Placebo-controlled Study in Patients With Parkinson's Disease to Evaluate the Effect of Rotigotine on Non-motor Symptoms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Placebo-controlled Study in Patients With Parkinson's Disease to Evaluate the Effect of Rotigotine on Non-motor Symptoms (NCT01300819), a randomized phase 4 study. The primary outcome is Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score.

2. Clinical Question

The clinical question concerns non-motor symptoms, which are assessed separately from the motor symptoms captured by the Unified Parkinson's Disease Rating Scale Part III. The primary measure combines ratings across multiple symptom domains, rather than isolating a single complaint. This makes the question broad: whether the overall score changed differently between groups during the maintenance period.

The trial's stated objective was to demonstrate improvement in non-motor symptoms compared with placebo. Statistical interpretation is narrower than that objective: it asks what the posted group summaries and sponsor analysis indicate about the difference in mean change, and how uncertain that estimate is. Neither the objective nor the observed direction of the group means alone establishes a treatment effect.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase IV study comparing rotigotine with placebo in patients with idiopathic Parkinson's disease. The official title describes the trial as multicenter and double-blind as well as placebo-controlled; the registry's masking classification is quadruple. The registry record does not specify which people or roles were masked, nor does it describe the randomization method or allocation concealment.

The registry lists enrollment of 349 and marks the study completed. The recorded start was 2011-02, and primary completion was 2012-10. The sponsor was UCB Pharma. The arm descriptions do not give dose, administration schedule, or other treatment details, so those features are not reported in the registry record.

The primary outcome was change in total Nonmotor Symptoms Scale score from baseline, identified as Day 1, to the end of 12-week maintenance, identified as Day 84. The primary analysis population was the Full Analysis Set: treated subjects with a baseline and post-baseline NMSS measure, following the intention-to-treat principle as described in the record. The group counts in the primary outcome are specific to that outcome analysis and should not be read as the overall enrollment.

The sponsor reported an ANCOVA analysis for the primary outcome, expressed as a mean difference in final values. The registry record does not describe the covariates, model specification, missing-data procedure, or whether any interim analyses were planned or conducted. The original sample-size justification and its design assumptions are also not reported in the registry record. Planning calculations based on the posted effect are separate illustrations, not a reconstruction of the trial's original design.

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: Eligibility was assessed during the Screening Period, which lasted up to 4 weeks prior to the Baseline Visit. Eligible subjects returned for a Baseline Visit, during which all Baseline assessments were performed and then the subject was randomized to either Rotigotine or Placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.

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.

Population: Baseline characteristics are presented by the Randomized Set (RS), which is defined as all subjects that signed informed consent and were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score, measured over From Baseline (Day 1) to end of 12-week Maintenance (Day 84).

The primary endpoint was change from baseline to the end of maintenance in total Nonmotor Symptoms Scale score. The scale is described in the registry as a validated measure of the frequency and severity of non-motor symptoms in Parkinson's disease. An investigator rates symptoms across nine domains, including cardiovascular symptoms, sleep and fatigue, mood and cognition, perceptual problems, attention and memory, gastrointestinal symptoms, urinary symptoms, sexual function, and miscellaneous symptoms.

Severity is rated from 0 (none) to 3 (severe), while frequency is rated from 1 (rarely) to 4 (very frequent). The total score ranges from 0 to 350. A negative change from baseline to the end of maintenance indicates improvement. Because the total combines multiple symptom domains, it provides a broad summary of non-motor symptom burden; it does not show whether every domain changed in the same way.

Change from baseline is used to describe movement in the measure over the treatment period, while comparing the groups helps distinguish their average changes from change observed under placebo. The endpoint is continuous and the posted arm summaries are means with standard deviations. The clinical meaning of a particular score difference, including what size would be important to patients, is not reported in the registry record.

7. Results Posted in the Registry

• Rotigotine: mean -23.10 versus -19.10 on control; difference -4.00 (95% CI -9.38 to 1.38), standardized effect d = -0.17; z-test p = 0.145.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rotigotine: mean -5.70 versus -3.60 on control; difference -2.10 (95% CI -3.94 to -0.26), standardized effect d = -0.26; z-test p = 0.026.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Rotigotine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rotigotine: mean -5.90 versus -2.60 on control; difference -3.30 (95% CI -6.01 to -0.59), standardized effect d = -0.29; z-test p = 0.017.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Rotigotine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rotigotine: mean -1.10 versus -1.20 on control; difference 0.10 (95% CI -0.56 to 0.76), standardized effect d = 0.03; z-test p = 0.768.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rotigotine and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies secondary outcomes covering motor symptoms, health-related quality of life, and several non-motor symptom domains. Across the secondary results described, the pattern is not uniform: some estimates are in the direction of greater improvement with rotigotine, while other comparisons show little separation between group averages. This variety is expected when distinct measures capture different aspects of health and symptom experience.

Secondary outcomes provide context for the primary result, but they do not replace it. The primary endpoint was a total non-motor symptom score, whereas secondary measures include specific symptom domains and other constructs. An apparent difference on a secondary measure does not establish a difference on the primary measure, and a primary result with an interval spanning zero is not resolved simply by looking at secondary findings.

Multiplicity is important because examining many outcomes creates more opportunities for apparently notable results to arise by chance. The registry record lists 12 outcome measures and 12 analyses, but does not report a multiplicity adjustment or a hierarchy for interpreting secondary findings. The secondary p-values should therefore be treated as unadjusted unless the registry explicitly reports otherwise. A nominally small p-value in a secondary analysis carries less confirmatory weight when many outcomes are considered and the correction strategy is not reported.

The secondary results are best viewed as supportive or exploratory context, not as a collection of independent confirmations. Their interpretation also depends on the endpoint definitions, analysis populations, missing-data handling, and statistical models, several of which are not described in the registry record. The posted secondary analyses cannot, on their own, determine whether any observed contrast is clinically important.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score
• Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39)
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory,
• Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract

9. Statistical Interpretation

10. Statistical Methods Explained

The outcome is continuous: it is a numerical score, and the posted group summaries use means and standard deviations. A mean describes the average change within a group. A standard deviation describes how spread out individual changes are around that average. It is not the uncertainty interval for the mean and does not imply that every participant changed by an amount close to the average.

What does the unadjusted comparison represent?

The recalculated comparison subtracts the placebo mean change from the rotigotine mean change using the posted summary statistics. It is a simple, unadjusted comparison of group means, not the sponsor's ANCOVA model. A negative contrast means the mean change was more negative in the rotigotine group; for this scale, the registry says negative change indicates improvement. The contrast is a group-level estimate, not a statement about the change experienced by a particular participant.

In a randomized parallel-group trial, a between-group comparison is used to assess whether average outcome changes differ across assigned groups. Randomization can support a fair comparison, but it does not remove uncertainty in the observed estimates. The posted outcome counts differ from overall enrollment because they refer to participants contributing to this outcome analysis; the record's definition of the primary analysis population also requires both baseline and post-baseline measurements.

What does a p-value say?

A p-value measures how incompatible the observed data are with a specified null model, under the assumptions used for the analysis. A smaller p-value generally indicates greater tension with that null model. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The primary unadjusted recalculation reports p = 0.145, while the sponsor's ANCOVA reports p = 0.147. Both should be read alongside their estimates and confidence intervals, rather than as stand-alone verdicts.

The registry identifies the sponsor's method as ANCOVA, or analysis of covariance. In general, ANCOVA models an outcome while accounting for one or more covariates, and can produce an adjusted group contrast. The record reports the method and its mean difference in final values, but does not describe the covariates, model form, or details of the analysis. It would therefore be inappropriate to assert which specific adjustments were used or to reproduce the sponsor's model from the reported summaries.

Why can the two estimates differ?

The simple recalculation uses posted group change means and their variability. The sponsor's reported analysis is an ANCOVA of final values. Because these are not the same analysis, their estimates and uncertainty measures need not match exactly. The registry record does not report enough model detail to attribute the difference to a particular covariate or modeling choice. The record does not flag a discrepancy between the recalculation and sponsor analysis; the sponsor's own analysis remains the trial's reported analysis.

How should standard deviations and standard errors be distinguished?

A standard deviation describes variability among individual outcome changes. A standard error describes uncertainty in an estimated statistic, such as a group mean. The primary arm summaries report standard deviations, while the recalculation also uses uncertainty estimates for the group means. These quantities answer different questions: variability among participants is not the same as precision of the estimated average. A group mean may be estimated more precisely when its contributing observations provide more information, even if individual outcomes remain variable.

General statistical methods often rely on assumptions about the distribution of outcomes or estimates. The registry does not report diagnostic checks or assumptions for the primary ANCOVA. For this continuous outcome, the posted summary-statistics recalculation is not a substitute for access to participant-level data, which would allow fuller assessment of distributions, covariates, and missingness.

Why does the analysis population matter?

The primary analysis is described as the Full Analysis Set and follows the intention-to-treat principle, but its stated definition includes only treated subjects with baseline and post-baseline NMSS measurements. This description identifies the population used; it does not explain how missing post-baseline values were handled or whether any imputation was used. The registry record does not report those details. The result therefore needs to be understood in relation to the stated available-measure requirement, rather than assumed to include every randomized participant in every analysis.

Finally, the statistical estimate addresses average change during the specified maintenance period. It does not establish the cause of every participant's change, and it does not address outcomes or time points that were not analyzed. Statistical evidence, clinical relevance, and the completeness of reporting are related but separate considerations.

11. Confidence Intervals and Precision

A confidence interval gives a range of estimates compatible with the observed data under the analysis assumptions. It communicates precision: a narrower interval indicates less uncertainty about the estimate, while a wider interval indicates more. It is not a range containing every participant's outcome, and it is not a guarantee that the true value lies inside the interval.

For the primary unadjusted recalculation, the mean difference was -4.0 and the 95% confidence interval ran from -9.377 to 1.377. The interval spans zero, so it includes no mean difference as well as contrasts in either direction. This is consistent with the unadjusted p-value of 0.145. The estimate points toward a more negative mean change for rotigotine, but the interval shows that the point estimate is not precise enough to exclude no difference.

The sponsor's ANCOVA estimate was -3.58, with a 95% confidence interval from -8.43 to 1.26. That interval also spans zero. Its interpretation is broadly similar to the unadjusted interval, while the endpoints and estimate differ because the analyses differ. The registry record does not provide the full model specification needed to further assess the sponsor interval's construction.

Confidence intervals are conditional on the analysis and its assumptions. They do not account automatically for multiple outcomes, unreported analysis choices, missing data, or possible biases. A confidence interval that includes zero does not prove the absence of an effect; likewise, a point estimate on one side of zero does not prove a difference. Precision must be considered together with the design, endpoint, analysis population, and reporting limitations.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the trial's original design. For these continuous outcomes, the figures are participants per arm, not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a future study to have an 80% chance of detecting the specified effect under the planning assumptions, if that effect is real. The 90% power column gives the corresponding planning number for a 90% chance. These are design probabilities under a particular assumed effect and analysis model, not guarantees about a future result.

Rows describing planning for 100%, 75%, or 50% of the observed effect represent progressively smaller target effects. Smaller effects are harder to distinguish from random variation, so the calculations require more participants per arm to reach the same target power. For example, for the primary comparison, planning around 100% of the observed effect gives 551 participants per arm for 80% power and 738 for 90% power; planning around 50% gives 2,204 for 80% and 2,950 for 90%.

These estimates are not observed power. They are illustrations of how sample requirements change with the assumed effect and chosen power target, and should not be interpreted as evidence about whether the completed trial was adequately planned. They also do not account for design features not included in the stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -4.000; pooled standard deviation σ = 23.696.
2. n = 2 × (1.96 + 0.842)² × 23.696² / -4.000² = 550.9, rounded up to 551 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -4                      # observed difference in means
sigma <- 23.6960574455233                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1300819)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 551 (80% power), 738 (90% power)
 75% of observed effect: n per arm = 980 (80% power), 1,312 (90% power)
 50% of observed effect: n per arm = 2,204 (80% power), 2,950 (90% power)
power.t.test: 551.9 
Simulated power at n = 551 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor reported the primary outcome using ANCOVA, with a mean difference in final values of -3.58, a 95% confidence interval from -8.43 to 1.26, and p = 0.147. The simple recalculation from posted group change summaries gives a mean difference of -4.0, a 95% confidence interval from -9.377 to 1.377, and p = 0.145. Both estimates point in the same direction, and both confidence intervals include zero.

These results are close in broad statistical interpretation, but they are not interchangeable. The recalculation is an unadjusted comparison of summary statistics. The sponsor's ANCOVA is the trial's reported analysis and concerns final values; the registry record does not describe its covariates or full model. Differences between the estimates and intervals can arise because the analyses use different information and methods, but the record does not report enough detail to explain the difference further.

The registry record does not flag a discrepancy between the recalculation and sponsor result. The sponsor's analysis should therefore be read as the trial's primary reported analysis, while the recalculation offers a transparent, unadjusted perspective from the posted summaries. Neither analysis supplies evidence that the groups are equivalent, and neither interval excludes a zero contrast.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 12 analyses, including the primary outcome and secondary outcomes. It does not report whether the sponsor used a multiplicity adjustment, a prespecified testing hierarchy, or another strategy to control the chance of false-positive findings across multiple comparisons. The secondary results should therefore not be interpreted as if each were the sole planned test. Without a reported approach, nominal p-values do not account for the full set of outcomes examined.

The record also does not report whether the primary analysis was prespecified in a statistical analysis plan, whether interim analyses took place, or how any such analyses would have been handled. Those details should not be inferred from the completed status or the reported outcome values.

The primary population is described as the Full Analysis Set: treated subjects with a baseline and post-baseline NMSS measure, following the intention-to-treat principle. That definition gives useful information about who contributed to the primary outcome analysis, but it does not state how missing outcome values were handled. The registry record does not report the extent or pattern of missing data, the method used to address missingness, or sensitivity analyses examining alternative assumptions.

These omissions matter because missing outcomes and the handling of multiple comparisons can affect uncertainty and the strength of conclusions. The reported estimates remain interpretable as the posted analyses, but the record does not support assuming that all missing values were imputed, that no interim looks occurred, or that multiplicity was controlled. The covariates and detailed specifications of the sponsor's ANCOVA are also not reported, limiting independent assessment of that adjusted model.

16. 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: death (0.8%), spinal column stenosis (0.8%), urinary tract infection (0.8%), acute cerebral infarction (0.8%), hemiparesis (0.8%).

The registry reports serious adverse events for groups described as at risk: 4 affected participants among 125 at risk in the placebo group, and 8 among 223 at risk in the rotigotine group. It also lists other adverse events affecting 21 among 125 at risk in the placebo group and 66 among 223 at risk in the rotigotine group. These are descriptive counts with their reported at-risk group sizes, not a test of whether the groups differ.

The listed serious-event terms include Death, Spinal column stenosis, Urinary tract infection, Acute cerebral infarction, Hemiparesis, and Decubitus ulcer, each shown with 0.8%. The registry's separate death-count field is not reported in the registry record. The listed term percentages do not provide enough detail to reconstruct event counts for each term or to determine whether an event was considered related to treatment.

These safety summaries should be read cautiously. The registry record does not report detailed event definitions, timing, duration, severity breakdowns, or a statistical comparison for these counts. Counts alone do not establish causation or support a conclusion about comparative safety.

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

The primary result describes an average change in total non-motor symptom score over the maintenance period in the analysis population. Rotigotine's observed mean change was more negative than placebo's, and the scale description associates negative change with improvement. The estimated mean difference was also negative. However, the confidence interval includes zero, and the sponsor's ANCOVA interval does too. The posted primary analyses therefore do not establish a clear between-group difference.

This is not proof that the treatments have identical effects. A result that does not clearly distinguish the groups can reflect uncertainty, including uncertainty about contrasts in either direction. Nor does the favorable direction of a point estimate establish that rotigotine produces a meaningful benefit. The registry record does not report a threshold for clinical importance, so the clinical meaning of the estimated score contrast cannot be determined from statistical evidence alone.

The total NMSS score combines multiple symptom domains. A group average does not show whether every domain changed similarly, whether most participants improved, or how responses varied between individuals. Secondary outcomes provide additional measures, but their multiplicity and incomplete methodological detail limit the strength of conclusions drawn from them.

The trial record concerns the stated population, endpoint, and period through the end of 12-week maintenance. It does not establish durability beyond that period, effects in unreported subgroups, or outcomes that were not included in the posted analyses. The safety counts are descriptive and do not establish whether events were caused by study treatment. In short, the posted data describe a direction of average change and its uncertainty; they do not justify a definitive claim of treatment benefit, no effect, equivalence, or comparative safety.

18. Why This Trial Matters Statistically

This trial illustrates why a clinical outcome should be interpreted through both its estimated effect and its uncertainty. The primary group means favor a more negative change for rotigotine, but the confidence interval includes zero. Reporting only the direction of the means would omit the central statistical limitation: the data do not pin down the between-group contrast with enough precision to rule out no difference.

It also illustrates how different analyses of the same trial can answer related but non-identical questions. The simple recalculation compares posted changes without adjustment, while the sponsor reports an ANCOVA estimate for final values. Their broadly similar direction is reassuring about the descriptive pattern, but their estimates should not be collapsed into one number or treated as methodologically identical. More detailed model reporting would help readers understand the adjusted analysis.

The endpoint itself matters. A total symptom score summarizes multiple domains, while individual secondary measures describe narrower outcomes or different aspects of health. A broad measure can be useful for an overall question, but it may conceal variation among domains and participants. Secondary comparisons add context, yet multiple testing means they require cautious interpretation.

Finally, trial records are most useful when they report not only estimates but also analysis populations, missing-data methods, multiplicity plans, and model details. The registry identifies the primary population and sponsor method, but leaves important design and analysis details unreported. Recognizing those boundaries helps distinguish what the posted data support from what remains uncertain.

19. 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.

Several trial-specific reporting limits affect interpretation. The registry's arm descriptions do not specify rotigotine dose or administration schedule, and do not provide further details about placebo procedures. Although the trial is described as quadruple-masked and its official title calls it double-blind, the roles covered by masking are not reported in the registry record. The randomization method and allocation concealment are also not described.

The primary endpoint is a total score spanning multiple symptom domains. The record does not report a threshold for a clinically important difference, participant-level response summaries, or domain-level results for the primary analysis. The group means and standard deviations cannot show how many individuals improved or whether changes were concentrated in particular domains.

The sponsor's ANCOVA is identified by method and its reported estimate, but the model covariates and specification are not reported. The record also does not describe missing-data handling, the pattern of missing measurements, sensitivity analyses, or the basis for the Full Analysis Set beyond its stated measurement requirements. These gaps limit assessment of how robust the primary estimate is to analysis choices.

Multiplicity procedures for the many outcome measures are not reported, and the registry does not describe an analysis hierarchy. The original sample-size assumptions, interim analyses, and detailed statistical plan are also not reported in the registry record. Finally, the primary outcome covers the maintenance period only; the registry entries do not establish longer-term outcomes or findings for populations beyond the study's described patients.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Placebo-controlled Study in Patients With Parkinson's Disease to Evaluate the Effect of Rotigotine on Non-motor Symptoms — NCT01300819.
• Registry record last updated 2014-05-09; status last verified 2014-04.
• Results first posted 2014-05-09.
• 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.

23. Record Summary

NCT01300819 was a completed randomized, quadruple-masked, parallel-group Phase IV trial of rotigotine versus placebo in patients with idiopathic Parkinson's disease. The registry lists enrollment of 349 and describes the study as multicenter. The primary endpoint was change in total NMSS score from baseline to the end of 12-week maintenance, with negative change defined as improvement.

The primary unadjusted recalculation estimated a mean difference of -4.0, with a 95% confidence interval from -9.377 to 1.377. The sponsor's ANCOVA estimate was -3.58, with a 95% confidence interval from -8.43 to 1.26. Both intervals include zero. The record does not report important details including the original sample-size justification, missing-data methods, multiplicity strategy, or full ANCOVA specification.