This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of ACTHAR on Advanced MRI Surrogate Markers of Disease Activity and on Comprehensive Immune Signature During MS Relapses (NCT03021317), a na phase 4 study. The primary outcome is Change in T1 Lesion Relaxation Time.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03021317 |
| Phase | Phase 4 |
| Condition | Multiple Sclerosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Chicago |
| Results posted | Yes |
2. Clinical Question
Population
People with multiple sclerosis who were undergoing an acute relapse. The registry record states that no participants started the trial and received the intervention, so it does not provide observations from a treated population.
Intervention
ACTHAR, administered in an open-label treatment study. The study description says treatment was planned for 10 days, with initiation within 48 hours of relapse assessment.
Comparator
No concurrent comparator is described. The study is listed as single group, with no masking and no randomized allocation. The proposed assessment follows participants across time rather than comparing treatment groups.
Primary question
How would T1 lesion relaxation time, an MRI marker of injury, change over the 12 month period after completion of the intervention? Because no participants started treatment, the registry record reports no observed change.
The study was designed to examine MRI and laboratory markers during and after an acute multiple sclerosis relapse. Its primary endpoint was change in T1 lesion relaxation time. The registry description says this measure would be followed over time to assess whether lesions recover after ACTHAR intervention. Serial MRI was planned at baseline, 1 month after the first dose, and months 3, 6, and 12. The study also planned serial immune assays using serum and blood samples at baseline, the last day of ACTHAR, 1 month after the first dose, and months 3 and 6.
This is a within-group, longitudinal question, not a randomized treatment comparison. The record does not set out a control group or a treatment-versus-control effect. The planned measurements could describe how MRI and laboratory markers change over time in participants who received treatment, but the registry record reports that no participants started the trial and received the intervention. It therefore cannot answer the planned question using observed participant outcomes. The record does not report a treatment effect, an estimate of change in the primary endpoint, or a comparison with another treatment or with no intervention.
3. Trial Design
The registry record identifies this as a phase 4 study sponsored by the University of Chicago. Its title concerns ACTHAR, MRI surrogate markers of disease activity, and immune signatures during multiple sclerosis relapses. The design is listed as single group, with no masking and no randomized allocation. The treated group is described as an open-label, single-arm treatment study using MRI and laboratory markers. Thus, the planned data structure was repeated assessment over time in treated participants, rather than a comparison between independently assigned groups.
The record lists enrollment as 5 and gives the study status as terminated. It also states that no participants started the trial and received the intervention. The enrollment field should not be mistaken for evidence that 5 people received ACTHAR or contributed endpoint data: the record explicitly reports no treated participants for the primary outcome. The start date is 2016-12-20, and the primary completion date is 2020-10-07.
The brief description says ACTHAR was planned for 10 days, beginning within 48 hours of relapse assessment. MRI assessments were planned at baseline, 1 month after the first dose, and months 3, 6, and 12. Blood and serum collection for immune assays was planned at baseline, on the last day of treatment, 1 month after the first dose, and months 3 and 6. These are planned procedures, not evidence that assessments took place.
The registry record does not report the reason for termination, the actual recruitment history, protocol deviations, or whether any measurements were collected before termination. It does not report a comparator arm, masking procedures beyond listing masking as none, or a detailed analysis plan. No outcome analyses are 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.
Before assignment: No participants started the trial and received the intervention.
Overall Study
| Stage | Treated Group |
|---|---|
| STARTED | 0 |
| COMPLETED | 0 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: No participants started the trial and received the intervention.
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: No participants started the trial and received the intervention.
| Characteristic | Unit | Treated Group |
|---|---|---|
| Participants analysed | 0 | |
| Age, Categorical: <=18 years | — | |
| Age, Categorical: Between 18 and 65 years | — | |
| Age, Categorical: >=65 years | — | |
| Sex: Female, Male: Female | — | |
| Sex: Female, Male: Male | — | |
| Region of Enrollment: United States | — |
6. Primary Endpoint
The registry lists the primary outcome as Change in T1 Lesion Relaxation Time, measured over 12 month after the completion of intervention.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in T1 lesion relaxation time. The registry describes T1 relaxation time as an MRI marker of injury and specifies that change would be followed over 12 month after completion of the intervention. The endpoint is intended to track a lesion-related MRI characteristic over time, rather than to report a direct comparison of treatment groups.
In general, a repeated imaging measure can describe whether a marker changes between assessments. A change in an imaging marker is not automatically equivalent to a change in symptoms, disability, or another clinical outcome. The interpretation depends on what the marker represents, how it is measured, and whether the observed change can be distinguished from measurement variability and other influences. Those general considerations do not establish that any particular change occurred in this study.
The registry record gives no unit, numerical endpoint value, estimate of change, measure of variability, or confidence interval. It states that no participants started the trial and received the intervention. Consequently, there is no reported primary endpoint observation to interpret, and the proposed marker cannot be assessed from participant data in this record. The stated timeframe and rationale describe the planned endpoint, not a result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry record reports no participants started the trial and received the intervention. Accordingly, it provides no observed primary endpoint value, no estimate of change in T1 lesion relaxation time, and no measure of precision for that change. The record does not report an outcome analysis. It is therefore not possible to characterize an effect estimate as favorable, unfavorable, large, small, or uncertain: there is no reported estimate to characterize.
The record lists enrollment as 5, but that entry does not override the outcome population statement. The primary outcome description explicitly says that no participants started the trial and received the intervention. Enrollment and exposure to the intervention are distinct concepts; the listing of a planned or recorded enrollment figure alone does not establish that participants received treatment, completed imaging, or contributed endpoint data. The registry record does not explain the relationship between the enrollment entry and the statement about no treated participants.
The single-group, open-label design would have called for interpreting repeated measurements over time without a concurrent randomized control group. General statistical interpretation of a before-and-after pattern would need to account for natural changes over time, measurement variability, and other influences that could coincide with treatment. Without a comparator, a change within the treated group would not by itself isolate the contribution of ACTHAR. In this record, however, even such a within-group change is unavailable because no participants started treatment.
No confidence interval or p-value is reported for the primary endpoint, and no primary outcome analysis is listed. This means there is no basis for describing statistical significance or precision. It also means that absence of a reported result should not be interpreted as evidence that the marker did not change. The record is silent on an observed change because it reports no treated participants, rather than documenting a measured result close to no change.
The registry lists a secondary outcome concerning change in immune subset expression in CD4+FOXP3 Tregs by flow cytometry after ACTHAR intervention. The record supplies no numerical result or analysis for this outcome. The same distinction applies: the endpoint's inclusion describes a planned measurement, not evidence that it was collected or changed.
The adverse-event entry shows zero participants at risk and zero events in the treated group, consistent with the record's statement that no participants received the intervention. Those entries cannot establish that ACTHAR caused no adverse events among treated participants, because the record does not describe an exposed participant group. The record also does not report a reason for termination, so termination itself should not be attributed to any particular safety, efficacy, recruitment, or operational cause.
9. Statistical Methods Explained
What does a single-group repeated-measures design estimate?
General explanation: In a single-group longitudinal study, the same participants are intended to be measured at more than one time. The analysis can describe the observed values at each assessment and the pattern of change within participants. This is different from estimating a randomized treatment contrast, which compares outcomes between groups assigned to different conditions. A within-group pattern can be affected by factors that change over time as well as by the intervention.
For this study, the planned sequence included baseline and follow-up MRI assessments, with immune assays at specified visits as well. The record does not report participant-level data, summary results, or a statistical analysis for those measurements. As no participants started the trial and received the intervention, there are no reported repeated observations from treated participants on which to estimate a trajectory.
Why does the lack of a comparator matter?
General explanation: A concurrent control group can help distinguish a treatment-associated difference from changes that might have occurred over the same period for other reasons. In a single-group study, a change from baseline is descriptive of the observed course, but it does not independently show what would have happened without the intervention. Open-label status also means that masking is not part of the listed design. The record does not describe any blinded outcome assessment.
The registry classifies this study as single group, with no randomized allocation and no masking. There is no like-for-like control comparison. These design features matter when interpreting any possible future or historical account of change, but they do not create a result where none is reported.
What would a confidence interval communicate?
General explanation: A confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision under those assumptions, while a wider interval indicates less precision. It does not correct for design limitations, measurement problems, or bias. A confidence interval must be based on an estimate and data; it cannot be interpreted when the estimate is not reported.
The registry record gives no estimate or confidence interval for change in T1 lesion relaxation time. It also reports no primary outcome analysis. Precision therefore cannot be assessed. The absence of a reported interval does not mean that an interval was narrow, wide, or centered at any particular value.
What do the planning assumptions mean?
General explanation: A sample-size calculation is a planning tool for a future study. It depends on assumptions about the effect to detect, variability, allocation, significance level, and analysis method. It is not an observed outcome, and a planning calculation is not a substitute for an effect estimate or confidence interval. Power refers to a design's chance of detecting a specified effect under its assumptions; it is not a measure of whether a completed study demonstrated an effect.
The registry record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. The illustration is not the study's own design: the trial is listed as single group. The record does not report a numerical observed effect for the primary endpoint, because no participants started the trial and received the intervention. Any sample-size illustration therefore should be read as planning material, not as a result or observed power. It does not establish that the study was adequately sized, or that a particular effect was detected.
The registry further distinguishes illustrations for time-to-event outcomes, expressed as a total number of events, from other illustrations expressed as participants per arm. The primary outcome in this study is a change in an MRI measure, not a time-to-event endpoint. The available record does not provide a reported effect estimate or endpoint variance that could support an independent assessment of such planning assumptions.
Why can over-dispersion matter?
General explanation: Over-dispersion occurs when observed variation is greater than a statistical model assumes. If a model underestimates variation, its uncertainty estimates can be too small and inferential conclusions can appear more precise than warranted. The choice of a model and its variance assumptions should fit the outcome and study design. The registry record does not report an analysis model, distributional assumptions for the primary endpoint, or a variance estimate. There is no basis for determining whether over-dispersion was assessed or relevant to the planned primary analysis.
What does a missing analysis plan leave unclear?
The record does not report how the primary endpoint would be calculated from repeated MRI measurements, how incomplete follow-up would be handled, or which statistical model would be used. It does not specify a primary contrast, covariate adjustment, or decision rule for interpreting the endpoint. These details are important for reproducing an analysis and understanding its assumptions. They should not be inferred from the visit schedule or from the study's title. With no participants reported to have started treatment and no outcome analyses reported, the record supports description of the intended design, but not reconstruction of an outcome analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary endpoint of change in T1 lesion relaxation time and a secondary outcome concerning change in immune subset expression in CD4+FOXP3 Tregs by flow cytometry after ACTHAR intervention. It does not report a multiplicity strategy, such as how interpretation would account for testing more than one outcome or multiple time points. It also does not report a hierarchy of secondary analyses or a prespecified adjustment procedure. These details are not reported in the registry record and should not be assumed.
Multiplicity is a general statistical concern when several outcomes, visits, or comparisons are examined. The more analyses considered, the greater the chance that an apparently notable result could arise by chance if each is treated as a separate confirmatory test. A prespecified plan can clarify which analyses are primary and how additional findings should be interpreted. That concept does not imply that any finding was observed in this trial.
The record does not report a missing-data method, rules for incomplete visits, an analysis population definition, or whether an intention-to-treat or per-protocol approach was planned. It states that no participants started the trial and received the intervention. The record does not clarify whether any enrolled individuals had baseline assessments, whether any data were collected before treatment, or whether partial records exist. It therefore does not permit assessment of missingness patterns or the assumptions that an analysis might make about missing data.
The adverse-event record lists no participants at risk in the treated group, and no adverse events. In the context of no treated participants, these entries do not provide evidence about event rates among exposed participants. The record does not report an analysis population for safety or any further safety analysis. These absences limit interpretation; they do not establish a particular missing-data, multiplicity, or safety-analysis procedure.
11. What the Result Does, and Does Not, Mean
The record establishes that a phase 4, open-label, single-group study was registered to examine MRI and immune markers around ACTHAR treatment during multiple sclerosis relapses. It identifies T1 lesion relaxation time as the primary endpoint and describes planned serial imaging and laboratory assessments. It also records that the study was terminated and that no participants started the trial and received the intervention.
Those details mean that no primary endpoint result is available in the registry record. There is no reported estimate of change, no interval describing its precision, and no analysis from which to judge the direction or size of a change. The record cannot show whether the planned MRI marker changed after intervention, nor can it provide a participant-level description of immune-marker changes. Planned measurements and a stated biological rationale are not outcome data.
The design also would not have provided a randomized treatment comparison. In general, a single-group change over time cannot by itself separate treatment effects from other time-related influences. Here, that design limitation is secondary to the more fundamental fact that no treated participants are reported. There is no observed within-group course to interpret, much less a treatment-versus-control effect.
The record does not show that the primary endpoint remained unchanged, that ACTHAR produced a particular result, or that treatment was safe or unsafe in this study. Zero adverse events alongside zero participants at risk cannot be interpreted as evidence about adverse events among treated people. Nor does the terminated status disclose why the study stopped; a reason is not reported in the registry record.
In short, the posted information describes an intended research question and design, but not an outcome finding. Any interpretation should distinguish what the study planned to measure from what the record says was actually observed. It supports no conclusion about the magnitude, precision, or clinical meaning of a treatment-associated change.
12. Why This Trial Matters Statistically
This study is statistically informative as an example of why registered design details and outcome data must be read separately. The title and planned procedures describe a longitudinal investigation of MRI and immune markers, while the primary outcome population states that no participants started the trial and received the intervention. Those statements lead to an important boundary: the registry can describe the intended measurement strategy, but it cannot supply an empirical estimate of change.
The single-group design also illustrates the distinction between tracking change and estimating a treatment contrast. Repeated imaging can be useful for describing a marker's course, but a trajectory in treated participants would not, by itself, establish what would have happened without treatment. That is a general design consideration, not a result from this study. Since no treated participants are reported, even the planned within-group description is unavailable.
The record also makes clear why sample-size planning material must be interpreted in context. The planning assumptions describe a hypothetical calculation, whereas the registered study is single group and no observed primary endpoint effect is reported. Planning illustrations cannot be treated as evidence that an effect was observed or that a study had observed power.
Finally, the record shows the limits of interpreting empty outcome and safety entries. No outcome analysis and no exposed treated group mean that the absence of reported events or results is not an estimate of no effect or no risk. For statistical readers, the key lesson is to distinguish a study's planned question, its registered design, and the data actually available for analysis. In this case, the available record supports the first two descriptions but not a treatment outcome conclusion.
13. 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 main limitation for interpreting this trial record is the absence of participants reported to have started the intervention. The record therefore contains no reported primary endpoint observations and no outcome analysis. It does not say whether MRI or immune measurements were collected from anyone before treatment, or whether any partial data exist. That history is not reported in the registry record.
The study was planned as an open-label, single-group investigation without a randomized comparator. Even if repeated measurements had been reported, changes over time would not have provided a direct randomized comparison with an untreated or alternative-treatment group. The record does not describe blinded assessment or a method to address influences that might change alongside the marker.
The registry does not report a reason for termination. It also does not report a detailed statistical analysis plan, a method for summarizing repeated T1 relaxation time, handling of missing visits, a definition of the analysis population, or an approach to multiple outcomes and time points. No endpoint unit, numerical estimate, variability measure, confidence interval, or p-value is reported. These omissions prevent assessment of outcome magnitude and precision and limit reproducibility.
The record lists enrollment as 5 while stating that no participants started the trial and received the intervention. It does not explain that difference in status or clarify whether the enrollment figure represents actual recruitment or another registry entry. The adverse-event listing reports zero at risk and zero events, but it does not provide an exposed population from which safety could be assessed. These record-specific limitations should not be resolved by inference.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Effects of ACTHAR on Advanced MRI Surrogate Markers of Disease Activity and on Comprehensive Immune Signature During MS Relapses — NCT03021317.
- Registry record last updated 2024-05-16; status last verified 2024-05.
- Results first posted 2024-05-16.
- 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.
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17. Record Summary
The University of Chicago sponsored this phase 4 study of ACTHAR and MRI and immune markers during multiple sclerosis relapses. It is listed as terminated, with a single-group, open-label design and no randomized allocation. The record lists enrollment as 5 but states that no participants started the trial and received the intervention.
The primary endpoint was change in T1 lesion relaxation time over 12 month after completion of the intervention. A secondary outcome concerned change in CD4+FOXP3 Treg immune subset expression by flow cytometry. The study description planned 10 days of ACTHAR and serial MRI and laboratory assessments. No primary or secondary outcome analysis is reported. The record provides no treatment-effect estimate, precision measure, or explanation for termination.