Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine (NCT00593606), a non-randomized phase 3 study. The primary outcome is Change in Pulse Rate (Supine, After 1 Minute).

2. Clinical Question

3. Trial Design

This was a Phase 3b, open-label, multicenter trial of switching from ropinirole therapy to the rotigotine transdermal system. It was non-randomized and used a single-group design, with no masking. The registry record identifies Parkinson’s disease as the condition and describes participants as having idiopathic Parkinson’s disease.

The trial enrolled 124 participants. The record lists a start date of 2007-07, primary completion in 2007-12, and status as completed. These dates describe the trial record; they do not establish the duration of each participant’s treatment. For the primary endpoint, the stated timeframe is baseline and 28 days.

Rotigotine patches were dispensed up to 8mg/24h. The dose was considered by the investigator to be equivalent to the dose of ropinirole the participant was currently taking. The record does not give a separate dosing algorithm or further details about how equivalence was determined.

With one treatment group and no random assignment, the design can describe changes and adverse events observed among participants who switched. It cannot directly distinguish a treatment-related change from changes that might have occurred over time, or from effects related to expectations, clinical care, or measurement. A protocol, sample-size justification, and detailed statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set, only patients with non-missing values were analyzed

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 in Pulse Rate (Supine, After 1 Minute), measured over Baseline, 28 days.

The primary endpoint is change in pulse rate measured supine, after 1 minute. Pulse rate is a continuous measure, so the registry record specifies the mean change and its standard deviation as the summary measures. The stated calculation is the 28 day value minus the baseline value. Under that definition, a positive change denotes a higher measured pulse rate at 28 days than at baseline, while a negative change denotes a lower measured pulse rate.

Measuring the same variable at baseline and follow-up permits the study to describe within-participant change over the stated interval. Reporting a mean summarizes the average change, while the standard deviation describes how much individual changes vary around that average. These summaries answer different questions: the mean describes the central tendency of change, and the standard deviation describes dispersion among observed changes.

The registry record does not report the mean change, standard deviation, number with evaluable measurements, or a confidence interval for this endpoint. Therefore, the direction and magnitude of the observed average change, and the precision with which it was estimated, cannot be determined from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as continuous and specifies mean change with standard deviation. This is a natural descriptive format for a variable such as pulse rate. The mean gives the average of the observed participant-level changes; the standard deviation describes the spread of those changes. Neither statistic is reported numerically for the primary endpoint in the registry record, so their interpretation is limited to what each measure represents.

What does a change score represent?

A change score is calculated for each participant by subtracting the baseline measurement from the follow-up measurement. The trial defines the primary change as the 28 day value minus baseline. Thus, the sign of a change reflects direction according to that subtraction order. The mean of participant-level changes then summarizes the average within-participant difference. This is distinct from comparing two unrelated group means, although the registry record does not provide the measurements needed to examine either calculation.

Change scores retain the paired nature of repeated measurements: each participant serves as the reference for their own baseline. General statistical interpretation still depends on the data and analysis choices, including how missing measurements are handled and whether the summary adequately describes the distribution. Those details beyond the stated non-missing-value population are not reported in the registry record.

Why report a standard deviation?

In general, the standard deviation describes dispersion among individual observations or changes around a mean. It is not the same as the uncertainty around the estimated mean. A standard deviation can be substantial even when a mean is estimated precisely, or modest when the available information is limited. Precision of a mean is more directly conveyed by a confidence interval or standard error; neither is reported for this endpoint in the registry record.

A confidence interval is generally used to show a range of estimates compatible with the observed data under the chosen model and assumptions. It can help readers assess both the direction and precision of an estimate. Since no interval or numerical estimate is reported, precision cannot be evaluated for the pulse-rate change. No p-value or formal hypothesis test for that endpoint is reported either.

What can a single-group design estimate?

In general, a single-group before-and-after study can describe observed change in the enrolled group over time. Without a concurrent control group, it cannot separate a treatment-associated change from time trends, changes in other care, measurement variability, or other influences. Randomization, when used in a comparative study, is intended to make treatment groups comparable on average; this trial was non-randomized and had no randomized comparison. Therefore, its design does not yield a controlled estimate of the difference attributable to switching.

The open-label design means masking was absent. In general, knowledge of treatment can affect participant reports, clinical decisions, or outcome assessment, depending on the measurement. Pulse rate is a measured physiological variable, but the record does not describe measurement procedures beyond the supine position and after 1 minute. It also does not report whether assessors were otherwise separated from treatment knowledge.

How should the planning illustration be read?

The registry record describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such an illustration is a hypothetical planning exercise for a two-arm comparison, not the design used in this single-group trial. The resulting participant counts are not reported in the registry record, and the assumptions do not establish that the trial was planned that way.

Sample-size calculations describe how much information might be needed under stated assumptions; they do not measure the probability that a completed study found a true effect. In particular, an illustration based on an observed effect is not observed power. Its interpretation depends on the assumptions and effect size used, and no actual planning rationale or prospective justification is reported in the registry record.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If variability is understated, uncertainty estimates can be too narrow and tests can be misleading. The endpoint is summarized as a mean and standard deviation, but the record does not provide enough numerical detail to assess the distribution or whether an alternative model was considered. No specific adjustment for over-dispersion is reported.

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(112)
m   <- c(2)
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  112  2.000  9.400  0.240  3.760

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary pulse-rate change and secondary outcomes covering UPDRS Parts I, II, III, and IV; Parkinson’s Disease Sleep Scale, Epworth Sleepiness Scale, Parkinson’s Disease Non-Motor Symptom Assessment Scale, and Clinical Global Impression. It lists 93 outcome measures and no analyses. The record does not describe a multiplicity adjustment, a hierarchy of secondary outcomes, or a plan for interpreting several outcomes together.

In general, evaluating many outcomes can increase the chance of at least one apparently unusual result arising by chance when each is tested separately. A prespecified testing hierarchy or adjustment can address that issue, but neither is reported in the registry record. No numerical results for the listed secondary outcomes are included in the registry record describing the posted results, so their estimates and uncertainty cannot be interpreted.

The primary endpoint population is described as the Safety Set, with only participants who had non-missing values analyzed. The record does not report the number with non-missing primary measurements, the extent or reasons for missingness, or any imputation method or sensitivity analysis. It also does not report whether the endpoint analysis followed another defined population. Missing-data methods matter because an analysis of available measurements can be misleading if missingness is related to participant characteristics or outcomes.

The enrollment was 124, while safety counts are based on 116 participants at risk. These counts do not establish the number contributing primary endpoint measurements. The registry record does not explain the difference between the enrollment total and the safety denominator.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports one Rotigotine group, with 116 participants at risk for serious adverse events and 0 affected. For other adverse events, 116 were at risk and 45 were affected. These counts describe participants in the trial group; they are not comparisons with another treatment, because no concurrent comparator group was used.

In general, a serious adverse event is a category defined by regulatory seriousness criteria, rather than simply an event that is intense or unpleasant. The registry record’s serious-event count should be read according to that category. The list of top serious terms is empty, and the number of deaths is not reported in the registry record. An unreported death count is not the same as a reported count of zero.

The counts describe how many participants were affected, not the number of separate event episodes or how long participants were observed. The record does not give further details about event timing, severity, relatedness, or duration. A count of 0 serious events in this group does not establish that serious events cannot occur, and the 45 participants with other adverse events cannot be interpreted as a comparative risk. The registry record does not provide a control group or a basis for estimating a relative safety difference.

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

The trial addresses a practical statistical question: how to describe pulse-rate change over time after participants with idiopathic Parkinson’s disease switched from ropinirole to rotigotine patches. It specifies a primary measure, a direction for calculating change, and a 28 day follow-up point. It also provides safety counts for the Rotigotine group. These details make the intended descriptive focus clear.

The numerical primary result is not reported in the registry record. Without the mean change, its standard deviation, and an uncertainty interval, readers cannot assess the magnitude, direction, or precision of the average change. The endpoint definition alone is not evidence that pulse rate changed in either direction.

The design also limits the kind of conclusion the posted results could support. A single-group, non-randomized, open-label study has no concurrent control against which to compare changes. Even if numerical before-and-after results were available, observed change would not by itself show what caused it or what would have occurred without switching. The record does not report information that would resolve that limitation.

The safety data show 0 participants affected by serious adverse events among 116 at risk and 45 affected by other adverse events among 116 at risk. These are counts from one group, with no comparative estimate. The registry record does not report the number of deaths. As a result, the posted safety information is descriptive and cannot establish a difference in risk relative to another treatment.

The record therefore supports a description of the study design, intended endpoint, and stated safety counts. It does not report enough numerical outcome information to assess the primary change or its precision, and its single-group design does not provide a controlled comparison. Any stronger interpretation would require results or methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its question and design are not the same thing. The question concerns change after a treatment switch, while the design is a single-group, non-randomized follow-up. A before-and-after measure can describe what happened among observed participants, but without a concurrent control it cannot isolate the effect of switching from other influences over time.

The endpoint definition also illustrates why the direction of subtraction matters. Here, change is explicitly the 28 day measurement minus baseline. That definition fixes how positive and negative values would be interpreted, but the registry record does not report the numerical result. A clearly defined outcome is useful, yet it does not replace the estimate and its uncertainty.

The distinction between spread and precision is important as well. The record specifies a standard deviation, which would describe variability in participant-level changes. A confidence interval would address uncertainty about the estimated mean. Neither numerical summary is reported, so the reader cannot assess variability or precision from the primary endpoint description.

Finally, the registry record separates the endpoint population from the safety counts: the primary outcome includes only those in the Safety Set with non-missing values, while the adverse-event denominator is 116. The count enrolled was 124. These figures should not be treated as interchangeable analysis populations. The record does not state how many participants contributed primary measurements or explain missingness. Recognizing those distinctions helps prevent a descriptive record from being read as a complete comparative effectiveness or safety analysis.

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 the main outcome is that the registry record does not report a numerical estimate of pulse-rate change, its standard deviation, or an uncertainty interval. It also does not report a p-value or a formal test for that outcome. The direction, magnitude, and precision of the primary result therefore cannot be assessed.

The design was single-group, non-randomized, and open-label. There was no concurrent control group, so observed change cannot be separated from changes over time or other influences through a controlled comparison. The registry record does not report a comparator, randomization procedure, or masking.

The primary endpoint population is limited to the Safety Set with non-missing values, but the number contributing measurements and the reasons for missing data are not reported. No missing-data method or sensitivity analysis is reported. The enrollment total of 124 and safety denominator of 116 do not establish the endpoint analysis sample size.

The record does not report a sample-size justification, a detailed statistical plan, a multiplicity approach, or a hierarchy for secondary outcomes. It lists numerous outcome measures but no analyses. These omissions limit assessment of whether the posted outcome reporting follows a prespecified plan. The registry record also does not report further measurement procedures, adverse-event timing or relatedness, or a death count. These are limits on interpretation of the recorded information, not evidence that any particular procedure or analysis was or was not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Tolerability Trial of Switching From Ropinirole to Rotigotine — NCT00593606.
• Registry record last updated 2014-10-02; status last verified 2011-10.
• Results first posted 2009-05-27.
• 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

NCT00593606 is a completed Phase 3b, open-label, multicenter, non-randomized, single-group trial of switching from ropinirole to rotigotine patches in participants with idiopathic Parkinson’s disease. Enrollment was 124. Rotigotine was dispensed up to 8mg/24h at an investigator-selected dose considered equivalent to the participant’s current ropinirole dose.

The primary endpoint was change in supine pulse rate after 1 minute from baseline to 28 days, defined as the 28 day value minus baseline and intended to be summarized by mean and standard deviation. Its numerical result is not reported in the registry record. The record describes the primary population as the Safety Set with non-missing values.

For the Rotigotine group, 0 of 116 participants at risk were affected by serious adverse events, and 45 of 116 were affected by other adverse events. Deaths are not reported in the registry record. No concurrent control group was used.