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 Multicenter, Open-label, RebiSmart™ Autoinjector Ease of Use Study (NCT01036165), a na phase 3 study. The primary outcome is The Primary Endpoint is the Proportion of RMS Subjects Rating the RebiSmart™ Autoinjector as 'Easy to Use' or 'Very Easy to Use' for Self-injection in a User Trial Questionnaire..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01036165 |
| Phase | Phase 3 |
| Condition | Multiple Sclerosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 103 |
| Arms in the primary outcome | n/a |
| Lead sponsor | EMD Serono |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with relapsing multiple sclerosis (RMS) treated with Rebif® 44 mcg subcutaneously three times a week. The registry record reports enrollment of 103 participants. It does not provide further eligibility details or describe the characteristics of the participants in the posted results.
Intervention
The device under evaluation was the RebiSmart™ electronic autoinjector. The study assessed its use for self-injection of Rebif®; the official title identifies the treatment as Rebif® 44 mcg administered subcutaneously three times a week. The intervention listed in the record is the device.
Comparator
There was no separate comparator group. The registry identifies the study as single-group, with allocation listed as not applicable. Consequently, the study does not provide a randomized or concurrent comparison between RebiSmart™ and another injection device or method.
Primary question
At 12 weeks, what proportion of RMS subjects rated the RebiSmart™ autoinjector “Easy to Use” or “Very Easy to Use” for self-injection? The endpoint was based on responses to a user trial questionnaire. The numerical proportion and its 95% confidence interval are not reported in the registry record, so the size and precision of the observed response cannot be assessed from the posted results.
The study also set out to assess acceptability, satisfaction, and reliable device function. These aims concern users’ experiences and device use in the study setting. They are different from a comparison of treatment effects: with no control group, the design cannot establish whether ratings would differ under another device or injection approach.
3. Trial Design
The registry record describes a completed, open-label, single-group, multicenter study of the RebiSmart™ electronic autoinjector. The official title calls it a twelve-week, Phase IIIb trial; the registry phase field lists Phase 3. Enrollment was 103. The record lists EMD Serono as sponsor, a start date of 2010-01, and primary completion in 2010-08.
Participants with relapsing multiple sclerosis were treated with Rebif® 44 mcg subcutaneously three times a week, with the device evaluated for self-injection. Because the study was open-label, participants and study personnel were not masked to the device being used. Masking is listed as none. The record identifies no allocation to multiple study groups, and the allocation field is not applicable.
The primary endpoint was measured at 12 weeks using User Trial Questionnaire-B, Question 13, which asked for an overall rating of the experience of using the injection device. The primary outcome was the proportion rating use as “Easy to Use” or “Very Easy to Use.” The registry also describes multiple secondary endpoints based on questions about RebiSmart™ use-related outcomes.
This design can describe questionnaire responses among participants using the device during the study. It does not provide a randomized comparison, and it cannot separate device-related impressions from other influences on participants’ responses. Further details about the planned analysis, participant flow beyond the adverse-event entries, and study procedures 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.
Before assignment: Subjects who signed informed consent and satisfied the eligibility critera at screening returned to the clinic on study day 1 to begin treatment with the Rebismart autoinjector. All subjects participating in the trial received Rebif 44 mcg sc tiw using the Rebismart autoinjector for 12 weeks.
Overall Study
| Stage | Subject Disposition |
|---|---|
| STARTED | 103 |
| COMPLETED | 88 |
| NOT COMPLETED | 15 |
Reasons for not completing this period:
| Reason | Subject Disposition |
|---|---|
| Adverse Event | 6 |
| Lost to Follow-up | 2 |
| Withdrawal by Subject | 3 |
| Device Related Issues | 3 |
| Problems finding proper area to inject | 1 |
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 | Subject Disposition |
|---|---|---|
| Participants analysed | 103 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 103 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age Continuous | years | 46.4 (SD 9.35) |
| Sex: Female, Male: Female | Participants | 82 |
| Sex: Female, Male: Male | Participants | 21 |
| Region of Enrollment: United States | participants | 103 |
6. Primary Endpoint
The registry lists the primary outcome as The Primary Endpoint is the Proportion of RMS Subjects Rating the RebiSmart™ Autoinjector as 'Easy to Use' or 'Very Easy to Use' for Self-injection in a User Trial Questionnaire., measured over at 12 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Proportion of subjects |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the proportion of RMS subjects who rated the RebiSmart™ autoinjector “Easy to Use” or “Very Easy to Use” for self-injection at 12 weeks. It comes from User Trial Questionnaire-B, Question 13, which asks for an overall rating of the participant’s experience using the injection device. The registry says that the reported mean and confidence interval refer to the proportion responding positively.
A proportion translates individual questionnaire responses into the share of participants meeting a defined response criterion. This gives a concise description of how often participants selected one of the two positive ratings. The criterion makes the endpoint interpretable as a favorable-response rate, rather than as a comparison of average scores across all possible response categories.
Such a measure is useful for a device-usability question because the study seeks participants’ overall assessments of using the device for self-injection. It remains a subjective, questionnaire-based outcome. The result would describe responses in this open-label study; it would not by itself establish comparative usability against another device, nor would it establish an effect on the course of multiple sclerosis.
The registry specifies worst-case replacement for missing values in this endpoint. However, the primary proportion and its 95% confidence interval are not reported in the registry record. Without those values, the observed response rate and the precision of its estimate cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry record describes the endpoint and its measurement but does not report the primary endpoint estimate. It states that the outcome is the proportion of participants rating the device “Easy to Use” or “Very Easy to Use” at 12 weeks, and that the estimate is accompanied by a 95% confidence interval. Neither the proportion nor the interval is reported in the registry record. As a result, the magnitude of the recorded response and the uncertainty around it cannot be evaluated from the posted results.
The study enrolled 103 participants, but enrollment alone does not indicate how many contributed usable responses to the primary endpoint. The record says missing values were replaced with a worst-case response, but it does not report the number of missing responses, the resulting analysis denominator, or participant-level disposition for the primary endpoint. It is therefore not possible to reconstruct the endpoint estimate from the registry record.
General statistical interpretation: a confidence interval describes uncertainty in an estimated quantity under the assumptions of the analysis. It does not mean that the individual participant responses are uncertain; rather, it conveys how precisely the study estimates the underlying response proportion. The intended interval level is 95%, but without its limits, no conclusion about precision is possible.
The design is single-group and open-label. Responses can describe the experience reported by participants using RebiSmart™ in the study, but there is no concurrent comparison group to show how ratings might have differed with another device or approach. Open-label knowledge of the device may also be relevant when interpreting subjective ratings. These design features do not invalidate the descriptive endpoint, but they constrain the kinds of conclusions it can support.
The study’s stated aims included ease of use, acceptability, satisfaction, and reliability of correct function for self-injection. The registry lists secondary outcomes based on questionnaire questions, but does not give their numerical results or a detailed analysis plan. The posted adverse-event entries are separate from the primary usability endpoint and cannot substitute for its missing estimate.
No recalculated primary effect is available from the posted summary information. There is no reported comparison effect to interpret and no basis for estimating how a result would differ from a control condition. The appropriate reading is therefore limited: the study was designed to collect a 12-week user rating, but the registry record does not provide the numerical result needed to describe the observed rate or its precision.
9. Statistical Methods Explained
The registry describes a single-group study and a primary outcome expressed as a proportion. The interpretation of that outcome differs from the interpretation of a treatment-versus-control effect. The endpoint summarizes the fraction of participants meeting the favorable questionnaire-response definition; it is not a difference between groups.
What does the proportion represent?
The primary response criterion combines ratings of “Easy to Use” and “Very Easy to Use.” Each participant’s answer is classified according to whether it meets that criterion, and the endpoint is the proportion responding positively. General explanation: a proportion is a summary of a binary classification, even when the original questionnaire offers more than two response options. The registry identifies the response categories used for the positive classification, but does not report the final numerical proportion.
The record labels the outcome as a mean and says the mean and confidence interval refer to the proportion of subjects responding positively. This is a way of reporting a proportion as an average of response indicators. The reported unit is “Proportion of subjects.” The numerical estimate itself is not reported in the registry record.
How should a confidence interval be understood?
The registry specifies a 95% confidence interval for the primary endpoint. General explanation: an interval gives a range of values compatible with the observed data under the statistical method and its assumptions, and communicates the precision of the estimate. A narrower interval indicates greater precision than a wider interval, all else being equal. No interval limits are reported in the registry record, so its width and the precision of the estimate cannot be assessed.
A confidence interval is not a guarantee that a particular range contains the true value, nor does it describe variation in an individual participant’s rating. It relates to uncertainty in the estimated response proportion. The record does not identify the specific confidence-interval calculation method, so the method’s detailed assumptions cannot be checked.
What does the missing-value rule imply?
The primary endpoint description states that missing values were replaced with a worst-case response. General explanation: a conservative missing-data rule assigns missing observations an outcome considered unfavorable for the endpoint, rather than omitting them as if their absence were unrelated to their responses. This may affect the estimated proportion, but its effect cannot be quantified without knowing how many values were missing and how the analysis applied the rule.
The record does not report the missing-response count, the number analyzed for the primary outcome, or sensitivity analyses using alternative assumptions. It also does not explain how missing values were handled for secondary questionnaire endpoints. The phrase “worst case” is present, but further operational detail is not reported in the registry record.
Why does the single-group design matter?
General explanation: a single-group study can describe outcomes observed among participants receiving or using the study intervention. It does not estimate a randomized between-group contrast. Here, the record lists one study group and no comparator. A favorable user rating, if reported, would describe responses in that group; without a concurrent control, it cannot establish how ratings would compare with another device or method.
The study was open-label, with masking listed as none. Because the endpoint is a subjective rating, participants’ awareness of the device is relevant to interpretation. This is a design consideration, not evidence that responses were biased in a particular direction. The registry does not report methods intended to assess or adjust for such influences.
What can be inferred about analysis planning?
The registry includes a general planning-illustration specification based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Those assumptions describe a planning illustration, not the reported design of this single-group study. No numerical planning results or observed primary effect are reported in the registry record, and the study’s own sample-size justification is not reported in the registry record.
General explanation: a sample-size planning exercise asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen operating characteristic. Such a calculation depends on the effect size and other inputs. It is not an observed result, and it does not show the probability that a completed study’s finding is correct. The registry record does not provide enough numerical information to discuss a specific planning estimate.
The registry reports one analysis and two outcome measures, but does not give detailed statistical methods for the primary or secondary outcomes. It does not report the confidence-interval construction method, a significance test for the primary endpoint, or an analysis population definition. Therefore, a fuller assessment of analytic choices and robustness is not possible from the posted results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and describes multiple secondary endpoints based on questions from the user trial questionnaire. It reports two outcome measures and one analysis, but does not provide a detailed statistical analysis plan or explain how the secondary questions were analyzed. In particular, adjustment for multiple comparisons is not reported in the registry record.
Multiplicity matters when several outcomes or analyses are examined. General explanation: testing many questions can increase the chance of finding an apparently notable result by chance if each is interpreted independently. Prespecified priorities and an adjustment strategy can help clarify how to interpret multiple statistical tests. The registry identifies the primary question, but does not report whether secondary endpoints were tested formally, whether any multiplicity adjustment was used, or how secondary results were prioritized.
The primary endpoint description states that missing values were replaced with a worst-case response. The registry does not report the number of missing responses, the number included in the primary analysis, or the precise implementation of this rule. It also does not report sensitivity analyses showing whether conclusions change under alternative missing-data assumptions.
The analysis population is not described in the registry record. It is therefore unclear from the posted results which enrolled participants were included in each endpoint analysis, or whether any participants were excluded from the primary analysis. Enrollment of 103 should not be treated as the primary endpoint denominator without a reported analysis denominator.
These gaps limit assessment of both the reliability of the endpoint estimate and the interpretation of secondary questionnaire findings. The primary numerical result and its confidence interval are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Subject Disposition | 1 | 99 | 1.0% |
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 |
|---|---|
| Subject Disposition | 92 of 103 |
Most frequent serious adverse event terms
| Event term | Organ system | Subject Disposition |
|---|---|---|
| Appendicitis | Infections and infestations | 1 of 99 |
| Nephrolithiasis | Renal and urinary disorders | 1 of 99 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Subject Disposition |
|---|---|---|
| Injection Site Pain | General disorders | 52 of 103 |
| Injection site erythema | General disorders | 35 of 103 |
| Injection site haematoma | General disorders | 12 of 103 |
| Influenza like illness | General disorders | 11 of 103 |
| Multiple Sclerosis relapse | Nervous system disorders | 9 of 103 |
| Urinary Tract Infection | General disorders | 8 of 103 |
| Injection site haemorrhage | General disorders | 7 of 103 |
| Headache | Nervous system disorders | 6 of 103 |
Serious events with the highest arm-level rate: appendicitis (1.0%), nephrolithiasis (1.0%).
The registry’s subject-disposition entry lists 99 participants at risk in the serious adverse-event category and 1 affected. For other adverse events, it lists 103 at risk and 92 affected. These are the figures recorded in the adverse-event entry; the registry does not explain the different at-risk denominators or provide further participant-flow detail alongside them.
The serious-event terms listed are appendicitis and nephrolithiasis, each recorded as 1.0%. The record does not provide additional context about the timing, clinical course, or relationship of these events to the device or treatment. The listed terms should therefore be read as reported event categories, not as evidence of causation.
Deaths are not reported in the registry record. A missing death value should not be interpreted as a reported count of zero. The adverse-event figures also do not describe the primary questionnaire outcome, and they cannot establish comparative safety because the study has no separate control group.
General explanation: adverse-event counts are most informative when their denominators, observation periods, event definitions, and analysis populations are clear. The registry provides some counts and percentages, but further details are not reported in the registry record. These figures describe the entries in this study and do not, by themselves, establish whether an event was caused by the device or treatment.
12. What the Result Does, and Does Not, Mean
The study addresses a specific descriptive question: how participants rated their experience using the RebiSmart™ electronic autoinjector for self-injection of Rebif® at 12 weeks. The registry describes the favorable response categories and the questionnaire item used to elicit the rating. It also states that missing primary endpoint values were replaced with a worst-case response.
However, the primary proportion and its 95% confidence interval are not reported in the registry record. Without those values, the posted information does not establish what proportion gave a favorable rating or how precisely that proportion was estimated. Enrollment of 103 does not fill this gap because the number contributing to the primary endpoint is not reported.
Even if a numerical response rate were available, its interpretation would remain descriptive. This was an open-label, single-group study with no comparator. The study can characterize the reported experience of participants using the device in this setting, but cannot show how those experiences compare with another device or injection method. The subjective nature of the questionnaire and the absence of masking are relevant considerations; they do not establish that responses were biased.
The stated study aims also include acceptability, satisfaction, and reliable correct function. Numerical results for those outcomes are not reported in the registry record. The listed adverse-event entries are a separate type of information and do not answer the primary usability question.
Accordingly, the registry description supports understanding of the intended endpoint and design, but not a numerical conclusion about the observed usability response. It does not establish a comparative effect, and it does not establish a treatment effect on multiple sclerosis. The interpretation should stay within the study’s questionnaire-based, single-group scope.
13. Why This Trial Matters Statistically
This study is statistically notable because it illustrates a common distinction between a clearly defined endpoint and a result that can be interpreted quantitatively. The registry specifies a concrete response criterion, a questionnaire item, a 12-week assessment time, and a confidence interval level. Yet the numerical primary estimate and interval are not reported in the registry record. Without them, readers cannot judge the observed response rate or its precision.
The design also illustrates how the research question shapes the analysis. A single-group usability study can describe the ratings of participants using a device. It is not designed as a randomized comparison of devices, and it cannot estimate a between-group difference. That distinction matters when interpreting subjective outcomes: a response proportion is a description of this study group, not proof of comparative advantage.
The handling of missing questionnaire responses is another important statistical detail. The registry says missing primary values were replaced with a worst-case response. That rule makes the missing-data assumption visible, but the record does not give the missing count or analysis denominator. Without those details, readers cannot assess how much the rule might influence the estimate.
Finally, the registry’s stated planning illustration uses assumptions for a two-arm calculation, while the trial itself is described as single-group. The record does not report the study’s own sample-size justification or numerical planning outputs. Keeping a planning illustration distinct from the actual design and observed analysis is essential: planning assumptions are not results, and a sample-size calculation is not evidence of the endpoint’s observed precision.
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 primary limitation for statistical interpretation is the absence of the primary endpoint estimate and its 95% confidence interval from the registry record. Consequently, the central usability result cannot be described numerically. The record also does not report the primary endpoint denominator or the number of missing questionnaire responses.
The single-group, open-label design limits comparative interpretation. There is no control group and no masked assessment reported. The primary endpoint is a subjective overall rating, so participants’ awareness of the device is relevant context, although the registry does not establish that it affected responses.
The record does not describe participant characteristics, detailed eligibility criteria, or the analysis population. It does not provide the specific confidence-interval method, a detailed plan for secondary outcomes, or whether multiplicity was addressed. The description of worst-case replacement for missing primary responses does not include implementation details or sensitivity analyses.
The registry lists adverse-event counts and terms but does not provide further information about timing, causality assessment, or the explanation for the different at-risk counts. Deaths are not reported in the registry record. These limits prevent a fuller assessment of the adverse-event entries and their interpretation.
Finally, the stated planning illustration is based on a two-arm framework, whereas the study is described as single-group. Numerical planning outputs and the trial’s own sample-size justification are not reported in the registry record. The available description therefore supports understanding of the design and intended measures more than an appraisal of the study’s numerical findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Multicenter, Open-label, RebiSmart™ Autoinjector Ease of Use Study — NCT01036165.
- Registry record last updated 2013-08-08; status last verified 2013-08.
- Results first posted 2010-12-22.
- 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 a completed, open-label, single-group, multicenter study of the RebiSmart™ electronic autoinjector in subjects with relapsing multiple sclerosis treated with Rebif® 44 mcg subcutaneously three times a week. The official title describes a twelve-week Phase IIIb trial; the phase field lists Phase 3. Enrollment was 103. The record lists EMD Serono as sponsor, with a start date of 2010-01 and primary completion in 2010-08.
The primary endpoint was the proportion rating the device “Easy to Use” or “Very Easy to Use” at 12 weeks, based on a user trial questionnaire. Missing primary endpoint values were replaced with a worst-case response. The numerical primary result and 95% confidence interval are not reported in the registry record. The record also lists questionnaire-based secondary outcomes and adverse-event entries, but does not provide enough detail for a comparative analysis or a complete assessment of the analysis methods.