be documented. The registry record does not identify the population used for primary or secondary analyses. Although it lists 8 enrolled participants, that does not establish how many contributed outcome data or how they were included in any analysis. These omissions limit assessment of the analysis and its potential for bias.

11. 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 adverse-event record lists the ACTH and placebo groups separately. For serious adverse events, it reports 0 affected among 4 at risk in each group. It reports 0 deaths in each group. For other adverse events, it reports 4 affected among 4 at risk in the ACTH group and 3 affected among 4 at risk in the placebo group. These are the counts recorded; the registry does not provide event descriptions for the other adverse events in this summary.

Serious and other adverse events are different categories in the record and should not be conflated. The reported absence of serious events does not mean that no adverse events of any kind occurred, as the other-event counts show. Conversely, these counts alone do not establish that an event was caused by an intervention. The record does not provide enough detail to assess event type, timing, severity within the non-serious category, or attribution.

The groups are small, so the counts should be read as descriptive observations rather than as a precise comparison of safety. The registry does not report a statistical comparison of adverse events, nor does it provide further detail on how events were collected. The figures describe what was entered in this record; they are not a complete basis for characterizing comparative safety.

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

The record supports a limited set of conclusions about trial conduct and reporting. It identifies a completed, randomized, triple-masked, parallel-group phase 3 trial of ACTH versus placebo in people with relapsing multiple sclerosis experiencing chronic fatigue. It specifies fatigue measures and a 28-week assessment time point, and it lists several secondary outcomes. These registry entries describe the question the trial set out to address.

The record does not provide numerical results for the primary fatigue outcome, a treatment contrast, a confidence interval, or a p-value. It therefore cannot establish the direction or size of any difference between groups, or how precisely such a difference was estimated. The absence of a posted estimate is not proof of no effect, and it is not evidence that the interventions were equivalent. Equivalence or non-inferiority would require a defined margin and an analysis designed to address that question; these are not reported in the registry record.

Likewise, the safety counts are descriptive. The record reports no serious adverse events or deaths in either listed group, and it reports other adverse events in both groups. Those observations do not by themselves establish comparative safety, causation, or the likelihood of future events. Details about the types and timing of the other adverse events are not reported in the registry record.

Enrollment is listed as 8, but outcome-data availability and the analysis population are not reported. A reader cannot infer from enrollment alone how many participants contributed to each outcome analysis. The record also does not report how missing scores, multiple measures, or multiple comparisons were handled. These limitations matter because they affect both the validity and the precision of statistical conclusions.

Accordingly, the registry entry is informative about the trial’s design and intended measurements but does not provide the results needed to judge the primary comparison. It should not be treated as evidence that ACTH did or did not change fatigue scores. Any interpretation beyond the stated design, outcome definitions, and recorded event counts would require information that is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues in a compact setting. The planned comparison uses randomization and masking, features intended to reduce bias in treatment assignment and outcome assessment. At the same time, enrollment is listed as 8, making the amount of information available for estimating group differences a central consideration. In general, limited information can lead to substantial uncertainty and sensitivity to individual observations. The registry record does not provide an effect estimate or uncertainty interval with which to assess that uncertainty directly.

The outcome definition also matters. Fatigue is assessed by two patient-reported instruments with related but distinct emphases. A clear analysis plan would explain how those measures contribute to the primary question and how multiple outcomes or time points are interpreted. The record does not report that hierarchy or the handling of multiplicity. This is important because a reader needs to know which comparison the trial was designed to answer, rather than selecting one result after examining many possibilities.

The record further illustrates the difference between a completed study and a statistically interpretable result. It supplies design details, intervention descriptions, and adverse-event counts, but no primary-outcome analysis. Without numerical results and methods, the central fatigue comparison cannot be evaluated for magnitude or precision. These reporting gaps are not evidence about the treatment effect; they define what can and cannot be concluded from this entry.

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 most direct limitation is that the registry record does not report numerical results for the primary fatigue measures. It does not give group medians or ranges, an effect estimate, an uncertainty interval, or a p-value. The record lists zero analyses, so there is no reported inferential result to interpret. The intended summary is identified as a median with a full range, but the corresponding values are absent.

The primary outcome is described using both MFIS and FSS, and it is flagged as involving several categories or time points rather than one comparison. The registry does not explain how the measures were prioritized or whether they were analyzed separately. Nor does it report how multiplicity was handled. This leaves the exact primary statistical question unclear beyond the named measures and 28-week time point.

Enrollment is listed as 8, but the record does not state how many participants completed each assessment, how many had missing scores, or which analysis population was used. It does not describe adherence, withdrawals, or reasons for missing data. The ACTH dosing description is truncated, so the full planned regimen cannot be reconstructed from the registry entry. Masking is labeled triple, but the masked roles and procedures are not specified.

The adverse-event summary gives group counts but not event names, timing, severity details for other events, or attribution. The record also does not report the trial’s sample-size justification or detailed statistical plan. These limitations constrain assessment of both efficacy and safety; they do not establish a positive, negative, or null treatment effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ACTH for Fatigue in Multiple Sclerosis Patients — NCT02315872.
• Registry record last updated 2019-09-09; status last verified 2019-08.
• Results first posted 2019-08-13.
• 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 describes NCT02315872, titled “ACTH for Fatigue in Multiple Sclerosis Patients,” as a completed phase 3 randomized, triple-masked, parallel-group trial sponsored by Providence Health & Services. It lists enrollment as 8 and the condition as relapsing-remitting multiple sclerosis. The study start date is 2015-05-22, and the primary completion date is 2017-06-20.

The trial compares ACTH with placebo. Its primary outcome is fatigue at 28 weeks, measured with the MFIS and FSS; depression, sleepiness, and quality of life are listed as secondary outcomes. The registry record does not report numerical primary-outcome results or analyses. Its adverse-event summary reports no serious adverse events or deaths in either group, while other adverse events are recorded in both groups. Missing-data methods, analysis populations, multiplicity handling, and the complete ACTH dosing description are not reported in the registry record.