Meningeal Inflammation on 7T MRI as a Tool for Measuring and Predicting Ocrelizumab Response in Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Meningeal Inflammation on 7T MRI as a Tool for Measuring and Predicting Ocrelizumab Response in Multiple Sclerosis (NCT03396822), a registered phase not stated study. The primary outcome is Change in the Number of Enhancing Leptomeningeal Foci on 1 Year Follow up Compared to Baseline in MS Patients Treated With Ocrelizumab..

2. Clinical Question

3. Trial Design

The registry record describes a completed study sponsored by the University of Maryland, Baltimore. It lists enrollment of 24, a start date of 2018-09-24, and a primary completion date of 2023-05-25. The condition is multiple sclerosis. The study title concerns use of 7T MRI to measure and predict response to ocrelizumab, while the primary endpoint is the change in the number of enhancing leptomeningeal foci at one-year follow-up compared with baseline.

The record does not establish a randomized treatment comparison. It explicitly notes that allocation was not stated and that the arms are not a like-for-like control comparison. Therefore, any contrast between arms should not be interpreted as if it arose from random assignment to comparable groups. How participants entered any arms, what those arms represent, and whether their treatment exposures differed are not reported in the registry record.

There is an important ambiguity in the intervention description. The intervention listing names Gadoteridol, whereas the title and primary endpoint describe ocrelizumab-treated participants. The brief summary gives a biological rationale for studying ocrelizumab and meningeal inflammation, but the registry record does not clarify how Gadoteridol relates to the study procedures or treatment. The timing, dose, duration, and administration details for the named intervention are not reported in the registry record.

The record lists three outcome measures, including the primary endpoint and a secondary outcome concerning the proportion of participants with meningeal enhancement after treatment compared with pretreatment baseline. It does not report the numerical results for these outcomes. Details such as masking, recruitment methods, study sites, follow-up completeness, and a full protocol are not reported in the registry record. These omissions limit reconstruction of how the study was conducted and how its results should be interpreted.

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:

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 Change in the Number of Enhancing Leptomeningeal Foci on 1 Year Follow up Compared to Baseline in MS Patients Treated With Ocrelizumab., measured over 1 year.

The primary endpoint is the change in the number of enhancing leptomeningeal foci on one-year follow-up compared with baseline in MS patients treated with ocrelizumab. It is a count of MRI-visible foci, expressed in the registry as a mean with standard deviation and measured in number of enhancing foci. Leptomeningeal enhancement is the imaging feature being studied as a marker of meningeal inflammation. The registry summary explains the biological rationale: meningeal inflammation may relate to damage in gray matter, and ocrelizumab targets circulating B-cells.

Following the same participants from baseline to follow-up can describe whether the measured imaging feature changes over time. A mean summarizes the average count in the analyzed group, while the standard deviation describes how much individual measurements vary around that average. These are different kinds of information: the mean concerns the group average, and the standard deviation concerns spread across participants. Neither one alone shows how precisely the group change has been estimated.

The registry record does not report the baseline or follow-up means, the mean change, its uncertainty, or a statistical test. It also does not describe image-reading procedures, reproducibility, or the analysis population. Consequently, the endpoint definition is available, but the amount and precision of any observed change cannot be assessed from the registry record. The endpoint is an imaging measure; the record does not establish that a change in this measure corresponds to a change in symptoms, disability, or another clinical outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean count of enhancing leptomeningeal foci, with standard deviation, at one-year follow-up compared with baseline. Several statistical ideas help explain what such an endpoint can show and what information is needed to interpret it. The registry record does not report the actual analysis method, so the explanations below are general rather than a description of methods confirmed to have been used in this study.

What does a mean change describe?

A mean is an average across the observations included in an analysis. For a longitudinal endpoint, the intended comparison concerns measurements at baseline and follow-up. If the same participants contribute measurements at both times, their observations are related: a participant's follow-up value may depend on that participant's baseline value. An analysis that uses the pairing can account for this relationship. Treating related observations as independent can misrepresent uncertainty. The registry record does not state how the repeated measurements were analyzed or whether all analyzed participants had measurements at both time points.

A group mean can make a pattern easier to summarize, but it can hide differences between participants. Some participants may have no enhancing foci, while others may have more, and a few unusually high counts can influence an average. These are general possibilities for count outcomes, not reported features of this study's data. The distribution of observed counts is not reported in the registry record, so it is not possible to determine whether the mean is a representative summary or whether a different model would be more suitable.

What does the standard deviation tell the reader?

The standard deviation describes the spread of individual values around the mean. It is not the same as the uncertainty in the estimated mean change. Uncertainty in an estimate is often expressed with a confidence interval, which conveys a range of values compatible with the observed data under the analysis assumptions. The primary endpoint is described as a mean with standard deviation, but the numerical estimates and a confidence interval are not reported in the registry record. The standard deviation alone would not show how precisely the mean change was estimated.

General statistical practice for repeated measurements also considers the number of paired observations, the amount of within-participant variation, and whether the analysis population is consistent across the time points. If follow-up measurements are absent for some participants, the analyzed set may differ from the enrolled set. How many participants had usable baseline and follow-up scans, how missing scans were handled, and whether the analysis used all available observations are not reported in the registry record.

Why might a count need special attention?

A count is bounded below by zero and may have a distribution unlike a continuous measurement that can take any value on a scale. In general, count data can be skewed, and their variability may increase as the mean increases. Over-dispersion occurs when variation is greater than a simple model assumes; if ignored, standard errors and confidence intervals can be unreliable. Depending on the observed data and study design, analysts may consider count models or other methods that accommodate the distribution. This is a general explanation, not a claim that over-dispersion occurred or that a particular count model was used. The registry record does not report the distribution of foci or the statistical method used.

It also matters whether the target is a difference in average counts, a change in the proportion of participants with any enhancement, or another measure. These targets answer different questions. The primary endpoint targets the number of foci, while a listed secondary outcome concerns the proportion of participants with meningeal enhancement. A count can change even if the proportion with any enhancement does not, and a proportion can change without conveying how many foci are present among affected participants. Numerical results for either outcome are not reported in the registry record.

How should planning illustrations be read?

Planning illustrations are calculations for hypothetical future studies, not observed outcomes and not evidence of the precision achieved in this study. The registry record describes illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. These assumptions describe the calculation framework; they do not establish that the trial itself used equal allocation or that its arms form a valid control comparison. The record states that allocation was not stated and that arms are not a like-for-like control comparison.

The illustrations are described as being computed from an observed effect, but the numerical observed effect is not reported in the registry record. The record also does not report a sample-size justification for the trial's design. Planning values cannot substitute for an analysis of enrolled participants, and they should not be read as observed power. Actual statistical evidence depends on the data, the chosen model, its assumptions, and the uncertainty around the estimated effect. Without endpoint results and an inferential analysis, no conclusion about the precision or strength of evidence can be drawn.

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("Participants With Baseline Meningeal Enhancement")
n   <- c(14)
m   <- c(0.07)
sp  <- c(2.9)
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  Participants With Baseline Meningeal Enhancement  14  0.070  2.900  -1.604  1.744

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but it does not report numerical results for the primary endpoint or the secondary outcome concerning the proportion of participants with meningeal enhancement. It also lists zero analyses. The outcome descriptions alone do not indicate which analyses were performed, which outcomes were emphasized in the final analysis, or whether any result was selected from multiple time points or definitions.

When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently unusual result can increase. Statistical methods may address this issue by prespecifying a primary outcome, adjusting inference, or using a structured testing strategy. This is a general explanation; whether any such approach was used in this study is not reported in the registry record. A multiplicity adjustment, a hierarchy of endpoints, and a complete statistical analysis plan are not reported in the registry record.

Missing data are another essential part of interpretation. A one-year endpoint requires follow-up information, and the record does not state how many participants had a usable follow-up scan, whether anyone withdrew, or how absent measurements were treated. It does not describe imputation, a complete-case approach, or sensitivity analyses. These methods can lead to different interpretations when missingness is related to participants' outcomes, but the pattern of missingness in this study is not reported in the registry record.

The analysis population is also unclear. The registry record does not specify whether the primary endpoint included all enrolled participants, only those treated, only those with baseline enhancement, or participants with complete imaging at both time points. Although the adverse-event entry identifies a group with baseline meningeal enhancement, that entry does not establish the primary endpoint analysis population. Without prespecified analysis populations, outcome results, and missing-data details, neither the analysis denominator nor the robustness of any estimated change can be assessed.

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.

The serious adverse-event entry is for the group titled Participants With Baseline Meningeal Enhancement. It records 14 at risk in the serious-event category and 0 affected. The other-event category also records 14 at risk and 0 affected, and the death count is 0. These are the figures recorded for that group; they should not be extended to participants or treatment exposures that are not described by the entry.

At-risk and affected counts are different quantities. The at-risk figure identifies the group represented in the entry, while the affected figure records how many in that group were reported as affected in the corresponding category. A zero affected count means no affected participants were recorded in that category for this entry. It does not establish that no adverse events occurred outside the group, outside the reporting period, or under other definitions.

The registry record does not provide event terms, event timing, exposure duration, severity details beyond the serious-event classification, or a comparative safety analysis. It also does not clarify how the safety group relates to the primary endpoint population or to the listed intervention. The figures therefore support only a narrow description of the recorded safety entry, not a broad assessment of safety or a comparison of treatments.

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

This study addresses an important measurement question: whether 7T MRI can characterize meningeal enhancement over time in multiple sclerosis. The primary endpoint is a count of enhancing leptomeningeal foci at one-year follow-up compared with baseline among patients described as treated with ocrelizumab. The registry summary supplies a biological rationale involving B-cells and meningeal inflammation. That rationale explains why the question may be of interest; it does not demonstrate that the imaging measure changed or that treatment caused a change.

The registry record does not report the primary endpoint results, a statistical analysis, or a confidence interval. It is therefore not possible to say whether the mean count increased, decreased, or remained similar, or how precisely any change was estimated. The same limitation applies to the listed secondary outcome concerning the proportion of participants with meningeal enhancement. Without numerical findings, the posted results do not establish the direction, magnitude, or statistical uncertainty of an imaging response.

The title refers to predicting response, but prediction requires more than measuring an outcome at follow-up. In general, a prediction analysis needs a clearly defined response target, a model or rule using predictor information, and an evaluation of predictive performance. The registry record does not report those details or results. It therefore cannot establish that meningeal enhancement predicts clinical response to ocrelizumab.

Even an observed MRI change would not by itself demonstrate a change in disability or another patient-centered outcome. A biomarker may be useful for research while still requiring separate evidence about measurement reliability and its relationship to clinically meaningful outcomes. Those validation results are not reported in the registry record. The record also cautions that allocation was not stated and that study arms are not a like-for-like control comparison, so it does not support a straightforward randomized treatment-effect interpretation.

The appropriate reading is limited but useful: the registry identifies a longitudinal imaging endpoint and a hypothesis motivating its study. It does not provide the endpoint results needed to judge whether the MRI measure changed, whether any change was precise, or whether it predicted clinical response. No conclusion that ocrelizumab did or did not produce a benefit follows from the information recorded.

14. Why This Trial Matters Statistically

The statistical interest of this study lies in the use of a quantitative imaging feature as a possible measure of meningeal inflammation. A count of enhancing foci may offer a more specific imaging target than a broad description of MRI appearance. Following the measure from baseline to one-year follow-up also makes the question longitudinal: the aim is to characterize change within the observation period, rather than simply describe a single scan.

That design raises practical statistical questions relevant to biomarker research. Repeated measurements from the same participant are related, count outcomes may have uneven distributions, and image measurement may vary across readers or scans. General methods can account for repeated observations and count distributions, but selecting an appropriate method requires information about the data and measurement process. The registry record does not report those details, the observed outcome distribution, or the analysis used.

The study also illustrates why a biomarker's measurement role and predictive role should be kept distinct. A measure may describe an imaging feature over time without predicting a clinical response. To support prediction, researchers need a defined target and an evaluation of how well the measure predicts it. The title raises this broader ambition, but the registry record does not describe predictive methods or their results.

Finally, the record shows why design and reporting details matter alongside endpoint definitions. The allocation is not stated, the arms are not described as a like-for-like control comparison, and the intervention listing does not clarify its relationship to ocrelizumab. These uncertainties affect how changes could be attributed and compared. Because numerical primary results and analyses are not reported, this record cannot answer the treatment-effect or prediction questions, but it highlights the statistical information required to address them.

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 most direct limitation is that the registry record does not report numerical results for the primary endpoint. Without the baseline and follow-up summaries, estimated change, or uncertainty, readers cannot assess the size or precision of an imaging difference. The record lists zero analyses, so no inferential result is available to clarify whether an observed pattern, if any, is compatible with random variation under a stated model.

The design description also limits causal interpretation. The record states that allocation was not stated and that arms are not a like-for-like control comparison. It does not identify a suitable control group or explain how treatment exposure relates to the comparison. The intervention listing names Gadoteridol, while the title and endpoint refer to ocrelizumab; the registry record does not resolve this ambiguity. As a result, the treatment context is not fully reconstructable from the record.

Other important details are absent. Eligibility criteria, participant characteristics, baseline disease features, imaging acquisition and reading procedures, and follow-up completeness are not reported in the registry record. The record does not specify how missing scans were handled, which participants entered the primary analysis, or whether measurement reliability was evaluated. These details matter because selection into an analysis and variability in imaging assessment can affect the interpretation of a mean change.

The title's predictive aim is not matched by a reported prediction method or performance result. The registry record also does not report a complete statistical analysis plan, multiplicity strategy, or sample-size justification. These gaps prevent assessment of how the analysis was planned and whether the reported outcomes, if later available, would directly address the stated aims. The limitations concern what can be concluded from the registry record; they do not establish what may have been done in unreported study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Meningeal Inflammation on 7T MRI as a Tool for Measuring and Predicting Ocrelizumab Response in Multiple Sclerosis — NCT03396822.
• Registry record last updated 2024-02-28; status last verified 2024-02.
• Results first posted 2024-02-05.
• 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 multiple sclerosis study sponsored by the University of Maryland, Baltimore, with enrollment of 24. It lists a start date of 2018-09-24 and a primary completion date of 2023-05-25. The primary endpoint is the change in the mean number of enhancing leptomeningeal foci at one-year follow-up compared with baseline in MS patients treated with ocrelizumab.

The record lists Gadoteridol as an intervention, but does not explain its relationship to the ocrelizumab-focused endpoint. Allocation is not stated, and the arms are not described as a like-for-like control comparison. The record lists three outcome measures and zero analyses, but numerical primary and secondary outcome results are not reported. Safety figures for the group titled Participants With Baseline Meningeal Enhancement include 0 affected in the serious-event category, 0 affected in the other-event category, and 0 deaths. Overall, the registry defines the imaging question but does not report the results needed to assess change, precision, or prediction.