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 Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) (NCT00213135), a randomized phase 3 study. The primary outcome is Annualized Qualifying Relapse Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00213135 |
| Phase | Phase 3 |
| Condition | Multiple Sclerosis, Relapsing-Remitting |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 1326 |
| Arms in the primary outcome | 3 |
| Lead sponsor | EMD Serono |
| Results posted | Yes |
2. Clinical Question
Population
Participants with relapsing-remitting multiple sclerosis (RRMS) were eligible for the study. The primary endpoint population is described as the intention-to-treat (ITT) population, defined in the registry record as all participants randomized in the study. The record gives an enrollment of 1326.
Intervention
The study compared two oral cladribine dose groups: cladribine 5.25 mg/kg and cladribine 3.5 mg/kg. The record does not provide further arm descriptions.
Comparator
Both cladribine groups were compared with a placebo group. The trial is described as placebo-controlled.
Primary question
At Week 96, how did the annualized qualifying relapse rate in each cladribine group compare with the rate in the placebo group? The endpoint counts qualifying relapses relative to time on study and expresses the result as relapses per year.
The registry describes the study’s purpose as evaluating the safety and efficacy of cladribine tablets in RRMS. The primary question is specifically about the frequency of confirmed qualifying relapses over follow-up, rather than a direct measure of every aspect of disease activity or disability. The qualifying-relapse definition required a specified worsening in functional systems, absence of fever, persistence for at least 24 hours, and preceding clinical stability or improvement. The primary results therefore concern events meeting that operational definition, not every reported symptom or change in health.
The registry also lists secondary questions about the percentage of relapse-free participants, time to disability progression, and magnetic resonance imaging lesion measures. Those outcomes address related but distinct aspects of disease activity and disability. The fact that an outcome is listed does not mean a complete result is available in the registry record.
3. Trial Design
This was a Phase III, randomized, double-blind, three-arm, placebo-controlled, multi-center study with a parallel-group model. The registry describes masking as triple. It records an enrollment of 1326 and lists three groups: cladribine 5.25 mg/kg, cladribine 3.5 mg/kg, and placebo. The arm descriptions are not reported in the registry record.
The study began in 2005-04, had primary completion in 2008-11, and is marked completed. The sponsor is EMD Serono. The record identifies multiple sclerosis, relapsing-remitting, as the condition under study. It does not provide further detail about the centers, how randomization was implemented, or which people were included in the masking designation; those details are not reported in the registry record.
A parallel design assigns participants to a study group and compares outcomes across groups over the study period. Random allocation is intended to support comparability of groups at the outset, although it does not ensure that every measured or unmeasured characteristic is balanced. Masking can reduce some forms of bias in treatment administration, assessment, or reporting, but the registry entry does not describe the operational details needed to assess those protections.
The primary endpoint is specified at Week 96. The primary analysis population is described as ITT, meaning all randomized participants according to the registry’s definition. The record gives group sizes of 456.0 for cladribine 5.25 mg/kg, 433.0 for cladribine 3.5 mg/kg, and 437.0 for placebo in the primary outcome results. The registry does not report whether every randomized participant contributed a measured endpoint value or how missing endpoint data were handled.
The study design establishes the comparison being evaluated, but it does not by itself establish the analysis details. The protocol’s allocation procedures, sample-size justification, planned handling of multiplicity, and any interim analyses 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 | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo |
|---|---|---|---|
| STARTED | 456 | 433 | 437 |
| COMPLETED | 406 | 398 | 380 |
| NOT COMPLETED | 50 | 35 | 57 |
Reasons for not completing this period:
| Reason | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo |
|---|---|---|---|
| Adverse Event | 9 | 5 | 5 |
| Lost to Follow-up | 11 | 8 | 4 |
| Protocol Violation | 4 | 4 | 10 |
| Death | 1 | 1 | 2 |
| Disease progression | 4 | 5 | 21 |
| Other | 21 | 12 | 15 |
Analysis population for the primary outcome, as defined in the registry: The intention-to-treat (ITT) population included all participants who were randomized in the study.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 456 | 433 | 437 | 1326 | |
| Age, Continuous | years | 39.1 (SD 9.9) | 37.9 (SD 10.3) | 38.7 (SD 9.9) | 38.6 (SD 10.0) |
| Sex: Female, Male: Female | Participants | 312 | 298 | 288 | 898 |
| Sex: Female, Male: Male | Participants | 144 | 135 | 149 | 428 |
6. Primary Endpoint
The registry lists the primary outcome as Annualized Qualifying Relapse Rate, measured over Week 96.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | relapses per year |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the annualized qualifying relapse rate at Week 96, expressed as relapses per year. A qualifying relapse was defined by worsening of at least 2 points in at least one EDSS functional system, or at least 1 point in at least two functional systems. Changes in bowel or bladder function or cognition were excluded from those criteria. The change had to occur without fever, last at least 24 hours, and be preceded by at least 30 days of clinical stability or improvement.
The registry states that annualized relapse rate was calculated by dividing the total number of confirmed relapses by the total number of days on study and multiplying by 365.25. This expresses the event count on a yearly scale while accounting for differences in time on study. The endpoint is useful for comparing relapse frequency across groups when participants may contribute different amounts of observed follow-up.
The EDSS assesses disability across 8 functional systems and produces an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis). The relapse definition uses changes in functional-system scores to distinguish qualifying clinical events from changes that do not meet the specified threshold. The endpoint remains a count-based measure of qualifying relapses; it does not directly summarize disability progression, lesion activity, or every possible clinical change.
The registry reports 95% confidence intervals for the group-level annualized rates. These intervals communicate uncertainty around the estimated rates, rather than showing the range of individual participants’ outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At Week 96, the registry reports an annualized qualifying relapse rate of 0.15 for cladribine 5.25 mg/kg, 0.14 for cladribine 3.5 mg/kg, and 0.33 for placebo. The corresponding 95% confidence intervals are 0.12 to 0.17, 0.12 to 0.17, and 0.29 to 0.38. These are estimates of group-level relapse rates under the registry’s qualifying-relapse definition.
The sponsor-reported comparisons give a relative risk of 0.43 for cladribine 5.25 mg/kg versus placebo, with a 95% confidence interval from 0.35 to 0.54, and a relative risk of 0.43 for cladribine 3.5 mg/kg versus placebo, with a 95% confidence interval from 0.34 to 0.54. Both reported p-values are <0.001. The point estimates are below 1, and both confidence intervals are also below 1. In the context of a relative risk, a value of 1 represents equal rates in the two groups; values below 1 indicate a lower estimated rate in the cladribine group than in the placebo group.
The reported p-values indicate that, under the stated Wald chi-square testing approach and the null hypothesis of no relative-rate difference, results at least as incompatible with that null were observed at the reported significance level. A small p-value does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. The confidence intervals add information about statistical precision: they show a range of values compatible with the data and method, rather than a guarantee about the true effect.
The registry’s two reported primary comparisons have the same relative-risk point estimate and similar confidence intervals. The group-level rates likewise show lower estimated rates in both cladribine groups than in the placebo group. These statements describe the posted estimates and their uncertainty; they are not a claim about every participant’s experience or about outcomes outside the measured endpoint and follow-up period.
The primary result should be read alongside the study’s definition of a qualifying relapse, the specified ITT population, and the missing-data information. Although the registry defines the ITT population as all randomized participants, it does not report the detailed analysis implementation or how missing relapse information was treated. That limits the ability to independently assess the influence of incomplete follow-up or other analysis choices.
The statistical comparison does not settle questions about disability progression, imaging findings, longer-term outcomes, or the balance of benefits and harms. Those require their own reported results and suitable interpretation. The primary evidence is specifically about annualized qualifying relapse rates at Week 96, with uncertainty represented by the posted confidence intervals and the sponsor’s reported comparisons.
9. Statistical Methods Explained
The primary outcome is a count-based rate: confirmed qualifying relapses are related to the time participants spent on study and expressed per year. This is different from simply comparing total relapse counts, because participants can have different observation times. Annualization places the rate on a common time scale, using the calculation described in the registry record.
What does the confidence interval convey?
A confidence interval describes the uncertainty around an estimated quantity under the statistical method used. A narrower interval indicates greater precision than a wider interval, all else equal. It is not a range containing most individual participants’ values, and a 95% confidence interval is not a statement that there is a 95% probability the fixed true value lies inside this particular interval. The rate intervals are reported separately for each group, while the relative-risk intervals describe the comparisons between groups.
For the primary endpoint, the registry reports group rates and their 95% confidence intervals. It also reports relative-risk estimates with 95% confidence intervals for each cladribine group compared with placebo. A relative risk compares the estimated rate in one group with the estimated rate in another. A value of 1 corresponds to equal rates; an estimate below 1 indicates a lower estimated rate in the numerator group. The uncertainty interval matters because an estimate alone does not show how precisely the comparison has been determined.
How should the reported test be understood?
The reported analysis method is the Wald chi-square test. In general, a Wald test assesses whether an estimated quantity is sufficiently far from a null value relative to its estimated uncertainty. The registry gives the relative-risk result, confidence interval, and p-value, but does not provide further detail about the model specification, variance estimation, or any adjustment factors. Those details are not reported in the registry record.
A p-value is calculated under a specified null hypothesis and statistical model. It describes how unusual the observed test statistic, or one more extreme, would be if the null hypothesis and model assumptions held. It is not the probability that the result occurred by chance, nor is it a measure of treatment effect size. The registry reports p < 0.001 for each primary comparison; the direction and magnitude of the estimated relative risks and the confidence intervals should be considered alongside those p-values.
Why can count data need special care?
Counts often have a distribution that differs from a symmetric, continuous measurement. In general, count outcomes can be concentrated at low values, and their variability can be greater than a simple model assumes. Over-dispersion is the general term for variability exceeding what a chosen model expects; if it is not addressed appropriately, uncertainty estimates and tests may be unreliable. The posted registry results do not report enough model detail to determine whether or how over-dispersion was assessed for the primary endpoint. This is a general statistical consideration, not a claim that the trial analysis did or did not account for it.
Annualized rates also depend on how event counts and time at risk are defined. The registry defines a qualifying relapse and describes the rate calculation, but does not report finer details about follow-up interruptions, recurrence handling beyond the stated confirmed-relapse count, or any model-based adjustment. Those features should not be inferred from the reported group summaries alone.
What do the secondary calculations represent?
The posted relapse-free participant comparisons are unadjusted recalculations from the reported group summaries. A risk difference is the difference between two proportions; it expresses a contrast on an absolute probability scale. This is a general description of the measure. The posted confidence intervals and p-values for those recalculations are unadjusted, and the registry does not list sponsor-reported analyses for that secondary outcome. They should therefore be distinguished from the sponsor-reported primary analyses.
The available planning illustrations use the observed effect as a reference and show assumptions for detecting a stated fraction of that effect. They are planning illustrations, not observed power and not evidence of the study’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effects considered are 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Such illustrations depend on assumptions about the effect to be detected and the analysis; they do not establish that the original trial was designed using those assumptions.
For a binary outcome, sample-size planning depends on the expected proportions and the target difference. A smaller target effect generally requires more participants for a given power target, all else equal. This is general statistical reasoning and should not be mistaken for an observed trial result. The planning values are not a retrospective measure of the probability that the trial detected an effect.
How should statistical and clinical meaning be separated?
Statistical significance addresses compatibility with a null hypothesis under a model and test. Precision concerns the width of the interval around an estimate. Clinical importance requires interpretation of the size and relevance of the outcome in context, and is not determined by a p-value alone. For this study, the registry provides the endpoint definition, group estimates, confidence intervals, and reported tests, but does not report a threshold for a clinically important difference. That threshold is not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wald Chi-square test | Relative Risk 0.43 | 0.35 to 0.54 | < 0.001 |
| Wald Chi-square test | Relative Risk 0.43 | 0.34 to 0.54 | < 0.001 |
For the primary endpoint, the registry reports sponsor analyses comparing each cladribine group with placebo using a Wald chi-square test. For cladribine 5.25 mg/kg, the reported relative risk is 0.43, with a 95% confidence interval from 0.35 to 0.54 and p < 0.001. For cladribine 3.5 mg/kg, the relative risk is also 0.43, with a 95% confidence interval from 0.34 to 0.54 and p < 0.001. These are the sponsor-reported primary comparisons and should be distinguished from unadjusted recalculations made from posted summary statistics.
The available posted primary group rates and intervals provide descriptive context for those comparisons. No discrepancy is flagged for this record. The registry does not provide enough detail to independently reproduce the primary Wald analyses from the group summaries alone, including all model and variance-estimation choices. The sponsor’s reported analysis is therefore the primary inferential result recorded for this endpoint.
For the relapse-free secondary outcome, the registry lists no sponsor-reported analysis. The comparisons available for that outcome are unadjusted recalculations from group summaries. They offer a separate descriptive comparison, but should not be represented as the sponsor’s own inferential analysis or as an adjustment for the study’s multiple outcomes. The registry record does not report a sponsor analysis for that secondary endpoint.
11. Multiplicity, Missing Data and Analysis Populations
The registry identifies an ITT population for the primary outcome and defines it as all participants randomized in the study. That definition is useful, but the record does not report the detailed analysis implementation, including whether every randomized participant had an observed endpoint measurement or how incomplete follow-up was handled. The missing-data method and the amount or pattern of missing primary outcome data are not reported in the registry record.
Missing outcome information can affect estimates when the probability of being observed is related to outcome status or group assignment. In general, the consequences depend on why data are missing and on the analysis method used. No assumptions about missingness, imputation, censoring, or sensitivity analyses should be inferred from the ITT label alone. Those details are not reported in the registry record.
The primary endpoint contains two cladribine-versus-placebo comparisons. The registry reports both comparisons and their p-values, but a prespecified multiplicity procedure for the pair of comparisons is not reported in the registry record. The entry also lists multiple secondary outcomes. Any adjustment strategy across primary comparisons or across primary and secondary outcomes is not reported in the registry record. Consequently, nominal p-values should be read as the results of the stated comparisons, not as proof that family-wise error was controlled across all outcomes.
The registry lists four outcome measures and two analyses overall, but that count does not describe the full analysis plan or establish how testing across outcomes was handled. Interim analyses and any associated stopping rules are not reported in the registry record. The protocol’s sample-size justification, including its assumptions and target effect, is also not reported in the registry record.
These omissions do not invalidate the posted estimates. They limit what can be independently assessed about robustness, multiplicity, and the effects of missing data. A complete evaluation would require the planned methods and their implementation, including details about analysis populations, missing observations, and any prespecified adjustments.
12. 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 |
|---|---|---|---|
| Cladribine 5.25 mg/kg | 41 | 454 | 9.0% |
| Cladribine 3.5 mg/kg | 36 | 430 | 8.4% |
| Placebo | 28 | 435 | 6.4% |
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 |
|---|---|
| Cladribine 5.25 mg/kg | 324 of 454 |
| Cladribine 3.5 mg/kg | 286 of 430 |
| Placebo | 242 of 435 |
Most frequent serious adverse event terms
| Event term | Organ system | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo |
|---|---|---|---|---|
| Pneumonia | Infections and infestations | 3 of 454 | 3 of 430 | 3 of 435 |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 454 | 3 of 430 | 0 of 435 |
| Lymphopenia | Blood and lymphatic system disorders | 1 of 454 | 3 of 430 | 0 of 435 |
| Cholelithiasis | Hepatobiliary disorders | 2 of 454 | 1 of 430 | 0 of 435 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 454 | 0 of 430 | 1 of 435 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 454 | 1 of 430 | 1 of 435 |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | 1 of 454 | 1 of 430 | 1 of 435 |
| Adnexitis | Infections and infestations | 2 of 454 | 0 of 430 | 0 of 435 |
| Appendicitis | Infections and infestations | 0 of 454 | 0 of 430 | 2 of 435 |
| Pyelonephritis | Infections and infestations | 0 of 454 | 2 of 430 | 0 of 435 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo |
|---|---|---|---|---|
| Headache | Nervous system disorders | 94 of 454 | 104 of 430 | 75 of 435 |
| Lymphopenia | Blood and lymphatic system disorders | 142 of 454 | 92 of 430 | 8 of 435 |
| Nasopharyngitis | Infections and infestations | 58 of 454 | 62 of 430 | 56 of 435 |
| Upper respiratory tract infection | Infections and infestations | 52 of 454 | 54 of 430 | 42 of 435 |
| Nausea | Gastrointestinal disorders | 49 of 454 | 43 of 430 | 39 of 435 |
| Back pain | Musculoskeletal and connective tissue disorders | 39 of 454 | 34 of 430 | 28 of 435 |
| Urinary tract infection | Infections and infestations | 32 of 454 | 23 of 430 | 39 of 435 |
| Influenza like illness | General disorders | 27 of 454 | 34 of 430 | 31 of 435 |
| Diarrhoea | Gastrointestinal disorders | 31 of 454 | 30 of 430 | 29 of 435 |
| Influenza | Infections and infestations | 34 of 454 | 27 of 430 | 27 of 435 |
Serious events with the highest arm-level rate: pneumonia (0.7%), uterine leiomyoma (0.7%), lymphopenia (0.7%), pyelonephritis (0.5%), ankle fracture (0.5%).
The registry reports serious adverse events in 41 of 454 participants in the cladribine 5.25 mg/kg group, 36 of 430 in the cladribine 3.5 mg/kg group, and 28 of 435 in the placebo group. It also reports other adverse events in 324 of 454, 286 of 430, and 242 of 435 participants in those respective groups. These are participant counts with the corresponding at-risk group sizes, not a complete description of event types, duration, severity, or causal attribution.
The listed serious adverse-event terms include pneumonia and uterine leiomyoma at 0.7% each, lymphopenia at 0.7%, and pyelonephritis, ankle fracture, and fall at 0.5% each. The registry entry does not provide arm-specific attribution for these listed percentages in the summarized information. The counts should therefore not be interpreted as comparative rates for individual event terms.
Death counts are not reported in the registry record. The available safety figures alone do not establish whether an event was caused by a study treatment, and they do not describe the full balance of benefits and harms. Differences in raw counts also need the context of group size, follow-up, event definitions, and the safety analysis method.
13. What the Result Does, and Does Not, Mean
The primary result is evidence about the rate of qualifying relapses during the period ending at Week 96, as defined in the registry. The posted group estimates are lower in both cladribine groups than in the placebo group, and the sponsor-reported relative-risk estimates are below 1 with confidence intervals below 1. The reported p-values are <0.001 for both comparisons. These statistics describe the observed comparison and its uncertainty under the reported analysis.
The result does not mean that every participant in a cladribine group experienced fewer relapses, or that every participant was relapse-free. Group-level rates summarize outcomes across participants. The registry’s endpoint definition also means that the result applies to qualifying confirmed relapses, not every symptom, change in function, or possible manifestation of RRMS.
The result does not by itself answer whether disability progression differed, whether lesion activity differed, or how outcomes developed beyond the specified follow-up. Those secondary results are not reported in the registry record. It also does not establish the long-term safety profile or provide a complete account of adverse-event causes and consequences.
A confidence interval reflects uncertainty under the statistical approach used; it is not a guarantee that the true value lies within its bounds. A p-value is not the probability that a result is due to chance or that a hypothesis is true. Statistical evidence, precision, and clinical importance are related but distinct considerations. The registry does not report a threshold for a clinically important difference, so clinical importance cannot be inferred from statistical significance alone.
Interpretation is also limited by details that are not reported in the registry record, including the handling of missing endpoint information, multiplicity procedures, and further model specifications. The conclusions should remain tied to the population definition, endpoint, comparison, and follow-up actually described.
14. Why This Trial Matters Statistically
This trial illustrates how a clinical endpoint can be translated into an estimand that supports comparison across groups. Rather than comparing raw relapse totals alone, the primary outcome expresses confirmed qualifying relapses relative to time on study. That distinction matters when observation time may differ, because a rate and a simple count answer different questions.
It also shows why an effect estimate should be read with its uncertainty. The registry reports group-level rates, relative risks, confidence intervals, and p-values. The relative-risk scale communicates a comparison between groups, while the rates provide the underlying group summaries. The confidence intervals convey precision, and the p-values address compatibility with a null hypothesis under a particular test. None of these measures alone describes the entire clinical meaning of the outcome.
The record also illustrates the difference between sponsor-reported analyses and recalculations from summary data. The primary comparisons are reported by the sponsor with a stated method. The available relapse-free comparisons are unadjusted recalculations, with no sponsor analysis listed. Keeping those sources distinct helps prevent a descriptive or exploratory calculation from being mistaken for a prespecified inferential result.
Finally, the example underscores the value of transparent reporting beyond point estimates. Missing-data handling, multiplicity plans, model details, and sample-size justification affect how confidently readers can assess an analysis. When these details are not reported in the registry record, the appropriate response is to define the limits of interpretation rather than fill gaps with assumptions.
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 registry record contains the primary endpoint definition and posted estimates, but it does not provide the protocol-level detail needed to evaluate every analysis choice. The model specification and variance-estimation details for the reported Wald chi-square tests are not reported in the registry record. It is therefore not possible to reconstruct the sponsor’s primary inferential analysis fully from the listed group summaries.
The entry does not report the handling, extent, or pattern of missing primary outcome data. Although the primary population is defined as ITT, the record does not explain how participants without complete follow-up or endpoint information contributed to the analysis. The impact of any missing data cannot be assessed from the available information.
Multiplicity procedures for the two primary comparisons and the listed secondary outcomes are not reported in the registry record. Detailed results for time to disability progression and lesion measures are also not reported. This prevents a full review of consistency across the outcome set and limits interpretation of the secondary evidence.
The arm descriptions are blank, and the registry does not provide further operational detail on randomization or masking. It does not report interim analyses, stopping rules, or the original sample-size justification. The safety information includes counts and selected event terms, but death counts are not reported in the registry record, and the summarized listing does not provide full event-level context or causal assessment.
These are limitations of the available registry information, not findings that the trial did or did not follow a particular procedure. The posted numerical results can be described as recorded, while the unanswered methodological questions remain unresolved without further documentation.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) — NCT00213135.
- Registry record last updated 2014-02-07; status last verified 2014-01.
- Results first posted 2013-12-02.
- 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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19. Record Summary
NCT00213135 is a completed Phase III, randomized, double-blind, three-arm, placebo-controlled, multi-center parallel study sponsored by EMD Serono. It enrolled 1326 participants with relapsing-remitting multiple sclerosis and compared cladribine 5.25 mg/kg and cladribine 3.5 mg/kg with placebo. The recorded study start is 2005-04, and primary completion is 2008-11.
The primary endpoint was annualized qualifying relapse rate at Week 96 in the ITT population. The registry reports lower group-level rates in both cladribine groups than in placebo, with sponsor-reported relative-risk comparisons of 0.43 and p < 0.001 for each. Interpretation remains specific to the defined relapse endpoint and reported follow-up. The registry does not report several details needed for a complete assessment, including missing-data handling and multiplicity procedures.