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 Non-interventional Study (NIS) in Patients With Restless Legs Syndrome in Daily Practise (NCT01113710), a registered phase not stated study. The primary outcome is Severity of Restless Legs Syndrome (RLS) at Bedtime.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01113710 |
| Phase | Phase not stated |
| Condition | Idiopathic Restless Legs Syndrome |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 687 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Pharma |
| Results posted | Yes |
2. Clinical Question
Population
People with idiopathic restless legs syndrome treated in routine practice. The registry record reports enrollment of 687 participants. The Full Analysis Set included 564 participants, and all 564 were included in the primary-outcome analysis.
Intervention
Neupro® (rotigotine), used as routine treatment in accordance with local marketing authorization for restless legs syndrome. The study was intended to describe effectiveness and safety under real-life conditions, including switching practice from other dopaminergic drugs and titration schemes.
Comparator
No randomized control group is described. The registry record does not state an allocation method or identify a like-for-like control arm. This is an observational study of treatment in practice, not a randomized comparison between Neupro® and another intervention.
Primary question
How did the recorded severity of restless legs syndrome at bedtime change from baseline to the end of the three-month observation period among participants included in the primary analysis? The registry record identifies the outcome measure but does not report the numerical mean change or its variability.
The primary endpoint uses Item 2 of the RLS-6 scale, an 11-point measure of symptom severity at bedtime. The scale runs from 0, described as “not present/completely satisfied,” to 10, described as “very severe/completely dissatisfied.” The study also listed satisfaction with sleep, daytime symptom severity at rest and during activity, and daytime tiredness as secondary outcomes.
This question is descriptive and concerns change during routine treatment. Because the study was non-interventional and no randomized comparison is reported, an observed change would not by itself separate treatment effects from other changes over time, patient selection, or the circumstances that led to treatment. The registry record does not report the primary result, so the size and precision of any change cannot be assessed from the posted information.
3. Trial Design
This was a completed, non-interventional observational study of Neupro® in patients with restless legs syndrome. Its stated purpose was to collect information about effectiveness and safety under real-life conditions consistent with local product information, and to describe switching from other dopaminergic drugs and treatment titration. Enrollment was 687. The study began in 2010-05, and primary completion was recorded in 2011-07.
Neupro® was recorded as the intervention, with routine treatment according to local marketing authorization. The registry record does not state a randomized allocation method or describe a comparator group suitable for a like-for-like treatment comparison. Accordingly, the design should be understood as observational rather than as a controlled trial that assigned participants to alternative treatments. The registry record does not report further details about treatment decisions or the frequency and timing of dose adjustments.
The primary outcome was change in bedtime restless legs syndrome severity from baseline to the end of the observation period, specified as three months. It was measured with Item 2 of the RLS-6 scale. The registry record reports that Last Observation Carried Forward (LOCF) was used for all outcomes. The Full Analysis Set comprised 564 participants, and 564 were included in the primary analysis. The record’s description of the Full Analysis Set refers to treatment exposure and valid baseline and post-baseline RLS-6 scores, although the available description is incomplete.
Six outcome measures and four secondary-outcome topics are recorded. These secondary topics are satisfaction with sleep, daytime RLS severity at rest, daytime RLS severity during activity, and daytime tiredness. The registry record lists zero analyses. It does not report numerical results for the primary endpoint or the secondary outcomes, so these measures identify what the study intended to assess rather than what magnitude of change was observed.
Safety information is recorded for 684 participants in the Neupro® group. The registry record reports serious and other adverse-event counts, as well as several serious-event terms with reported percentages. These safety observations arise in an observational setting and do not provide a randomized estimate of excess risk compared with an untreated or alternative-treatment group.
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: The Participant Flow contains single and multiple reasons for "Other" subject discontinuation. Therefore, individual "Other" reasons are listed below: Augmentation: 7 Problems with adhesiveness of patch: 6 Pruritus: 1 Tiredness: 1 Less effective than previous medication: 1 Application site reactions: 2 Neurotic: 1
Overall Study
| Stage | Neupro® |
|---|---|
| STARTED | 687 |
| COMPLETED | 418 |
| NOT COMPLETED | 269 |
Reasons for not completing this period:
| Reason | Neupro® |
|---|---|
| Adverse Event | 64 |
| Lack of Efficacy | 41 |
| No Information Available | 40 |
| Withdrawal by Subject | 28 |
| Lost to Follow-up | 20 |
| Lack of Efficacy/Withdrawal by Subject | 13 |
| Withdrawal by Subject/Adverse Event | 11 |
| Lack of Patient's Compliance | 8 |
| Other | 7 |
| Adverse Event/Other | 5 |
| Patient's Compliance/Lost to Follow up | 5 |
| Lack of Efficacy/Other | 4 |
Analysis population for the primary outcome, as defined in the registry: Of the 564 subjects in the Full Analysis Set (FAS), 564 are included in this analysis. The FAS consists of all patients receiving treatment with Rotigotine at least once \& for whom valid scores for item 2 \& item 3 of the RLS-6 scale at baseline \& at least one valid post baseline score for both item 2 \& item 3 of the RLS-6 scale is documented.
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 | Neupro® |
|---|---|---|
| Participants analysed | 687 | |
| Age Continuous | years | 65.6 (SD 12.6) |
| Age, Customized: <=18 years | Participants | 0 |
| Age, Customized: Between 18 and 65 years | Participants | 278 |
| Age, Customized: >=65 years | Participants | 408 |
| Age, Customized: Missing | Participants | 1 |
| Sex/Gender, Customized: Female | Participants | 494 |
| Sex/Gender, Customized: Male | Participants | 188 |
| Sex/Gender, Customized: Missing | Participants | 5 |
| Region of Enrollment: Germany | participants | 687 |
6. Primary Endpoint
The registry lists the primary outcome as Severity of Restless Legs Syndrome (RLS) at Bedtime, measured over From Baseline to end of Observation Period (3 months)..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in the severity of restless legs syndrome at bedtime, measured at the end of the three-month observation period. It uses Item 2 of the RLS-6 scale, an 11-point scale ranging from 0, “not present/completely satisfied,” to 10, “very severe/completely dissatisfied.” The endpoint is described as a mean change, with standard deviation as the measure of dispersion.
Bedtime symptoms are one part of the individual symptom profile that the RLS-6 is intended to capture. The scale also covers symptoms during the night and during the day, including periods of rest and daily activity. Focusing on bedtime therefore specifies a particular context and symptom dimension rather than treating all aspects of the condition as interchangeable. A change score compares each participant’s recorded value at follow-up with that participant’s baseline value; the mean summarizes the average change across the analyzed group.
As a general statistical point, a mean describes the center of a group’s values, while a standard deviation describes their spread. They answer different questions: an average change does not reveal whether individual changes were similar or widely dispersed. The registry record names the endpoint and analysis population but does not report the mean change or standard deviation. It therefore does not permit assessment of the observed direction, magnitude, or variability of the primary outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary outcome but does not report its numerical result. In particular, it gives no mean change in bedtime RLS severity and no standard deviation for that change. Without those values, the observed direction and magnitude cannot be described, and the precision of the estimate cannot be evaluated. The record also lists zero analyses, so it does not provide a posted statistical result for the primary endpoint.
The analysis population is stated as 564 participants in the Full Analysis Set, with all 564 included in the primary analysis. That count is distinct from the reported enrollment of 687 and the safety population of 684. These populations have different stated roles; the registry record does not explain the differences among their sizes in sufficient detail to reconcile them. A population count alone does not reveal the outcome distribution or how representative the analyzed participants were of everyone enrolled.
The study’s observational nature matters when interpreting any change over time. Participants received routine treatment rather than being described as randomly allocated to treatment options. General statistical interpretation: in an observational before-and-after study, change from baseline can reflect the treatment period and other influences, including natural symptom fluctuation, concurrent care, participant expectations, or differences in who has follow-up data. Without a randomized comparison, the record cannot establish how much change would have occurred over the same period under another treatment or no treatment.
The scale itself also affects interpretation. It is an 11-point measure of symptom severity at bedtime, with defined endpoints at 0 and 10. A group mean change would summarize the average shift on that scale, but would not by itself show the distribution of individual responses. The standard deviation would describe spread, but neither quantity is reported. The registry record also does not state a threshold for interpreting a change as clinically important.
LOCF was used for all outcomes, according to the registry description. This means that an earlier recorded value was carried forward for a participant when a later outcome value was unavailable, rather than using an unobserved later value. General statistical interpretation: this approach can make an analysis possible when follow-up measurements are missing, but it relies on assumptions about what the missing value would have been. Carrying a prior value forward does not establish that symptoms remained unchanged. The record does not report how many values were carried forward or why measurements were missing.
The safety counts should be read as observations among treated participants, not as comparative risks. Serious adverse events were reported for the Neupro® group, and other adverse events were also recorded. In the absence of a randomized comparator and further event details, these counts do not identify whether treatment caused an event or how the rates compare with another treatment. The record does not report deaths for the group.
Overall, the posted information describes study design, outcome definitions, analysis-population counts, and some safety observations. It does not provide the primary efficacy estimate or its uncertainty. Conclusions about the size of symptom change, its precision, and its clinical importance are therefore not supported by the numerical results in the registry record.
9. Statistical Methods Explained
The primary outcome is a continuous measure analyzed as a mean change. A continuous outcome can take a range of numerical values rather than being limited to categories such as event or no event. For each participant, a change score represents the follow-up measurement relative to baseline; the group mean summarizes those participant-level changes. The registry specifies change in Item 2 of the RLS-6 scale from baseline to the end of the three-month observation period. It does not report the mean change itself.
What does the mean describe?
As a general statistical concept, the mean is the arithmetic average of the analyzed values. For a change outcome, it summarizes the average within-participant change across the analysis group. The mean does not show whether most participants changed by a similar amount, whether changes differed substantially, or whether a small number of extreme values influenced the average. Those questions require information about the distribution of individual changes, which is not reported in the registry record.
The registry identifies standard deviation as the dispersion measure. As a general concept, a standard deviation describes how spread out individual measurements are around their mean. It is not the same as the uncertainty around the estimated mean. A standard deviation reflects variation among participants; a confidence interval, if reported, would describe uncertainty in an estimate under the statistical model used. No confidence interval or standard error for the primary outcome is reported in the registry record.
What does the scale measure?
The RLS-6 is described as an 11-point scale, from 0 to 10, intended to establish an individual severity profile at different times and in different situations. The primary analysis uses the bedtime item, not a combined score across all situations. The scale’s stated endpoints are 0, “not present/completely satisfied,” and 10, “very severe/completely dissatisfied.” The registry record does not give a threshold for interpreting the importance of a change, nor does it report the observed change distribution.
The endpoint is change from baseline to the end of the observation period. General statistical interpretation: using a change score can account for each participant’s starting measurement when describing follow-up change. However, a before-and-after change is not by itself a treatment-versus-control contrast. In an observational study, it cannot isolate treatment-associated change from other time-related influences without additional design and analysis assumptions. The registry record does not report an adjusted analysis that would address such influences.
How should LOCF be understood?
The registry says that Last Observation Carried Forward was used for all outcomes. In general, LOCF substitutes a participant’s last recorded outcome for a later outcome that is missing. It retains a value for the analysis rather than discarding that participant’s record for the particular outcome. The method effectively treats the last observed value as the value at the later assessment. That assumption may not match a participant’s unobserved course, especially when symptoms can change over time. The record does not report the extent of missing follow-up data, the number of carried-forward values, or reasons for missingness.
Missing-data methods can affect both the estimate and its uncertainty. General statistical explanation: when observations are unavailable, the observed data may differ systematically from the unobserved data. A method’s reliability depends on assumptions about that process and about how outcomes evolve after the last measurement. LOCF is a specified method, but its use alone does not show that missingness was harmless or that the carried-forward values were accurate. No sensitivity analysis is reported in the registry record.
What can the analysis population tell us?
The Full Analysis Set is reported as 564 participants, and all 564 are said to be included in the primary analysis. The registry description refers to treatment with rotigotine at least once and valid RLS-6 scores at baseline and at least one post-baseline assessment, but the available definition is incomplete. This count identifies who was included according to the record; it does not supply the primary outcome estimate. Enrollment was 687, while the safety population was 684. The registry record does not fully explain why the counts differ.
The registry lists zero analyses. As a result, no inferential result for the primary endpoint is available there: no test statistic, p-value, confidence interval, or numerical mean change is reported. General statistical explanation: a p-value, when used, measures how compatible data are with a specified null model under the assumptions of the analysis; it does not quantify the size or importance of an effect. A confidence interval communicates a range of values compatible with the data and model, and conveys precision. Neither can be interpreted when it is not reported.
How do the planning illustrations differ from trial design?
Planning illustrations based on an observed effect are not the same as the study’s original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. For continuous outcomes, the illustration is expressed as participants per arm for 80% power or other stated power levels when those calculations are available. These are planning quantities, not observed power and not evidence that the observational study had randomized arms.
The registry record does not report the study’s own sample-size justification, and it does not describe a randomized two-arm design. Any illustrative sample sizes based on the observed effect should therefore be treated as hypothetical planning scenarios rather than a reconstruction of the actual study plan. The primary numerical effect needed to evaluate such scenarios is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures and identifies a primary endpoint alongside secondary outcomes. The secondary topics include satisfaction with sleep, daytime RLS severity at rest, daytime RLS severity during activity, and daytime tiredness. The record lists zero analyses and does not provide numerical results for these outcomes. It also does not report whether a multiplicity adjustment, a prespecified hierarchy, or another strategy for interpreting multiple outcomes was used. Such a strategy is not reported in the registry record.
As a general statistical matter, evaluating multiple outcomes or multiple tests can increase the chance that at least one result appears notable by chance. An analysis plan may address that issue through prespecified priorities or statistical adjustments, but the registry record does not describe a plan of this kind. No conclusion about how the study handled multiplicity can be drawn from the list of outcomes alone.
The record states that LOCF was used for all outcomes. It does not report the amount of missing outcome data, the reasons for missingness, or the number of observations affected by LOCF. Nor does it report a sensitivity analysis comparing LOCF with another missing-data approach. As a result, the influence of missing measurements on the outcome estimates cannot be assessed from the registry information.
The Full Analysis Set included 564 participants, all of whom were included in the primary analysis. Its recorded definition refers to treatment exposure and valid baseline and post-baseline RLS-6 measurements, but the available description is incomplete. The registry record does not explain the full relationship between that population, enrollment of 687, and the safety population of 684. The sample-size justification, interim analyses, and detailed statistical analysis plan 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 |
|---|---|---|---|
| Neupro® | 8 | 684 | 1.2% |
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 |
|---|---|
| Neupro® | 121 of 684 |
Most frequent serious adverse event terms
| Event term | Organ system | Neupro® |
|---|---|---|
| Myocardial infarction | Cardiac disorders | 1 of 684 |
| Arrhythmia | Cardiac disorders | 1 of 684 |
| Diaphragmatic hernia | Gastrointestinal disorders | 1 of 684 |
| Ileus | Gastrointestinal disorders | 1 of 684 |
| Reflux oesophagitis | Gastrointestinal disorders | 1 of 684 |
| Herpes zoster | Infections and infestations | 1 of 684 |
| Pneumonia | Infections and infestations | 1 of 684 |
| Skeletal injury | Injury, poisoning and procedural complications | 1 of 684 |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | 1 of 684 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 684 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Neupro® |
|---|---|---|
| Nausea | Gastrointestinal disorders | 39 of 684 |
| Pruritus | Skin and subcutaneous tissue disorders | 23 of 684 |
| Headache | Nervous system disorders | 19 of 684 |
| Dizziness | Nervous system disorders | 19 of 684 |
| Rash | Skin and subcutaneous tissue disorders | 15 of 684 |
| Fatigue | General disorders | 14 of 684 |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | 14 of 684 |
| Application site erythema | General disorders | 8 of 684 |
| Sleep disorder | Psychiatric disorders | 8 of 684 |
| Hypertension | Vascular disorders | 7 of 684 |
Serious events with the highest arm-level rate: myocardial infarction (0.1%), arrhythmia (0.1%), diaphragmatic hernia (0.1%), ileus (0.1%), reflux oesophagitis (0.1%).
The registry record reports safety information for 684 participants in the Neupro® group. It records 8 participants with serious adverse events and 121 with other adverse events. These are counts in the treated group, not estimates of excess risk attributable to Neupro®. The record also lists myocardial infarction, arrhythmia, diaphragmatic hernia, ileus, reflux oesophagitis, and herpes zoster, each with a reported percentage of 0.1%.
These event figures describe observations made during the study. In general, an adverse event occurring during treatment is not, solely by that timing, established as caused by treatment. This distinction is especially important in a non-interventional study without a randomized control group. The record does not provide a like-for-like comparator for estimating how often such events would have occurred under another treatment or without Neupro®.
The serious adverse-event count and the listed event terms should not be treated as a complete account of clinical context or individual outcomes. The registry record does not report deaths for this group; the death value is not reported in the registry record. It also does not provide further information needed to compare event rates across treatment options or to attribute individual events to treatment.
12. What the Result Does, and Does Not, Mean
The record supports a description of the study’s purpose, design, outcome definition, and reported analysis populations. It indicates that the study examined routine use of Neupro® in restless legs syndrome and specified change in bedtime symptom severity as its primary outcome. It also documents use of LOCF and reports safety-event counts for the Neupro® group.
It does not report a numerical mean change in the primary outcome, its standard deviation, or a confidence interval. Therefore, the registry information does not establish the observed direction or size of change in bedtime severity, or how precisely that change was estimated. The registry record also does not report a statistical test or p-value for the primary endpoint. No conclusion about the primary result’s clinical importance can be drawn from the outcome definition alone.
The study was non-interventional and does not report a randomized control group. Even if a numerical before-and-after change were available, that change would describe what happened among analyzed participants over the observation period, not necessarily the effect caused by treatment. General statistical interpretation: without random assignment or an appropriate comparison and analysis, other influences on change cannot be cleanly separated from treatment-associated change.
The safety figures likewise describe recorded events among treated participants. They do not demonstrate that treatment caused those events, and the record does not provide comparative safety estimates against another group. The reported percentages for individual serious-event terms do not replace information about comparative risks or causal attribution.
The record leaves important questions unanswered, including the extent of missing data, the complete analysis plan, the rationale for the sample size, and the numerical results for the primary and secondary outcomes. The appropriate interpretation is therefore limited: the study’s aims and methods are documented, but its registry entry does not report the primary numerical result needed to quantify change.
13. Why This Trial Matters Statistically
This study illustrates a distinction that is central to biostatistical interpretation: a clearly defined outcome and analysis population do not substitute for a reported result. The registry specifies bedtime severity on the RLS-6 scale, a mean-change analysis, standard deviation as the dispersion measure, a three-month observation period, and LOCF for outcomes. Yet the numerical primary result is not reported. Without the estimate and its variability, readers cannot assess magnitude or precision.
It also illustrates why study design determines the questions that results can answer. Routine-practice observational data can describe treatment use and outcomes in a clinical setting. They do not, by themselves, provide the same causal comparison as randomized assignment. The study’s stated interest in switching and titration is relevant to real-life treatment practice, but the registry entry does not report detailed analyses of those topics.
The difference among enrollment, the Full Analysis Set, and the safety population is another statistical point worth noticing. Those populations are reported as 687, 564, and 684 participants, respectively. Their distinct counts signal that analysis populations may be defined differently for efficacy and safety, but the record does not fully explain the differences. Clear population definitions and accounting help readers understand which participants contribute to each result.
Finally, the stated use of LOCF makes missing-data assumptions part of interpretation. A named method is useful information, but the record does not report how much data were missing or whether alternative assumptions were examined. The example underscores that reporting methods, population counts, outcome estimates, and uncertainty together is necessary for readers to evaluate what an observational result can establish.
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 principal limitation for interpreting effectiveness is that the registry record does not report the numerical primary-outcome result. It gives no mean change or standard deviation for bedtime RLS severity, and no inferential estimate or uncertainty measure is listed. Secondary-outcome results are also not reported in the registry record. Consequently, the size, direction, variability, and precision of observed outcome changes cannot be assessed.
The study is described as non-interventional, and the registry record does not identify a randomized comparator or allocation method. Changes over time in a routine-practice population cannot, on their own, isolate the contribution of treatment from other influences. The stated intention to examine switching practice and titration does not establish that those topics were analyzed or that any particular pattern was observed.
LOCF was used for all outcomes, but the record does not report how much outcome information was missing, the reasons for missingness, or the number of values carried forward. The available Full Analysis Set definition is incomplete. The record also does not reconcile enrollment of 687 with the Full Analysis Set of 564 or the safety population of 684.
Further limitations of interpretation include the absence of a reported sample-size justification, interim-analysis information, and detailed statistical analysis plan. The record does not report a multiplicity strategy or sensitivity analyses for missing data. These items are not reported in the registry record, so their use should not be assumed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Non-interventional Study (NIS) in Patients With Restless Legs Syndrome in Daily Practise — NCT01113710.
- Registry record last updated 2012-09-28; status last verified 2012-08.
- Results first posted 2012-09-28.
- 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
NCT01113710 is a completed non-interventional study of Neupro® in patients with idiopathic restless legs syndrome. Enrollment was 687; the study began in 2010-05 and primary completion was recorded in 2011-07. The stated purpose was to describe effectiveness and safety under real-life conditions, including switching practice and titration.
The primary outcome was mean change in bedtime RLS severity from baseline to the end of the three-month observation period, measured with Item 2 of the RLS-6 scale. The Full Analysis Set and primary analysis each included 564 participants. LOCF was used for all outcomes. The registry record does not report the numerical primary result, its standard deviation, or a confidence interval.
Safety information was recorded for 684 participants in the Neupro® group, including 8 participants with serious adverse events and 121 with other adverse events. The study does not report a randomized control group, and the registry record lists zero analyses.