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 Study of Efficacy and Safety of Drugs BCD-033 and Rebif for Treatment of Patients With Multiple Sclerosis (NCT02727907), a randomized phase 2, phase 3 study. The primary outcome is Number of Combined Unique Active Lesions.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02727907 |
| Phase | Phase 2, Phase 3 |
| Condition | Multiple Sclerosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 163 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Biocad |
| Results posted | Yes |
2. Clinical Question
Population
People with relapsing-remitting multiple sclerosis. The registry lists multiple sclerosis as the condition and describes the study population in its official title as patients with relapsing-remitting multiple sclerosis. The primary endpoint description states that MRI measures were assessed in 100 patients.
Intervention
BCD-033, an interferon beta 1a drug, given by subcutaneous injection at 44 µg three times per week. The BCD-033 arm description specifies treatment for 92 weeks.
Comparator
The active comparator was Rebif, also interferon beta 1a, and the trial also included a placebo group. The Rebif arm description specifies Rebif for 48 weeks followed by open-label BCD-033. The placebo arm description specifies placebo for 48 weeks followed by open-label BCD-033.
Primary question
After 52 weeks of full-dose interferon beta 1a, how did the number of combined unique active MRI lesions compare between BCD-033 and Rebif? The registry describes the study hypothesis as equivalence of efficacy and safety between the investigational drug and Rebif. The registry record does not report an equivalence margin or a direct inferential result for the primary endpoint, so the descriptive endpoint summaries alone cannot establish equivalence.
The study also included a placebo arm and listed relapse and MRI outcomes among its secondary outcomes. Those outcomes provide additional context about the trial’s measures, but the primary question concerns the MRI lesion count and the two active treatments. The trial record identifies the study as randomized and parallel-group, with quadruple masking. The official title describes it as double-blinded. Its registry status is completed.
3. Trial Design
This was a randomized, parallel-group study with three groups: BCD-033, Rebif and placebo. The registry lists the phase as Phase 2 and Phase 3 and the status as completed. The sponsor was Biocad. The brief summary describes a double-blind, placebo-controlled design with an active comparator; the masking field records quadruple masking, while the official title describes the study as double-blinded.
The BCD-033 arm received subcutaneous BCD-033 at 44 µg (0,5 ml) three times per week, every other day, for 92 weeks. The Rebif arm received 44 µg (0,5 ml) on the same weekly schedule for 48 weeks, followed by 48 weeks of open-label BCD-033. The placebo arm received 0,5 ml on the same schedule for 48 weeks, followed by 72 weeks of open-label BCD-033. These are the treatment sequences as described in the registry; further details about how the sequences were implemented are not reported in the registry record.
The primary endpoint was assessed after 52 weeks of full-dose interferon beta 1a. The endpoint description identifies BCD-033 and Rebif as the active treatments in that assessment. The stated primary endpoint population for MRI analysis was 100 patients, while the arm-level summaries list 44 for BCD-033 and 46 for Rebif. The registry does not explain the relationship between these population descriptions.
The study record gives enrollment as 163 and describes the total duration of therapy as about 2 years. It lists a start date of 2015-02-12 and primary completion on 2016-11-21. No additional details about allocation procedures, masking implementation, withdrawals or follow-up completeness are 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 | BCD-033 | Rebif/BCD-033 | Placebo/BCD-033 |
|---|---|---|---|
| STARTED | 53 | 56 | 54 |
| Recived One Injection of Drug | 53 | 55 | 54 |
| COMPLETED | 40 | 43 | 43 |
| NOT COMPLETED | 13 | 13 | 11 |
Analysis population for the primary outcome, as defined in the registry: The primary endpoint was assessed after 52 weeks of use of IFN-β1a (BCD-033 and Rebif) in a full dose (44 μg). In the analysis of the effeciency of MRI indicators included 100 patients
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 | BCD-033 | Rebif / BCD-033 | Placebo / BCD-033 | Total |
|---|---|---|---|---|---|
| Participants analysed | 53 | 55 | 54 | 162 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 53 | 55 | 54 | 162 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 28.00 (25.00 to 39.0) | 30.00 (26.0 to 37.0) | 29.5 (26.0 to 38.0) | 29.0 (26.0 to 38.0) |
| Sex: Female, Male: Female | Participants | 38 | 31 | 34 | 103 |
| Sex: Female, Male: Male | Participants | 15 | 24 | 20 | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Combined Unique Active Lesions, measured over 52 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | lesions |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of combined unique active lesions, or CUA lesions, on MRI after 52 weeks of full-dose interferon beta 1a. It counts new lesions with contrast uptake on T1 images and new or expanding lesions on T2 images. A lesion visible on both T1 and T2 images is counted once rather than twice. The endpoint therefore represents MRI evidence of new or changing lesion activity during the specified assessment period.
The registry reports the endpoint as a median with an inter-quartile range. The BCD-033 median was 0 lesions, with an inter-quartile range from 0.0 to 1.25. The Rebif median was 0 lesions, with an inter-quartile range from 0.0 to 1.0. These summaries describe the middle of each group’s distribution and its central spread; they do not show how every participant’s result was distributed.
Counting unique lesions avoids counting the same lesion twice when it appears on both MRI sequences. MRI lesion measures can provide a structured way to assess disease activity in a trial. However, the registry record does not report a direct between-group estimate, confidence interval, p-value, or equivalence analysis for this primary endpoint. The two medians and their inter-quartile ranges are descriptive summaries, not by themselves a test of equivalence or a complete account of the difference between treatment groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry’s primary endpoint summaries are descriptive. Both active-treatment groups had a median of 0 combined unique active lesions after 52 weeks. The inter-quartile range was 0.0 to 1.25 for BCD-033 and 0.0 to 1.0 for Rebif. These summaries indicate that the middle observation in each group was at the reported lower bound, while the central spread extended above zero. They do not establish that all participants had zero lesions, nor do they describe the full distribution of individual outcomes.
No direct inferential comparison for the primary endpoint is reported in the registry record. In particular, no confidence interval for the between-group difference, p-value, or equivalence margin is posted for the CUA outcome. The stated study hypothesis was equivalence, but a pair of similar medians cannot on its own demonstrate equivalence. Such a conclusion requires a defined margin and an analysis that evaluates the uncertainty around the treatment difference against that margin; those details are not reported in the registry record.
The secondary annual relapse rate summaries give means of 0.113 for BCD-033, 0.091 for Rebif / BCD-033, and 0.109 for Placebo / BCD-033. The registry does not list sponsor-reported analyses for these outcomes. The displayed pairwise estimates are unadjusted recalculations from the posted summary statistics. For BCD-033 compared with Placebo / BCD-033, the mean difference is 0.004, with a 95% confidence interval from -0.136 to 0.144 and p = 0.955. For Rebif / BCD-033 compared with Placebo / BCD-033, the mean difference is -0.018, with a 95% confidence interval from -0.152 to 0.116 and p = 0.792. Both intervals include zero, so these recalculations do not provide clear evidence of a difference in either direction. They are not the registry’s reported analyses and should not be treated as the trial’s formal conclusions.
The record does not report an inferential primary endpoint result, the prespecified statistical analysis plan, or methods for handling multiple outcomes. That limits how confidently the posted summaries can be interpreted as a coordinated test of the study hypothesis. The planning illustrations based on the observed relapse-rate effects are not measures of the trial’s achieved power. They show hypothetical sample-size needs under stated assumptions, not what the trial was designed to detect or what it could reliably rule out.
9. Statistical Methods Explained
Statistical interpretation depends on distinguishing the posted descriptive summaries from the unadjusted recalculations. The registry reports medians and inter-quartile ranges for the primary MRI endpoint, and means and standard deviations for the annual relapse rate. The recalculated relapse-rate comparisons use those arm-level summaries. The registry does not list sponsor-reported analyses for the secondary outcomes, and no primary-endpoint comparison is posted.
What does a median and inter-quartile range describe?
In general, a median is the middle value in an ordered set of observations. The inter-quartile range describes the span from the lower to the upper quartile, covering the central half of the observations. These summaries are often useful when a measure is skewed or includes many low values. In this trial, the reported median CUA count is 0 in both active-treatment groups; the reported inter-quartile ranges extend from 0.0 to 1.25 for BCD-033 and from 0.0 to 1.0 for Rebif. Those statistics do not reveal the complete distribution, the frequency of every possible count, or the extent of any difference outside the central part of the distributions.
A descriptive comparison of medians is not equivalent to a test of equivalence. In general, equivalence testing requires a prespecified range of differences that would count as sufficiently similar, and an inferential procedure that assesses whether uncertainty is contained within that range. The registry record does not report an equivalence margin or an inferential analysis for the primary CUA endpoint. The stated equivalence hypothesis therefore cannot be evaluated from the posted primary summaries alone.
How should the relapse-rate comparisons be read?
The annual relapse rate is reported as a mean with a standard deviation for each arm. A mean describes the arithmetic average, while the standard deviation describes the spread of observations around that average. The posted mean differences compare the active-treatment summaries with the Placebo / BCD-033 summary. These are unadjusted recalculations from summary statistics, not sponsor-reported analyses. The comparison estimates are 0.004 for BCD-033 and -0.018 for Rebif / BCD-033. Their confidence intervals include zero, and the associated unadjusted p-values are 0.955 and 0.792.
In general, a confidence interval gives a range of values compatible with the data under the method used to calculate it. A wide interval indicates substantial uncertainty about the size and direction of the difference. When an interval includes zero for a difference, the data do not distinguish that estimate from no difference at the confidence level used. This does not prove that the true difference is zero. It also does not establish equivalence, especially when no equivalence margin is available.
A p-value describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. The p-values are unadjusted recalculations. They do not account for the possibility of examining several outcomes or comparisons, and the registry does not report whether or how the trial’s own analyses addressed multiplicity.
What do the planning illustrations mean?
The sample-size planning illustrations use the observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. They consider detecting stated fractions of the observed effect. In general, an observed effect is uncertain, and planning from it can be unstable: a small observed difference can imply very large hypothetical sample sizes, while a different underlying effect would lead to different requirements. The calculations are illustrations under their stated assumptions, not evidence that the trial had a particular power, and not a record of the trial’s original sample-size justification. That justification is not reported in the registry record.
Over-dispersion is a general concern for count outcomes when variability exceeds what a simple count model expects. It can affect standard errors and the reliability of model-based confidence intervals or tests if the model does not account for it. The CUA endpoint is a lesion count, but the registry does not report the primary endpoint’s inferential model or dispersion assessment. The annual relapse rate is also a count-based measure, but its posted arm summaries alone do not disclose what model the sponsor used or whether over-dispersion was assessed. No modeling choice should be inferred from the recalculated comparisons.
What cannot be established from the posted analysis details?
The registry lists 17 outcome measures and 0 analyses. It reports seven secondary outcomes, including annual relapse rate, proportion without confirmed relapse, relapse-free time and combined unique active lesions. The listed secondary outcomes include repeated titles, but the record does not provide a complete analysis plan that clarifies every outcome’s role or the hierarchy among comparisons. Details of endpoint-specific populations, covariate adjustment, missing-data methods, censoring, model diagnostics and multiplicity control are not reported in the registry record. Those omissions matter because statistical conclusions depend not only on observed summaries but also on the analysis population, assumptions and prespecified decision rules.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 17 outcome measures and reports seven secondary outcomes, including relapse and MRI measures. The secondary outcome list repeats some titles. It does not provide a complete hierarchy of outcomes, explain whether repeated entries represent different assessment periods or analysis definitions, or identify which secondary comparisons were designated as confirmatory. The record lists 0 analyses. A statistical analysis plan is not reported in the registry record.
Multiplicity matters when several outcomes or comparisons are tested. In general, the more tests considered, the greater the possibility that at least one will appear statistically notable by chance if results are interpreted without accounting for the full set. Methods such as adjustment or a prespecified testing order can address this issue, but whether these methods were used is not reported in the registry record. The unadjusted p-values for the recalculated annual relapse rate comparisons should therefore be read as unadjusted results, not as multiplicity-controlled evidence.
Missing-data procedures are not reported in the registry record. It does not describe how missing MRI assessments, relapse observations or follow-up information were handled, whether participants were excluded from particular analyses, or what assumptions were used for any missing values. The record also does not describe an analysis population such as intention-to-treat or per-protocol for the primary comparison. The endpoint description says MRI analysis included 100 patients, while the primary arm summaries list 44 for BCD-033 and 46 for Rebif; the registry does not explain this relationship.
These reporting gaps do not demonstrate that the trial lacked such methods. They mean that the registry record does not allow readers to assess them. Without the analysis population, missing-data approach, multiplicity strategy and primary inferential result, the strength and scope of any formal conclusion about the trial’s hypothesis remain uncertain.
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 |
|---|---|---|---|
| BCD-033 | 0 | 53 | 0.0% |
| Rebif | 0 | 55 | 0.0% |
| Placebo/BCD-033 | 2 | 54 | 3.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BCD-033 | 0 of 53 |
| Rebif | 0 of 55 |
| Placebo/BCD-033 | 0 of 54 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BCD-033 | 35 of 53 |
| Rebif | 32 of 55 |
| Placebo/BCD-033 | 34 of 54 |
Most frequent serious adverse event terms
| Event term | Organ system | BCD-033 | Rebif | Placebo/BCD-033 |
|---|---|---|---|---|
| nephrotic syndrome | Renal and urinary disorders | 0 of 53 | 0 of 55 | 1 of 54 |
| Left hemophthalmos | Eye disorders | n/a of 53 | n/a of 55 | 1 of 54 |
| Chronic viral hepatitis B | Infections and infestations | n/a of 53 | n/a of 55 | 1 of 54 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BCD-033 | Rebif | Placebo/BCD-033 |
|---|---|---|---|---|
| flu-like syndrom | General disorders | 15 of 53 | 16 of 55 | 19 of 54 |
| local reaction | General disorders | 15 of 53 | 12 of 55 | 10 of 54 |
| neutropenia | Investigations | 11 of 53 | 4 of 55 | 10 of 54 |
| fever | General disorders | 7 of 53 | 6 of 55 | 6 of 54 |
| lymphopenia | Investigations | 5 of 53 | 4 of 55 | 4 of 54 |
| thrombocytopenia | Investigations | 3 of 53 | 5 of 55 | 3 of 54 |
| increased ALT | Investigations | 3 of 53 | 4 of 55 | 3 of 54 |
| headache | General disorders | 3 of 53 | 3 of 55 | 3 of 54 |
Serious events with the highest arm-level rate: nephrotic syndrome (1.9%), left hemophthalmos (1.9%), chronic viral hepatitis b (1.9%).
The registry reports serious adverse events for the BCD-033, Rebif and Placebo/BCD-033 groups. The numbers at risk for serious adverse events were 53, 55 and 54, respectively. Serious adverse events were reported for 0 in the BCD-033 group, 0 in the Rebif group and 2 in the Placebo/BCD-033 group. Deaths were reported as 0 in each group. These are counts as posted; they should not be converted into comparative rates without further analysis.
Other adverse events were reported for 35 of 53 in the BCD-033 group, 32 of 55 in the Rebif group and 34 of 54 in the Placebo/BCD-033 group. These counts describe the registry’s adverse-event reporting, not the severity, duration or causal relationship of every event. The record lists nephrotic syndrome, Left hemophthalmos and Chronic viral hepatitis B among the top serious adverse event terms, each at 1.9%. It does not specify in this summary which group or groups each listed term occurred in.
Group exposure periods differ in the registry’s treatment descriptions, including transitions to open-label BCD-033. The safety counts alone do not account for exposure time or provide adjusted comparisons. Further details on event definitions, collection periods, relatedness assessments and statistical comparisons are not reported in the registry record. These summaries describe reported events and should not be treated as a complete comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The posted primary endpoint results show that the median combined unique active lesion count was 0 in both BCD-033 and Rebif groups at 52 weeks, with the reported inter-quartile ranges extending above zero. This is a descriptive summary of MRI lesion activity in the analyzed groups. It does not say that every participant had no new or expanding lesions, and it does not quantify the full difference between treatments.
The registry’s stated hypothesis was equivalence of efficacy and safety between BCD-033 and Rebif. The primary endpoint summaries do not establish equivalence because the registry record does not report an equivalence margin, direct treatment-effect estimate or inferential result for that endpoint. Similar medians are not enough to show that any difference lies within a clinically acceptable range. Equivalence also cannot be inferred from a non-significant test, and no such primary test is posted.
The unadjusted recalculated annual relapse-rate comparisons do not show clear evidence of a difference: their confidence intervals include zero. These recalculations are based on posted summary statistics and are not listed as sponsor-reported analyses. They do not prove that the groups are identical, demonstrate equivalence, or answer the primary MRI question. The registry does not report multiplicity methods, missing-data procedures or a complete analysis population for these outcomes.
The safety record reports serious adverse events in the groups, including 2 in the Placebo/BCD-033 group and 0 in each active-treatment group, as well as other adverse-event counts and listed serious-event terms. Those figures are descriptive and do not account for differences in exposure periods or provide a formal adjusted comparison.
Overall, the registry supports a limited reading of the posted summaries, not a definitive judgment about efficacy or safety. It does not report enough of the primary analysis and statistical methods to determine whether the study’s stated equivalence hypothesis was met. The results described should not be extended beyond the outcomes, groups and assessment periods recorded.
13. Why This Trial Matters Statistically
This trial is statistically notable because its stated objective was equivalence, while the registry’s primary endpoint results are descriptive medians and inter-quartile ranges. Equivalence questions require more than observing similar central summaries: they depend on a prespecified margin and an analysis that quantifies uncertainty in the between-group difference. Neither the margin nor a primary inferential result is reported in the registry record. That distinction illustrates why a study’s stated hypothesis and the statistics available for evaluating it must be considered together.
The endpoint also illustrates how summaries can conceal important distributional features. Both groups have a median of 0 lesions, yet their inter-quartile ranges extend above zero. A median alone does not describe the entire spread or show whether groups differ in the upper part of their distributions. The registry reports no direct primary comparison to clarify that uncertainty.
For the secondary annual relapse rate, the registry posts arm-level means and standard deviations, while the pairwise estimates are unadjusted recalculations. Their confidence intervals include zero, and the registry does not identify them as sponsor-reported analyses. This distinction matters: a recalculation from summary statistics can be useful for orientation, but it is not a substitute for a trial’s prespecified analysis, especially when outcome multiplicity and analysis populations are not documented.
The planning illustrations also demonstrate why sample-size figures must be separated from trial results. They are based on the observed effects under stated assumptions and are not evidence of observed power or the original design justification. The record does not report that justification. More broadly, the missing analysis details limit independent evaluation of the stated hypothesis. The trial’s statistical importance lies not in a definitive conclusion from the posted numbers, but in the need to distinguish descriptive summaries, unadjusted recalculations and formal evidence for equivalence.
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 registry record does not post a direct inferential comparison for the primary CUA endpoint. It gives group medians and inter-quartile ranges but no treatment-effect estimate, confidence interval, p-value or equivalence margin. As a result, the primary summaries cannot show whether the estimated difference meets any prespecified equivalence criterion. The relationship between the stated MRI analysis population of 100 patients and the arm-level primary summaries is also not explained.
For the secondary annual relapse rate, the arm means and standard deviations are available, but the comparison estimates are unadjusted recalculations rather than sponsor-reported analyses. The record does not provide a complete statistical analysis plan, model specification, multiplicity strategy or rationale for the chosen analysis. The listed outcome set includes repeated titles, and the registry lists 0 analyses. These features make it difficult to determine which secondary results were intended to be confirmatory or how they relate to the stated primary hypothesis.
Missing-data methods, analysis populations and endpoint-specific denominators are not reported in the registry record. The record does not explain whether observations were excluded, how incomplete follow-up was treated, or whether any assumptions were made about missing outcomes. The trial’s sample-size justification and any interim analyses are also not reported in the registry record. The posted sample-size planning illustrations use observed effects and stated assumptions; they should not be taken as the trial’s original design calculations.
The treatment descriptions include different durations and transitions to open-label BCD-033. The registry safety counts do not provide exposure-adjusted comparisons or details sufficient to assess how events were collected across those periods. The safety record also does not link each listed serious-event term to a group in its summary. These limitations restrict interpretation of both the comparative outcome findings and the safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Efficacy and Safety of Drugs BCD-033 and Rebif for Treatment of Patients With Multiple Sclerosis — NCT02727907.
- Registry record last updated 2023-02-17; status last verified 2022-05.
- Results first posted 2023-02-17.
- 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 describes a completed randomized, parallel-group Phase 2 and Phase 3 study of BCD-033, Rebif and placebo in multiple sclerosis. Its official title specifies relapsing-remitting multiple sclerosis; the record lists quadruple masking and describes a double-blinded design. The study’s stated hypothesis was equivalence of efficacy and safety between BCD-033 and Rebif.
The primary endpoint was the number of combined unique active MRI lesions at 52 weeks. The median was 0 lesions in each active-treatment group, with inter-quartile ranges of 0.0 to 1.25 for BCD-033 and 0.0 to 1.0 for Rebif. No primary inferential comparison or equivalence margin is reported in the registry record. Secondary relapse-rate comparisons are unadjusted recalculations from posted summary statistics; their confidence intervals include zero. The record also reports group-level adverse-event counts, but not exposure-adjusted safety comparisons.
Missing-data methods, multiplicity procedures, analysis populations and the trial’s original sample-size justification are not reported in the registry record. The posted results therefore support descriptive interpretation, but do not establish whether the stated equivalence hypothesis was met.