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 Neuroprotection With Riluzole Patients With Early Multiple Sclerosis (NCT00501943), a randomized phase 2 study. The primary outcome is MRI Parameter- Percent Brain Volume Change for 2 Years.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00501943 |
| Phase | Phase 2 |
| Condition | Multiple Sclerosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 43 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes patients evaluated within twelve months of a clinically isolated syndrome (CIS) onset. Participants also needed at least 2 silent ovoid T2 bright areas in deep white matter on a clinic brain MRI scan. The condition listed in the record is multiple sclerosis. The study was conducted at the UCSF MS Center, and enrollment was 43 participants.
Intervention
The intervention arm received oral riluzole with Avonex (Interferon beta 1a). The study summary describes riluzole at 50 mg once a day for one month, followed by 50 mg twice daily if the first dose was well tolerated. Avonex was to begin 3 months after the study drug if liver function remained normal.
Comparator
The comparison arm received placebo with Avonex. The study was randomized, double blind, parallel group, and placebo controlled. The arm descriptions therefore distinguish the addition of riluzole or placebo while both arms included Avonex.
Primary question
The primary outcome was MRI-based percent brain volume change per year, summarized as a mean with a 95% confidence interval. MRI assessments were scheduled at Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24. The record reports arm-specific estimates, but no two-arm comparison estimate or analysis result is posted. The available data therefore describe the estimates within each arm rather than establish the magnitude or precision of a treatment contrast.
3. Trial Design
This was a phase 2, randomized, double-blind, parallel-group study with a placebo comparator. It was conducted at a single center, the UCSF MS Center. The registry lists 43 participants enrolled, with 22 in the riluzole arm and 21 in the placebo arm. The study status is completed. The registry summary describes the intended enrollment as forty patients, while the enrollment field records 43.
The study focused on people assessed within twelve months of CIS onset, with MRI evidence of at least 2 silent ovoid T2 bright areas in deep white matter. Participants were assigned to riluzole or placebo in addition to Avonex. The summary describes a one-month period at 50 mg of riluzole or matching placebo once daily, with a move to 50 mg twice daily if tolerated. Avonex was planned to start 3 months after study drug initiation if liver function remained normal.
The primary MRI endpoint was assessed at Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24. The summary says participants would be assessed monthly during the first 12 months and every three months thereafter, for a total study duration of 24-month. The enrollment period was described as lasting six months.
The record lists a study start of 2006-07 and primary completion of 2012-10. It does not report the number of participants who completed every visit, the details of treatment adherence, or the reasons any participants may have stopped study participation. The study is described as randomized and double blind, but details of sequence generation, allocation concealment, and how masking was maintained are not reported in the registry record.
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
| Stage | Riluzole | Placebo |
|---|---|---|
| STARTED | 22 | 21 |
| COMPLETED | 20 | 18 |
| NOT COMPLETED | 2 | 3 |
Analysis population for the primary outcome, as defined in the registry: Multivariate regression model was used as the statistical method of analysis for the study. So data from patients who have not completed the study are also used for statistical analysis.
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.
| Characteristic | Unit | Riluzole | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 22 | 21 | 43 | |
| Age, Continuous | years | 38.2 (SD 9.84) | 32.4 (SD 7.85) | 36 (SD 9.32) |
| Sex: Female, Male: Female | Participants | 17 | 14 | 31 |
| Sex: Female, Male: Male | Participants | 5 | 7 | 12 |
| Region of Enrollment: United States | participants | 22 | 21 | 43 |
6. Primary Endpoint
The registry lists the primary outcome as MRI Parameter- Percent Brain Volume Change for 2 Years, measured over Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change per year |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was MRI Parameter- Percent Brain Volume Change for 2 Years, expressed as percent change per year. Baseline MRI was compared with MRI images collected at later scheduled assessments. The record says brain volume change was measured using SIENAX (Structural Image Evaluation using Normalization of Atrophy-X).
Brain volume is a structural imaging measure. Repeated MRI assessment allows investigators to describe how the measured volume changes over the study period. In general, a percentage-change measure expresses change relative to a reference measurement; the registry identifies Baseline as the MRI reference for comparisons at later timepoints. A negative mean indicates that the measured change was in the decreasing direction relative to that baseline reference.
The posted riluzole-arm mean was -0.862 percent change per year, with a 95% confidence interval from -1.168 to -0.556. The placebo-arm mean was -0.49, with a 95% confidence interval from -0.766 to -0.208. These are arm-specific summaries, not an estimate of the difference between arms. No treatment contrast, adjusted estimate, or associated inferential result is posted, so the estimates alone do not establish whether the arms differed.
The endpoint is one of several measurements in the study. The registry also lists changes in normalized white matter volumes, MS Functional Composite, peripapillary retinal nerve fiber layer thickness, Symbol Digit Modality Test, and normalized grey matter volume as secondary outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome estimates describe mean percent brain volume change per year within each randomized arm. The riluzole arm mean was -0.862, with a 95% confidence interval from -1.168 to -0.556. The placebo arm mean was -0.49, with a 95% confidence interval from -0.766 to -0.208. Both posted means are negative, indicating change in the decreasing direction relative to the baseline MRI reference as described by the endpoint.
The riluzole-arm point estimate is more negative than the placebo-arm point estimate. That observation is a comparison of the posted arm summaries, not a formal estimate of the treatment effect. The registry record does not post a between-arm difference, its confidence interval, or a p-value for the primary endpoint. It also does not report a test of whether the arm estimates differ. The displayed arm-level confidence intervals should not be treated as a substitute for a confidence interval around a direct contrast.
A confidence interval describes uncertainty around an estimated quantity under the statistical approach used. It is not a range that contains every participant's outcome, and it does not by itself establish whether a difference between groups is statistically or clinically important. The record identifies the reported dispersion as a 95% confidence interval, but does not give the full model specification or enough information to independently reconstruct those intervals.
The study description says multivariate regression was used and that data from patients who had not completed the study were also used in statistical analysis. The record does not specify the regression terms, which observations contributed to each estimate, how repeated MRI observations were represented, or how missing measurements were handled. Those details affect the interpretation of an estimate based on serial observations.
The registry lists 22 participants in the riluzole arm and 21 in the placebo arm. These arm counts give context for the estimates but do not show how many observations were available at each MRI visit. The outcome record lists no analysis entries. Accordingly, the posted results support a descriptive reading of the arm means and their reported intervals, not a conclusion about comparative efficacy, precision of a treatment contrast, or statistical significance.
The endpoint is also only one part of the trial record. Five secondary outcomes are listed, but their results are not posted in the information available. The record does not describe how multiple outcomes were accounted for in inferential testing. The primary endpoint estimates should therefore be read alongside the incomplete information on other outcomes and analysis procedures, rather than as a complete account of all study findings.
9. Statistical Methods Explained
The primary outcome is a continuous measure, and the registry reports a mean for each arm. A mean represents the central value of a set of measurements. For continuous outcomes, it can be informative to report both the mean and an interval describing its statistical uncertainty. The registry reports 95% confidence intervals for the arm means, rather than a standard deviation or another measure of participant-to-participant spread.
A confidence interval describes uncertainty in an estimated quantity under the method used to calculate it. In general, narrower intervals indicate greater precision, while wider intervals indicate less precision. The interval does not describe the range of individual outcomes. Here, the endpoint estimates and intervals are arm-specific. Without a direct between-arm estimate and its interval, the precision of the treatment contrast cannot be read from the two arm summaries alone.
What does the regression description tell us?
The registry says a multivariate regression model was used and that data from patients who had not completed the study were also used in statistical analysis. Regression is a general approach for relating an outcome to one or more explanatory variables. The word “multivariate” alone does not identify the exact model, the variables included, or how repeated measurements were handled. Those details are not reported in the registry record.
Because MRI measurements were scheduled at several timepoints, the analysis involves observations collected over time. In general, measurements from the same participant may be related to one another, and a statistical model may need to account for that dependence. The record does not state whether the model included participant-level effects, time effects, treatment-by-time terms, baseline covariates, or another structure. It also does not specify whether the reported mean summarizes change across visits or reflects a particular model-based contrast over follow-up.
How should the reported intervals be read?
The riluzole-arm mean is -0.862, with a 95% confidence interval from -1.168 to -0.556. The placebo-arm mean is -0.49, with a 95% confidence interval from -0.766 to -0.208. These intervals describe uncertainty around the respective means according to the registry’s reported analysis. They do not directly estimate the difference between the two arms. A comparison requires an estimate of that contrast and its uncertainty, neither of which is posted.
In general, a formal comparison also depends on the analysis model and assumptions, not only on the numerical distance between arm means. The registry does not report a p-value or a confidence interval for the treatment contrast, so there is no posted inferential result to interpret for the primary comparison. The record does not indicate whether the analysis was adjusted for baseline values or other characteristics.
Why do missing observations matter?
The description explicitly says that data from patients who had not completed the study were included in statistical analysis. This indicates that the analysis was not restricted, according to the summary, to participants who completed the full study. However, use of some data from non-completers does not reveal how missing measurements were handled. In general, missing-data methods make assumptions about the relationship between missingness and observed or unobserved outcomes. The record does not identify those assumptions or say whether imputation or another missing-data procedure was used.
Repeated MRI observations can be incomplete for different reasons, and the number available may vary by timepoint. The registry does not report visit-specific numbers, reasons for missing MRI assessments, or how many participants contributed to each estimate. It is therefore not possible to evaluate the amount or pattern of missing outcome data from the posted information.
What can planning calculations say?
Any sample-size calculations associated with these results are planning illustrations based on the observed effect under stated assumptions, not the trial’s original design justification. They do not describe observed power. In general, a planning calculation asks how many participants would be needed to detect a specified effect under assumptions about allocation, significance level, and statistical approximation. Such an illustration does not replace the trial’s actual estimate and uncertainty, and it cannot establish that the study was adequately powered for its original question.
The registry record does not report the original sample-size justification, interim analyses, detailed statistical analysis plan, model diagnostics, or multiplicity procedure. These absences limit reconstruction of the analysis and its assumptions. The posted means and confidence intervals remain useful descriptive summaries, but a fuller inferential interpretation would require details not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary MRI outcome and five secondary outcomes: changes in normalized white matter volumes, MS Functional Composite, peripapillary retinal nerve fiber layer thickness, Symbol Digit Modality Test, and normalized grey matter volume. Considering several outcomes can raise the general statistical issue of multiplicity: when multiple hypotheses are tested, the chance of at least one apparently unusual result may increase. The registry record does not report whether the analyses were adjusted for multiple comparisons, whether outcomes were prioritized in a testing hierarchy, or how any secondary findings were intended to be interpreted.
The record identifies the primary analysis method as multivariate regression and says that data from patients who had not completed the study were also used. It does not provide a detailed analysis plan, a definition of the analysis population, or a description of how missing MRI observations were handled. The number of participants contributing measurements at each visit, reasons for missing data, and any imputation approach are not reported in the registry record. Including some available data from non-completers does not by itself explain how incomplete follow-up was addressed.
The registry lists zero analysis entries for the outcome record. It therefore does not post results for the listed secondary outcomes or a direct inferential comparison for the primary endpoint. The absence of posted analyses should not be read as evidence that no analyses were conducted; it means that their methods and results are not reported in the registry record. Information on interim analyses, adjustments for multiple testing, and analysis-population definitions is also not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Riluzole | 0 | 22 | 0.0% |
| Placebo | 0 | 21 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Riluzole | 15 of 22 |
| Placebo | 15 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Riluzole | Placebo |
|---|---|---|---|
| dizziness | Ear and labyrinth disorders | 9 of 22 | 5 of 21 |
| Nausea | Gastrointestinal disorders | 2 of 22 | 7 of 21 |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | 2 of 22 | 1 of 21 |
| Elevated liver function tests | Hepatobiliary disorders | 2 of 22 | 1 of 21 |
| Dysuria | Renal and urinary disorders | 0 of 22 | 1 of 21 |
The registry lists 0 serious adverse events among 22 participants at risk in the riluzole arm and 0 among 21 participants at risk in the placebo arm. These are the posted serious-event counts for the reported groups. The record does not list any serious adverse-event terms, and deaths are not reported in the registry record.
The record also lists 15 participants with other adverse events among 22 at risk in the riluzole arm and 15 among 21 at risk in the placebo arm. These counts are distinct from the serious adverse-event counts. The registry entry does not provide event-level descriptions, severity breakdowns for the other events, timing, or an attribution assessment for these figures.
Adverse-event counts describe what was recorded in the trial arms; they do not, by themselves, show whether an event was caused by study treatment. A zero posted count does not establish that an event is impossible, and the registry record does not provide enough detail to evaluate the completeness or duration of safety follow-up. These figures should be read as the safety information posted for the trial, not as a complete characterization of risks.
12. What the Result Does, and Does Not, Mean
The posted primary outcome results show negative mean percent brain volume change per year in both arms. The riluzole-arm mean was -0.862, with a 95% confidence interval from -1.168 to -0.556. The placebo-arm mean was -0.49, with a 95% confidence interval from -0.766 to -0.208. These statistics describe arm-specific estimates from the trial’s MRI endpoint.
The riluzole estimate is more negative than the placebo estimate, but that descriptive ordering is not a reported treatment-effect estimate. No between-arm contrast, confidence interval for a contrast, or p-value is posted for the primary outcome. The results therefore do not establish the size or precision of a difference between treatment strategies. They also do not determine whether any difference would be clinically important.
In general, a study result is interpreted in light of its design, analysis methods, outcome measurement, uncertainty, and the population studied. This trial enrolled people described as being within twelve months of CIS onset and having a specified MRI feature. Its results should not automatically be generalized to people outside that registry-defined population. The record does not report enough information to assess representativeness or differences between enrolled participants and other populations.
The registry lists five secondary outcomes, but their results are not posted in the outcome information. Nor does the record report how missing measurements or multiple outcomes were addressed. These gaps constrain any broad account of the findings. The posted estimates are best understood as summaries of the MRI outcome in each arm, with the reported uncertainty, rather than proof for or against a treatment effect.
The serious adverse-event counts are 0 in each arm, while the record lists 15 participants with other adverse events in each arm. Those figures provide limited descriptive safety information and do not establish attribution, comparative risk, or the absence of unreported events. No medical conclusion should be drawn from the posted summaries alone.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized comparison and a reported treatment contrast are not the same thing. Randomization defines the intended comparison between riluzole plus Avonex and placebo plus Avonex. The posted primary outcome results, however, are means for each arm rather than an estimate of the difference between them. A direct contrast with its uncertainty is needed to quantify the comparative result in a way that corresponds to the randomized question.
The record also shows the value of keeping uncertainty visible. Each arm mean is accompanied by a 95% confidence interval, which indicates that an estimate is not a perfectly precise description of the underlying quantity. Interpreting these intervals appropriately requires knowing what they estimate and how they were derived. The registry identifies multivariate regression but does not report enough model detail to reconstruct the method.
Serial MRI measurements add another statistical consideration: observations from a participant over time may be related. General methods for repeated observations account for that structure, but the registry does not specify how this was done. Likewise, the statement that data from patients who had not completed the study were used is informative, but it does not explain the handling or pattern of missing measurements.
Finally, the record lists several secondary outcomes without posting their results or describing a multiplicity strategy. This makes clear that a single primary endpoint estimate is not a complete account of a trial with multiple outcomes. The trial is therefore a useful example of how registry summaries can offer meaningful descriptive evidence while leaving important questions about comparative inference and analysis details unresolved.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation for interpretation is that the registry posts arm-specific primary outcome means and confidence intervals, but not a direct comparison between arms. There is no posted treatment contrast, contrast confidence interval, or p-value for the primary endpoint. Consequently, the comparative effect and its precision cannot be determined from the reported means alone.
The statistical description is brief. It identifies multivariate regression and says data from patients who had not completed the study were included, but does not report the model specification, covariates, approach to repeated measurements, baseline adjustment, or missing-data method. Visit-specific MRI counts, reasons for incomplete observations, and the number contributing to each estimate are not reported in the registry record.
The registry lists five secondary outcomes but no analysis entries. Their results are not posted, and the record does not explain whether or how multiplicity was handled. The original sample-size justification, interim analyses, and detailed statistical analysis plan are not reported in the registry record. The planning illustrations based on the observed effect do not provide the missing design rationale and are not observed power.
The entry also provides limited detail on study conduct. It describes a randomized, double-blind, parallel design at a single center, but the methods for sequence generation, allocation concealment, and maintaining masking are not reported. Participant completion, treatment adherence, and reasons for discontinuation are not given. The safety entry has limited event detail, with no serious-event terms listed and deaths not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neuroprotection With Riluzole Patients With Early Multiple Sclerosis — NCT00501943.
- Registry record last updated 2014-04-09; status last verified 2014-03.
- Results first posted 2014-04-09.
- 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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18. Record Summary
The registry record describes NCT00501943, a completed phase 2 randomized, double-blind, parallel-group study sponsored by the University of California, San Francisco. The study compared riluzole plus Avonex with placebo plus Avonex in people with early multiple sclerosis, with 43 participants enrolled. The study start was 2006-07, and primary completion was 2012-10.
The primary endpoint was mean MRI percent brain volume change per year, measured using SIENAX at Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24. The posted arm means were -0.862 for riluzole and -0.49 for placebo, each with a 95% confidence interval. No direct comparison result is posted. Five secondary outcomes are listed, but their results are not included in the outcome information. The registry describes multivariate regression and use of data from patients who had not completed the study, while detailed analysis and missing-data methods are not reported in the registry record.