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 A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis (NCT00883337), a randomized phase 3 study. The primary outcome is Core Treatment Period: Overview of Failures.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00883337 |
| Phase | Phase 3 |
| Condition | Multiple Sclerosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 324 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled participants with relapsing multiple sclerosis. Its primary analysis population was the intent-to-treat population: all randomized participants, analyzed in the group to which they were assigned regardless of which drug they actually received. The registry record reports enrollment of 324 participants. The record does not give further eligibility details in the information available for this analysis, so characteristics such as disease duration, prior treatment, or baseline disability are not described.
Intervention
The study compared teriflunomide with interferon beta-1a during the core treatment period. The teriflunomide regimens were 7 mg once daily or 14 mg once daily. In the extension, participants assigned to either teriflunomide regimen received 14 mg once daily. This makes the core-period comparison the clearest place to interpret the randomized dose regimens; extension treatment followed different prior-treatment paths.
Comparator
The comparator was interferon beta-1a, administered 3 times a week during the core treatment period. In the extension, participants previously assigned to interferon beta-1a received teriflunomide 14 mg once daily. The registry record describes the study as randomized, parallel-group, and rater-blinded. It does not report further details about who was masked or how masking was maintained.
Primary question
The primary objective was to assess effectiveness using time to failure: the time until the first confirmed relapse or permanent treatment discontinuation for any cause, whichever came first. The registry also lists secondary assessments of relapse frequency, fatigue, treatment satisfaction, and safety and tolerability. Numerical primary-outcome results are not reported in the registry record, so the relative time to failure among the randomized regimens cannot be quantified from these registry entries.
3. Trial Design
This was a phase 3, randomized, parallel-group study sponsored by Sanofi. The registry record lists enrollment of 324 participants with multiple sclerosis and describes the target population as people with relapsing multiple sclerosis. The study started in 2009-04, reached primary completion in 2011-09, and is listed as completed. These dates describe the registry record; they do not, by themselves, establish the duration of follow-up for an individual participant.
The core treatment period compared teriflunomide 7 mg once daily, teriflunomide 14 mg once daily, and interferon beta-1a 3 times a week. The study used a common core-period end date defined as 48 weeks after the last participant was randomized. The primary endpoint timeframe is described as between 48 and 118 weeks, depending on when a participant enrolled. Thus, participants could have different lengths of observation in the core period even though the end date was common across the trial.
The protocol also included an optional long-term extension until teriflunomide became commercially available in accordance with local regulations. During the extension, participants in all listed treatment paths received teriflunomide 14 mg once daily, with the preceding core-period assignment differing across paths. Extension results therefore address continued treatment under those paths, not a continuation of the original randomized comparison of teriflunomide against interferon beta-1a.
The registry describes randomization and single masking; the official title characterizes the study as rater-blinded. The record does not report the allocation method, concealment procedures, or additional masking details. It also does not report a statistical analysis plan or the rationale for the enrollment target.
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: Randomization was stratified by country and baseline disability (Expanded Disability Status Scale \[EDSS\] score ≤3.5 or \>3.5). Assignment to groups was done centrally using an Interactive Voice Response System (IVRS\] in a 1:1:1 ratio after confirmation of the selection criteria. 324 participants were randomized at 53 sites.
Core Treatment Period
| Stage | Teriflunomide 7 mg/14 mg | Teriflunomide 14 mg/14 mg | IFN-β-1a / Teriflunomide 14 mg |
|---|---|---|---|
| STARTED | 109 | 111 | 104 |
| Treated | 109 | 111 | 101 |
| COMPLETED | 89 | 89 | 71 |
| NOT COMPLETED | 20 | 22 | 33 |
Reasons for not completing this period:
| Reason | Teriflunomide 7 mg/14 mg | Teriflunomide 14 mg/14 mg | IFN-β-1a / Teriflunomide 14 mg |
|---|---|---|---|
| Adverse Event | 9 | 12 | 22 |
| Lack of Efficacy | 7 | 4 | 2 |
| Lost to Follow-up | 1 | 1 | 0 |
| Withdrawal by Subject | 2 | 2 | 6 |
| Wish to be pregnant | 1 | 2 | 1 |
| Poor compliance to protocol | 0 | 0 | 1 |
| Other than above | 0 | 1 | 1 |
Extension Treatment Period
| Stage | Teriflunomide 7 mg/14 mg | Teriflunomide 14 mg/14 mg | IFN-β-1a / Teriflunomide 14 mg |
|---|---|---|---|
| STARTED | 89 | 89 | 59 |
| COMPLETED | 61 | 66 | 40 |
| NOT COMPLETED | 28 | 23 | 19 |
Reasons for not completing this period:
| Reason | Teriflunomide 7 mg/14 mg | Teriflunomide 14 mg/14 mg | IFN-β-1a / Teriflunomide 14 mg |
|---|---|---|---|
| Adverse Event | 8 | 5 | 5 |
| Lack of Efficacy | 8 | 8 | 8 |
| Poor compliance to protocol | 1 | 1 | 1 |
| Lost to Follow-up | 1 | 0 | 0 |
| Other than above | 10 | 9 | 5 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: all randomized participants. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.
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 | Teriflunomide 7 mg / 14 mg | Teriflunomide 14 mg/14 mg | IFNβ1a / Teriflunomide 14 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 109 | 111 | 104 | 324 | |
| Age, Continuous | years | 32.5 (SD 9.2) | 36.8 (SD 10.3) | 37.0 (SD 10.6) | 36.3 (SD 10.0) |
| Sex: Female, Male: Female | Participants | 70 | 78 | 71 | 219 |
| Sex: Female, Male: Male | Participants | 39 | 33 | 33 | 105 |
| Region of enrollment: North America | participants | 8 | 6 | 7 | 21 |
| Region of enrollment: Eastern Europe | participants | 39 | 41 | 35 | 115 |
| Region of enrollment: Western Europe* | participants | 62 | 64 | 62 | 188 |
| Time since first diagnosis of Multiple Sclerosis [MS] | years | 3.72 (SD 5.19) | 3.68 (SD 6.24) | 3.82 (SD 5.69) | 3.74 (SD 5.71) |
| Number of MS relapses: Within the past year | relapses | 1 (0 to 3) | 1 (0 to 4) | 1 (0 to 5) | 1 (0 to 5) |
| Number of MS relapses: Within the past 2 years | relapses | 2 (0 to 4) | 2 (0 to 4) | 2 (0 to 6) | 2 (0 to 6) |
| Time since most recent MS relapse onset | months | 9.00 (SD 13.96) | 7.90 (SD 10.34) | 9.79 (SD 10.72) | 8.88 (SD 11.79) |
| MS subtype: Relapsing Remitting | participants | 109 | 108 | 104 | 321 |
| MS subtype: Secondary Progressive | participants | 0 | 1 | 0 | 1 |
| MS subtype: Progressive Relapsing | participants | 0 | 2 | 0 | 2 |
| Baseline EDSS score: ≤3.5 | participants | 96 | 95 | 93 | 284 |
| Baseline EDSS score: >3.5 | participants | 13 | 16 | 11 | 40 |
6. Primary Endpoint
The registry lists the primary outcome as Core Treatment Period: Overview of Failures, measured over Core treatment period between 48 and 118 weeks depending on when the participant was enrolled.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was time to failure during the core treatment period. Failure was defined as the first occurrence of either a confirmed relapse or permanent discontinuation of treatment for any cause, whichever occurred first. A participant with neither event was considered free of failure. This is a composite endpoint: it combines a clinical event with a treatment-discontinuation event, and either can determine when failure is counted.
A relapse was defined as the appearance or worsening of a clinical symptom that had been stable for at least 30 days and persisted for a minimum of 24 hours in the absence of fever. Confirmation required an increase in the Expanded Disability Status Scale score or Functional System scores. These criteria distinguish the endpoint event from a symptom change that does not meet the registry’s definition.
Time-to-event endpoints are generally used when the timing of an event matters and participants may be observed for different lengths of time. They can incorporate information about when an event occurs, rather than only whether it occurred by a fixed point. In this study, the core-period timeframe varied between 48 and 118 weeks depending on enrollment, making timing relevant to the stated objective. However, the posted primary outcome is titled an overview of failures and the registry entries do not give numerical time-to-failure estimates, event counts by treatment, or a treatment-effect estimate. The endpoint definition can therefore be explained, but the comparative primary result cannot be reconstructed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes an effectiveness comparison centered on time to failure, with failure defined as confirmed relapse or permanent treatment discontinuation for any cause. That definition is important to interpretation because the composite can be triggered by either component. A difference in the endpoint, if reported, would not by itself show whether the difference arose from relapses, discontinuations, or both. Component-specific results would be needed to separate those explanations.
The registry record does not report numerical results for the primary endpoint. It therefore does not establish the number of failures in each randomized group, the distribution of time to failure, or the estimated contrast between treatments. No confidence interval or significance test for the primary comparison is present in the registry record. Without such results, the direction, size, and precision of a treatment difference cannot be described. The trial’s objective and design should not be mistaken for evidence of an observed outcome.
The registry lists secondary outcomes for annualized relapse rate, change from baseline in the Fatigue Impact Scale total score, Treatment Satisfaction Questionnaire for Medication scores, and adverse events. It also lists annualized relapse rate and adverse-event assessments in the extension. The outcome names indicate what was assessed, but numerical results for these outcomes are not included in the registry entries used for this explanation. The presence of an outcome in a registry is not a result, and no conclusion about those measures follows from their listing alone.
Safety information is available for serious and other adverse events in the core treatment period and extension. The posted counts should be read within their named treatment periods and groups, not as a direct comparison of treatment effects. The extension groups reflect different preceding treatment paths, and their observation periods and denominators should not be assumed identical to those in the core period. Death figures are not reported in the registry record.
In general, estimates are more informative when read alongside uncertainty intervals and the analysis population. A confidence interval describes a range of values compatible with the data and analysis under its assumptions; it is not a guarantee that the true effect lies in that interval. No such primary-effect estimate or interval is available in the registry record. As a result, statistical precision and clinical importance of the primary comparison cannot be assessed. The defensible interpretation is limited to the study’s design, endpoint definition, and the adverse-event counts and terms that the registry lists.
9. Statistical Methods Explained
The registry identifies the primary outcome as an overview of failures, with the primary objective framed as time to failure. It does not report the numerical primary results or the detailed statistical methods used for that endpoint. The explanations below describe general statistical concepts relevant to the listed outcomes; they do not assert that a particular unreported method was used.
What does a time-to-event analysis describe?
General: Time-to-event methods use both whether an event occurred and how long participants were observed before the event or the end of follow-up. A participant who has not experienced the event by the last observation is often treated as censored: the observation contributes information up to that point without being treated as an event. The exact handling of censoring, discontinuation, and incomplete follow-up depends on the analysis plan. Those details are not reported in the registry record for this trial.
The endpoint is composite. Its event time is the earlier of confirmed relapse and permanent discontinuation for any cause. That definition makes the endpoint operationally clear, but interpretation of a combined estimate depends on its components. General: a composite may be driven more by one component than another, so component-specific counts and estimates help explain what contributes to the overall result. Those primary component results are not reported in the registry record.
How should the annualized relapse rate be understood?
The registry lists annualized relapse rate estimates using Poisson regression for both the core and extension treatment periods. General: Poisson regression is commonly used for count outcomes, with a time-at-risk term when participants contribute different amounts of observation time. Annualizing expresses a rate on a yearly scale; it is not simply a count of participants who relapsed. The fit of a Poisson model can be affected when the variability in counts is greater than the model expects. General methods may address over-dispersion, but the model specification and any such adjustment are not reported in the registry record. No numerical relapse-rate estimates are available in the registry record.
What do the fatigue and satisfaction outcomes measure?
The listed fatigue outcome is change from baseline in the Fatigue Impact Scale total score. The registry also lists Treatment Satisfaction Questionnaire for Medication scores. General: a change-from-baseline analysis compares a follow-up measurement with a participant’s baseline measurement, while a treatment-satisfaction score represents responses on a questionnaire scale. Interpretation depends on the scale definition, the analysis time point, how missing questionnaire items are handled, and the model used. Those details and the numerical results are not reported in the registry record.
How should confidence intervals and significance tests be read?
General: a confidence interval communicates uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater statistical precision than a wider interval, while the interval’s location indicates which effect values are compatible with the data at the stated confidence level. A p-value evaluates how inconsistent the observed data are with a specified null model; it does not measure the probability that a treatment works or that the null hypothesis is true. The registry entries do not include primary estimates, confidence intervals, or p-values, so none can be interpreted for the primary comparison.
What do the planning illustrations mean?
General: a sample-size planning illustration asks how many participants per arm might be needed under chosen assumptions for a specified power and effect size. It is not an observed trial result and is not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated planning approach uses a total number of events. These are planning assumptions, not evidence that the original trial used them. The registry record does not report the trial’s sample-size justification, and numerical planning outputs are not included in the registry record.
Overall, the registry identifies several outcome types but does not provide enough numerical results or methods detail to reproduce or assess the primary analysis. Statistical explanations of the listed methods should therefore remain general rather than being attributed as confirmed analysis procedures for this study.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a primary endpoint alongside multiple secondary outcomes: relapse rate, fatigue, treatment satisfaction, and adverse events, with some measures also listed for the extension. It compares two teriflunomide dose regimens with interferon beta-1a in the core period. When a study evaluates multiple outcomes or treatment contrasts, the chance of at least one apparently notable finding can increase if each is tested separately without an appropriate strategy. General approaches can include prespecifying a hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any multiplicity strategy was prespecified or applied.
The primary analysis population is described as all randomized participants, analyzed according to randomized assignment regardless of the drug actually received. This is an intent-to-treat definition. The record does not state how participants with missing endpoint information were handled, how censoring was treated, or whether sensitivity analyses were conducted. Missing-data methods can affect estimates when outcome availability is related to treatment or participant outcomes; the direction and extent of any effect cannot be assessed without details.
The registry does not report the statistical analysis plan, analysis populations for the secondary outcomes, or procedures for handling missing questionnaire values. It also does not report interim analyses or stopping rules. These omissions do not show that such procedures were absent; they mean the procedures are not reported in the registry record. The reported endpoint definitions and listed analyses alone are insufficient to determine the full prespecified testing framework or how selective reporting was controlled.
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 |
|---|---|---|---|
| Core Treatment Period: Teriflunomide 7 mg | 12 | 110 | 10.9% |
| Core Treatment:Teriflunomide 14 mg | 6 | 110 | 5.5% |
| Core Treatment: IFN-β-1a | 7 | 101 | 6.9% |
| Extended Treatment: Teriflunomide 14 mg (After 7 mg) | 9 | 90 | 10.0% |
| Extended Treatment: Teriflunomide 14 mg (After 14 mg) | 13 | 88 | 14.8% |
| Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) | 12 | 59 | 20.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Core Treatment Period: Teriflunomide 7 mg | 85 of 110 |
| Core Treatment:Teriflunomide 14 mg | 92 of 110 |
| Core Treatment: IFN-β-1a | 92 of 101 |
| Extended Treatment: Teriflunomide 14 mg (After 7 mg) | 72 of 90 |
| Extended Treatment: Teriflunomide 14 mg (After 14 mg) | 65 of 88 |
| Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) | 48 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Core Treatment Period: Teriflunomide 7 mg | Core Treatment:Teriflunomide 14 mg | Core Treatment: IFN-β-1a | Extended Treatment: Teriflunomide 14 mg (After 7 mg) | Extended Treatment: Teriflunomide 14 mg (After 14 mg) | Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) |
|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 3 of 110 | 1 of 110 | 1 of 101 | 2 of 90 | 0 of 88 | 0 of 59 |
| Tuberculosis | Infections and infestations | 0 of 110 | 1 of 110 | 0 of 101 | 1 of 90 | 1 of 88 | 0 of 59 |
| Cellulitis | Infections and infestations | 1 of 110 | 0 of 110 | 0 of 101 | 1 of 90 | 0 of 88 | 0 of 59 |
| Suicide attempt | Psychiatric disorders | 0 of 110 | 0 of 110 | 0 of 101 | 0 of 90 | 1 of 88 | 1 of 59 |
| Optic neuritis | Nervous system disorders | 1 of 110 | 0 of 110 | 0 of 101 | 1 of 90 | 0 of 88 | 0 of 59 |
| Cholecystitis | Hepatobiliary disorders | 0 of 110 | 0 of 110 | 1 of 101 | 0 of 90 | 0 of 88 | 1 of 59 |
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | 0 of 110 | 0 of 110 | 1 of 101 | 0 of 90 | 0 of 88 | 1 of 59 |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | 0 of 110 | 1 of 110 | 0 of 101 | 0 of 90 | 0 of 88 | 1 of 59 |
| Appendicitis perforated | Infections and infestations | 0 of 110 | 0 of 110 | 0 of 101 | 0 of 90 | 1 of 88 | 0 of 59 |
| Bacterial pyelonephritis | Infections and infestations | 0 of 110 | 0 of 110 | 0 of 101 | 0 of 90 | 1 of 88 | 0 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Core Treatment Period: Teriflunomide 7 mg | Core Treatment:Teriflunomide 14 mg | Core Treatment: IFN-β-1a | Extended Treatment: Teriflunomide 14 mg (After 7 mg) | Extended Treatment: Teriflunomide 14 mg (After 14 mg) | Extended Treatment: Teriflunomide 14 mg (After IFN-β-1a) |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 26 of 110 | 24 of 110 | 17 of 101 | 11 of 90 | 9 of 88 | 3 of 59 |
| Headache | Nervous system disorders | 23 of 110 | 17 of 110 | 26 of 101 | 5 of 90 | 3 of 88 | 10 of 59 |
| Diarrhoea | Gastrointestinal disorders | 19 of 110 | 17 of 110 | 9 of 101 | 10 of 90 | 15 of 88 | 8 of 59 |
| Alanine aminotransferase increased | Investigations | 12 of 110 | 9 of 110 | 30 of 101 | 5 of 90 | 8 of 88 | 2 of 59 |
| Influenza like illness | General disorders | 4 of 110 | 4 of 110 | 49 of 101 | 2 of 90 | 0 of 88 | 6 of 59 |
| Back pain | Musculoskeletal and connective tissue disorders | 10 of 110 | 11 of 110 | 7 of 101 | 5 of 90 | 6 of 88 | 5 of 59 |
| Paraesthesia | Nervous system disorders | 14 of 110 | 11 of 110 | 8 of 101 | 3 of 90 | 2 of 88 | 3 of 59 |
| Upper respiratory tract infection | Infections and infestations | 8 of 110 | 11 of 110 | 9 of 101 | 2 of 90 | 5 of 88 | 3 of 59 |
| Alopecia | Skin and subcutaneous tissue disorders | 6 of 110 | 22 of 110 | 1 of 101 | 4 of 90 | 1 of 88 | 4 of 59 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 11 of 110 | 7 of 110 | 4 of 101 | 6 of 90 | 4 of 88 | 4 of 59 |
Serious events with the highest arm-level rate: alanine aminotransferase increased (2.7%), appendicitis (1.7%), bacterial infection (1.7%), meningitis bacterial (1.7%), pyelonephritis acute (1.7%).
The registry reports serious adverse events and other adverse events separately for named treatment periods and groups. In the core period, the serious-event entries are 12 of 110 for teriflunomide 7 mg, 6 of 110 for teriflunomide 14 mg, and 7 of 101 for interferon beta-1a. The corresponding other-adverse-event entries are 85 of 110, 92 of 110, and 92 of 101. These are the posted affected-participant counts and denominators; they should not be combined across groups or periods.
For the extension, the serious-event entries are 9 of 90 after teriflunomide 7 mg, 13 of 88 after teriflunomide 14 mg, and 12 of 59 after interferon beta-1a. Other-adverse-event entries are 72 of 90, 65 of 88, and 48 of 59, respectively. These extension paths differ by prior core treatment, so they are not a continuation of the original randomized comparison between teriflunomide and interferon beta-1a.
The registry lists alanine aminotransferase increased at 2.7%, and appendicitis, bacterial infection, meningitis bacterial, pyelonephritis acute, and suicide attempt at 1.7% each among the serious terms. The record does not provide the denominators or group attribution for these terms in the registry record. Death figures are not reported in the registry record. Adverse-event counts describe events recorded during the stated periods; without comparable exposure, uncertainty estimates, and further clinical context, they should not be treated as a stand-alone measure of comparative safety.
12. What the Result Does, and Does Not, Mean
The results that can be interpreted from the registry entries are limited. The trial was designed to compare teriflunomide regimens with interferon beta-1a in participants with relapsing multiple sclerosis. Its primary question concerned time to a composite failure event, defined as confirmed relapse or permanent treatment discontinuation for any cause. The registry entries do not include numerical results for that endpoint, so they do not support a statement about which randomized group had a longer time to failure or how large or precise any difference was.
The record does contain adverse-event counts for the core and extension periods and a list of serious adverse-event terms with percentages. Those observations describe what was recorded in the named groups and periods. They do not, on their own, establish that one regimen has a higher or lower risk than another. Such a comparison would require careful attention to the populations, duration of observation, event definitions, uncertainty, and analysis methods. Extension comparisons also involve different prior treatment paths, so the original randomized contrast should not be carried forward as if it were unchanged.
General: statistical significance, if reported, would address compatibility with a null model under specified assumptions; it would not by itself establish clinical importance. Conversely, a non-significant result would not prove that treatments are equivalent. Equivalence or noninferiority requires an appropriate design and prespecified margin. The registry record does not provide the primary estimates or analysis details needed to assess these possibilities.
The record also cannot establish how representative the participants were of people outside the trial, what the results mean for individual treatment decisions, or whether a particular treatment is appropriate. The study objective and posted safety information are not medical advice. The reliable conclusion is narrower: the registry describes the trial question and endpoint and records adverse events, while the numerical primary efficacy comparison and several analysis details are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises several important statistical issues in a setting where outcomes can be observed over different lengths of time. The core treatment period ended on a common date defined relative to randomization of the last participant, and the primary endpoint timeframe is stated as between 48 and 118 weeks depending on enrollment. A time-to-event question is therefore distinct from a simple comparison of event counts at a single shared follow-up point. The timing of events and the handling of participants without an event by the end of observation matter to the analysis.
The endpoint also combines confirmed relapse with permanent treatment discontinuation for any cause. This can provide a broader measure of treatment failure, but its interpretation depends on the contributions of both components. A result for the composite alone would not identify which component drove a difference. The registry’s definition makes that issue especially relevant because discontinuation may occur for reasons other than relapse.
The randomized core-period comparison and the optional extension answer different questions. In the extension, everyone in the listed paths received teriflunomide 14 mg once daily, but prior treatment differed. Those data can describe outcomes during extension treatment, yet do not preserve the original randomized comparison in the same way as the core period. This distinction is central to avoiding misleading cross-period comparisons.
Finally, the registry lists several secondary outcomes but does not report a multiplicity strategy or numerical primary results in the registry record. That limits the ability to judge the strength and precision of the study’s main statistical evidence. The trial is statistically notable for the endpoint structure and follow-up design it describes, while the available record details do not permit a complete assessment of comparative effectiveness.
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 main limitation for interpreting effectiveness is that numerical primary-outcome results are not reported in the registry record. The failure definition and analysis population are described, but there are no group-specific primary event counts, time-to-event estimates, treatment contrasts, confidence intervals, or p-values in the registry record. The primary comparison’s direction and precision therefore cannot be evaluated.
The registry record also does not report the statistical analysis plan, sample-size justification, allocation procedures, concealment details, interim analyses, or missing-data methods. The record describes randomization and single masking, and the official title calls the study rater-blinded, but further masking details are not reported. These gaps prevent a full assessment of potential bias and the prespecification of analyses.
The core follow-up timeframe varies between 48 and 118 weeks depending on enrollment. The record does not provide participant-level observation times or enough detail to assess censoring. The primary endpoint is composite, so the absence of component-specific primary results also limits interpretation. In addition, extension treatment follows different core-period assignments and should not be treated as the same randomized contrast as the core period.
Safety counts are reported for named groups and periods, but the registry entries do not give uncertainty estimates or exposure-adjusted comparisons. The listed serious-event terms are not attributed to a treatment group in the available information, and death figures are not reported in the registry record. These limitations constrain comparative interpretation without establishing that the underlying study or registry contains no further information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis — NCT00883337.
- Registry record last updated 2016-06-13; status last verified 2016-05.
- Results first posted 2012-11-06.
- 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 NCT00883337, a completed phase 3 randomized, parallel-group study sponsored by Sanofi. It enrolled 324 participants with multiple sclerosis and compared teriflunomide 7 mg once daily, teriflunomide 14 mg once daily, and interferon beta-1a 3 times a week during the core treatment period. The trial started in 2009-04 and reached primary completion in 2011-09.
The primary outcome was time to failure, where failure meant the first confirmed relapse or permanent treatment discontinuation for any cause. The primary analysis population was intent-to-treat. An optional extension used teriflunomide 14 mg once daily across the listed prior-treatment paths.
The registry lists secondary outcomes and adverse-event findings, but numerical results for the primary endpoint are not reported in the registry record. The posted safety counts should be interpreted within their specified treatment periods and groups.