Long-term Extension of RECOVER- Long-term Effect of the 24h Transdermal Delivery of Rotigotine in Subjects With Idiopathic Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Extension of RECOVER- Long-term Effect of the 24h Transdermal Delivery of Rotigotine in Subjects With Idiopathic Parkinson's Disease (NCT00519532), a na phase 3 study. The primary outcome is Change From Baseline in UPDRS III Score at Week 13 (End of Maintenance).

2. Clinical Question

3. Trial Design

This is a phase 3b, multicenter, multinational, open-label extension trial of rotigotine transdermal delivery in people with idiopathic Parkinson’s disease. The registry lists the model as single group and allocation as NA. There is no concurrent control arm identified, so the design is not a randomized treatment comparison. The registry describes rotigotine as the intervention and the arm as Rotigotine Transdermal Patch.

The stated objective includes long-term assessment of motor function, sleep quality, nocturnal symptoms, and non-motor symptoms. It also includes evaluation of the patch’s long-term safety and tolerability. The named primary endpoint is change from baseline in UPDRS III score at week 13, described as the end of maintenance. Secondary outcomes include change from baseline in the Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) and change from baseline in the number of nocturias at week 13.

The registry lists enrollment as 84, a start date of 2007-07, and primary completion as 2009-05. Its current status is terminated. The reason for termination, the duration of treatment beyond the stated endpoint, and the extent of follow-up are not reported in the registry record. The title identifies this study as an extension of RECOVER, while the primary-endpoint description defines baseline as the first titration visit (T1) of SP915. Details about the relationship between enrollment in this extension and participation in any earlier study are not reported in the registry record.

Because participants and investigators were not masked and there is no concurrent comparator, changes over time cannot be separated from other influences using this design alone. The registry record does not report the protocol details needed to assess treatment adherence, concomitant care, or the precise conduct of visits.

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: Participant Flow information belong to the Enrolled Set (ES). Baseline Characteristics are described for the Full Analysis Set (FAS).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS).

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in UPDRS III Score at Week 13 (End of Maintenance), measured over Baseline (baseline SP915) and week 13 (End of maintenance).

The primary endpoint is change from baseline in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS III) score at week 13, the end of maintenance. The registry describes UPDRS III as an accepted and validated scale for assessing motor function in Parkinson’s disease. Each element is scored from 0 to 4, with 0 defined as normal and 4 representing severe abnormalities. The endpoint is reported as a mean, with standard deviation identified as the dispersion measure.

Change from baseline expresses how a participant’s score at the specified follow-up differs from the baseline score. As a general interpretation, the direction and size of a mean change describe the average score movement in the assessed population, while the standard deviation describes the spread of participant-level changes around that average. Neither measure alone shows how individual participants changed.

The baseline is defined in the registry record as the first titration visit (T1) of SP915. The endpoint population is the Full Analysis Set. The record names the endpoint and its assessment time, but does not report the mean change, standard deviation, number with endpoint data, or a confidence interval. Without those results, the magnitude and precision of the week 13 change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

The named primary endpoint is a mean change in UPDRS III score from baseline to week 13 in the FAS. In general, a mean summarizes the average observed change across the participants included in an analysis. It does not imply that every participant changed by that amount. The standard deviation, which the registry identifies as the dispersion measure, describes how widely individual changes vary around the mean. A standard deviation is not the same as the uncertainty in the estimated mean.

The registry record does not report the observed mean change or standard deviation. It also does not state the number of participants with both baseline and week 13 measurements. Therefore, the estimate itself and the amount of information behind it cannot be evaluated from the posted results.

What would a confidence interval add?

As a general statistical concept, a confidence interval gives a range of values compatible with the data and the analysis under the method’s assumptions. It communicates estimation uncertainty in a way that a point estimate alone cannot. A narrow interval indicates greater precision than a wide interval, although precision is not the same as freedom from bias. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be judged.

A p-value, if reported, would address how compatible the data are with a specified null hypothesis under an analysis model. It would not measure the size or clinical importance of an effect, and it would not correct limitations of an uncontrolled design. No primary-endpoint p-value or analysis is reported in the registry record.

Why does the design matter for interpretation?

In a single-group extension, the primary endpoint is a change over time within the assessed group, rather than a contrast between concurrently randomized groups. General interpretation of such a change must account for the fact that other influences can also vary over time. Open-label conduct can additionally affect reported or assessed outcomes through expectations or behavior. These are design considerations, not evidence that a particular bias occurred.

Since allocation is listed as NA and the model as single group, the record does not support a randomized between-group treatment effect estimate. A before-and-after mean change, if reported, would be descriptive of the analyzed participants in this study setting. It would not establish what would have happened to the same participants over the same period under another treatment or no treatment.

What can the planning assumptions tell a reader?

The record describes sample-size illustrations based on 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. These are planning assumptions for illustrations, not evidence that this extension trial used those design choices. The record explicitly characterizes the illustrations as computed from the observed effect, not as the trial’s own design. They must not be read as observed power or as the trial’s enrollment target.

The record also distinguishes the interpretation of planning outputs: for time-to-event outcomes, the illustrations concern total events; for other outcomes, they concern participants per arm. That general distinction does not turn the single-group extension into a two-arm comparison. The actual numerical planning results are not stated in the registry entries, and the primary observed effect needed to assess them is not reported alongside the endpoint.

Why can variability matter?

As a general concept, variability affects the precision of an estimated mean. When participant-level changes differ substantially, the average may be less precisely estimated than when changes are more consistent, all else being equal. For count outcomes, over-dispersion means that variation exceeds what a simple model assumes; accounting for it can affect standard errors and intervals. The record names secondary outcomes involving a score and a number of nocturias, but does not report a statistical model or an over-dispersion assessment. No such modeling choice should be inferred.

For this trial, the practical conclusion is limited: endpoint definitions are available, but the primary outcome estimate, its uncertainty, the detailed analysis method, and the handling of incomplete observations are not reported in the registry record. General statistical concepts can explain what those quantities would mean, but cannot substitute for the missing trial-specific results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Rotigotine")
n   <- c(76)
m   <- c(-5.8)
sp  <- c(9.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Rotigotine  76  -5.800  9.400  -7.948  -3.652

11. Multiplicity, Missing Data and Analysis Populations

The record names one primary endpoint and two secondary outcomes: change from baseline in NADCS at week 13 and change from baseline in the number of nocturias at week 13. It also lists four outcome measures overall, but does not identify the remaining measures in the registry record for this analysis. The registry lists zero analyses. It does not report a multiplicity adjustment, a hierarchy among outcomes, or a statistical plan for interpreting multiple tests. It is therefore not possible to determine whether or how the trial accounted for the chance of false-positive findings across several outcomes.

Missing-data handling is not reported in the registry record. In particular, the record does not describe whether participants without a week 13 measurement were excluded, whether missing values were imputed, or whether a sensitivity analysis was conducted. These choices can affect the analyzed population and the interpretation of a change-from-baseline estimate. No specific approach should be assumed.

The primary-endpoint population is named as the FAS, but the registry does not define the FAS membership criteria or state how that population was used in practice. The number of participants contributing to the primary analysis is not reported. Enrollment is listed as 84; that does not establish how many had usable endpoint data. The registry record also does not provide a statistical analysis plan or analysis population definitions for the secondary outcomes.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: femoral neck fracture (3.6%), atrial fibrillation (1.2%), atrioventricular block third degree (1.2%), vomiting (1.2%), reflux oesophagitis (1.2%).

The registry’s adverse-event entry lists the Rotigotine group with 84 at risk for serious adverse events and 16 affected. For other adverse events, it lists 84 at risk and 55 affected. These are descriptive counts in a single-group trial, not comparative estimates against a control group. They do not establish that rotigotine caused an event or that an event would not have occurred without treatment.

The serious-event terms listed include Femoral neck fracture at 3.6%, and Atrial fibrillation, Atrioventricular block third degree, Vomiting, Reflux oesophagitis, and Inguinal hernia at 1.2% each. The registry record does not provide further event narratives or an account of how investigators assessed relatedness. The percentages should be read as registry-reported frequencies, not as evidence about causation.

Deaths are not reported in the registry record. The record also does not explain the reason for trial termination. The available safety summary therefore cannot establish the full safety profile, distinguish treatment-related events from other events, or support a comparison with another treatment.

13. What the Result Does, and Does Not, Mean

The record establishes that an open-label, single-group extension trial evaluated 24-hour transdermal rotigotine in idiopathic Parkinson’s disease and specified change in UPDRS III score at week 13 as its primary endpoint. It also records objectives concerning sleep quality, nocturnal and non-motor symptoms, and long-term safety and tolerability. These registry entries describe the trial’s purpose and planned assessment, not its efficacy findings.

The primary endpoint result is not reported in the registry record. No mean change, standard deviation, confidence interval, or p-value is available in the registry record for this analysis. Therefore, the size and precision of any observed motor-function change cannot be stated. The absence of a posted estimate is not evidence that there was no change, and it is not evidence that a change occurred.

Even if a before-and-after change estimate were available, the single-group design would not provide a concurrent treatment contrast. A within-group change can describe the observed course of scores, but alone cannot isolate the contribution of treatment from other changes over time. The open-label design is another limitation to interpretation. These points concern what the design can establish, not a conclusion about the actual direction of the outcome.

The safety entry provides counts and selected serious-event terms, but the lack of a comparator means those data cannot show whether event frequency differs from another treatment or no treatment. They also do not establish causation. The registry record does not report deaths or the reason for termination, and it does not provide enough detail to assess the completeness of safety follow-up.

The most defensible reading is that the registry documents the study design and endpoint definitions, while leaving the primary statistical result and key analysis details unavailable. Conclusions about the magnitude, precision, or causal interpretation of an outcome would go beyond what the record reports.

14. Why This Trial Matters Statistically

This trial is statistically notable as an example of an extension study whose endpoint is defined more clearly than its posted result. The record specifies the UPDRS III measure, the baseline definition, the week 13 assessment, the analysis population label, and the intended summary as a mean with standard deviation. Those details help identify what the primary estimate was meant to describe. Yet without the estimate and its uncertainty, readers cannot assess the observed change or its precision.

The single-group, open-label design also makes the distinction between change over time and a comparative treatment effect especially important. A change from baseline may be useful as a description of the course observed in the enrolled group, but it does not by itself provide the counterfactual comparison required to attribute that change to treatment. This is a general design principle, not a judgment about the trial’s result.

The registry record further illustrates why analysis populations and missing-data methods matter. It names the FAS but does not define its membership or report how many participants contributed to the endpoint. It does not describe missing-data handling or a statistical analysis plan. Thus, readers cannot determine whether the available measurements represent all enrolled participants or how incomplete follow-up was addressed.

Finally, the safety information is descriptive and the trial status is terminated, with no reason stated. Keeping these registry entries distinct from efficacy evidence helps prevent overinterpretation. The record can inform readers about the question and design, but it does not provide enough statistical results to quantify the primary outcome or support a treatment comparison.

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 primary limitation for interpreting this trial record is the absence of a reported primary-endpoint estimate. Although the endpoint is defined as change in UPDRS III score at week 13, the mean change and standard deviation are not reported. The registry also lists zero analyses. Without the result, its uncertainty, and the analysis details, the primary statistical finding cannot be evaluated.

The study is open-label and single-group, with no concurrent comparator. Any within-group change would be vulnerable to influences that occur over time and could not be interpreted as a randomized treatment contrast. The registry record does not report masking, adherence, concomitant treatments, or additional design details that might help characterize these influences.

The record names the FAS but does not state its operational definition, the number analyzed for the primary endpoint, or how missing outcomes were handled. It also does not report whether analyses adjusted for baseline values or used sensitivity analyses. These omissions limit assessment of the estimate’s robustness and the population to which it applies.

The status is terminated, but the reason is not reported in the registry record. The record does not describe the extent of follow-up or whether safety reporting was complete. Deaths are not reported. The listed serious-event counts and terms cannot establish causal attribution in the absence of a comparator and further event detail.

Although the registry identifies two secondary outcomes and four outcome measures overall, it does not provide the complete outcome list or a multiplicity plan in the registry record. This limits interpretation of any collection of outcome findings and does not permit assessment of selective reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Extension of RECOVER- Long-term Effect of the 24h Transdermal Delivery of Rotigotine in Subjects With Idiopathic Parkinson's Disease — NCT00519532.
• Registry record last updated 2014-10-27; status last verified 2010-09.
• Results first posted 2010-04-02.
• 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.

19. Record Summary

NCT00519532 is a phase 3b, multicenter, multinational, open-label, single-group extension trial of rotigotine transdermal patch in idiopathic Parkinson’s disease. The registry lists enrollment as 84, start as 2007-07, primary completion as 2009-05, and status as terminated.

The primary endpoint is change from baseline in UPDRS III score at week 13, with baseline defined as the first titration visit (T1) of SP915 and the FAS named as the population. The registry record does not report a numerical primary result or analysis. It lists secondary outcomes for NADCS and number of nocturias at week 13.

The safety entry lists serious and other adverse-event counts for the Rotigotine group and selected serious-event terms. Deaths and the reason for termination are not reported in the registry record. The design and posted information do not support a randomized treatment comparison.