Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine (NCT00474058), a randomized phase 3 study. The primary outcome is Change in Early Morning UPDRS Part III Score.

2. Clinical Question

The central statistical question is whether the observed difference between groups is sufficiently distinct from sampling variation to support a difference in the measured outcome. The primary endpoint is a continuous score, so the posted results describe group means and a mean difference. A negative change represents a lower score at follow-up than at baseline. Because the scale assigns higher values to more severe abnormalities, the direction of change is relevant when interpreting the group summaries, while the between-group estimate indicates the size and direction of the comparison.

The trial also recorded outcomes concerning nocturnal akinesia, dystonia, and cramps, and the number of nocturias. These broaden the clinical questions beyond the primary motor-function score, but they do not replace the designated primary question. Their results should be read as additional evidence, with attention to the uncertainty and the fact that multiple outcomes were examined.

3. Trial Design

This was a Phase 3, randomized, parallel-group trial comparing rotigotine with placebo. The official title describes it as multicenter and multinational, double-blind, and placebo controlled; the registry’s masking classification is quadruple. The arms received rotigotine transdermal patch or placebo transdermal patch. The trial was sponsored by UCB Pharma and is recorded as completed.

The registry records an enrollment of 287. The primary outcome summaries include 178 participants in the rotigotine group and 89 in the placebo group. These are the arm-specific numbers attached to the posted primary outcome summaries; the registry does not explain in the results record why the numbers contributing to that outcome differ from the overall enrollment. The primary analysis population is described as the Full Analysis Set with Last Observation Carried Forward.

The primary outcome timeframe was from baseline to the end of maintenance, after 4 weeks of maintenance. The trial’s objective included early-morning motor function and sleep disorders, with further evaluation of nocturnal and non-motor symptoms. The two posted secondary outcomes concern the Nocturnal Akinesia, Dystonia, and Cramps Score and the number of nocturias.

The recorded start was 2007-05 and primary completion was 2009-03. Those dates describe the registry record; they do not establish the duration of participation for an individual or the timing of each assessment. Details of eligibility criteria, treatment titration, other visits, and the original sample-size justification are not reported in the registry record.

Random allocation and masking are important design features because they can reduce systematic differences in group assignment and expectations. The record identifies these design features but does not give further operational details about how allocation was generated or concealed, who was included in the masking classification, or whether masking was assessed during the trial.

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 shows all 287 subjects who has been enrolled and randomized. 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) with Last Observation Carried Forward (LOCF).

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 Early Morning UPDRS Part III Score, measured over From baseline to end of maintenance (after 4 weeks maintenance).

The primary endpoint is change in Early Morning UPDRS Part III score from baseline to the end of maintenance, after 4 weeks of maintenance. UPDRS Part III is described in the registry as an accepted and validated sum score covering 14 items used to assess motor function in Parkinson’s disease. Each item is scored from 0 to 4, with 0 representing normal function and 4 representing severe abnormalities. The endpoint therefore summarizes motor findings as a continuous measure rather than as a count of participants who did or did not meet a threshold.

The registry reports the mean and standard deviation for each group. The mean change describes the average movement in scores over the assessment period; the mean difference compares that movement between the rotigotine and placebo groups. A negative change indicates a lower follow-up score than baseline. Given the stated scoring direction, lower scores correspond to fewer or less severe abnormalities on the measured items. This interpretation concerns the score itself and is not, by itself, a conclusion about every aspect of Parkinson’s disease or a participant’s overall experience.

A continuous endpoint can capture degrees of change across the scale, which is useful when the research question concerns average change rather than only a categorical response. Its interpretation still depends on the scale, the study population, the analysis method, and the uncertainty around the estimated difference. The registry record does not report a threshold for a clinically important change, so the posted mean difference cannot be classified against such a threshold from this record alone.

7. Results Posted in the Registry

• Rotigotine: mean -7.00 versus -3.90 on control; difference -3.10 (95% CI -4.98 to -1.22), standardized effect d = -0.41; z-test p = 0.001.

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 in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS)

• 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 -1.30 versus -0.90 on control; difference -0.40 (95% CI -0.94 to 0.14), standardized effect d = -0.21; z-test p = 0.148.
• 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.

Change in Number of Nocturias

• 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 -0.30 versus -0.20 on control; difference -0.10 (95% CI -0.42 to 0.22), standardized effect d = -0.08; z-test p = 0.535.
• 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 two posted secondary outcomes extend the trial’s assessment from early-morning motor function to nocturnal symptoms: one concerns nocturnal akinesia, dystonia, and cramps, and the other concerns the number of nocturias. In the posted group summaries, the direction of mean change is generally consistent with a larger reduction for rotigotine than placebo. The uncertainty is less conclusive than for the primary endpoint: the unadjusted recalculated intervals for both secondary comparisons include zero.

The registry also reports sponsor ANCOVA analyses for the secondary outcomes. Their inferential results do not produce an identical pattern across outcomes. This reinforces that secondary findings should be considered outcome by outcome and in relation to the analysis used, rather than combined into a single conclusion about all nocturnal symptoms. The registry record does not state a hierarchy among the secondary outcomes or identify one as confirmatory.

Secondary outcomes can help describe whether the primary finding is accompanied by changes in related measures, but they generally carry less weight than the designated primary endpoint when many outcomes are examined. Each additional comparison creates another opportunity for a result to appear statistically notable by chance. Whether and how the analysis accounted for this issue is not reported in the registry record. The reported secondary p-values should therefore be understood as unadjusted for any multiplicity unless the record states otherwise; no such adjustment is described.

The secondary outcomes do not independently establish the primary endpoint result, and the primary result does not settle each secondary question. The measures differ in what they assess, and the registry does not report a method for combining them. Taken together, they offer supporting descriptive context, but uncertainty and multiplicity limit the strength of conclusions drawn from the secondary findings.

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

• Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS)
• Change in Number of Nocturias

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, so the main summaries are group means and standard deviations. A mean gives the average score change in a group, while a standard deviation describes the spread of participant values around that average. Neither statistic fully describes the individual data, but together they provide a compact account of location and variability. The registry reports the number contributing to each group summary as well as those descriptive statistics.

What does the mean difference represent?

The mean difference compares the average change in the rotigotine group with the average change in the placebo group. A negative difference in this setting indicates a more negative average change for rotigotine. Because the endpoint is change in score and higher UPDRS Part III scores represent more severe abnormalities, the direction can be interpreted in relation to the score’s stated scale. The estimated difference is a group-level contrast; it is not an estimate of the change experienced by every individual.

The recalculated comparison uses posted group summary statistics to form an unadjusted estimate. It does not incorporate participant-level information or adjustment for baseline values and other covariates. Its standard error and confidence interval reflect the summary-statistic calculation, rather than the sponsor’s ANCOVA model. Such a recalculation is useful for understanding the basic contrast, but it cannot reproduce details of a model that require individual data or information about its specification.

What does a confidence interval communicate?

In general, a confidence interval gives a range of estimates compatible with the observed data under the statistical method and assumptions used. Its width reflects precision: a narrower interval indicates greater precision than a wider interval on the same measurement scale. It is not a range containing every participant’s response, and it does not give the probability that the true value lies in the specific calculated interval.

For the primary recalculation, the 95% confidence interval is -4.983 to -1.217. For the sponsor-reported ANCOVA result, it is -5.37 to -1.73. Both intervals are entirely negative, so both analyses place the estimated group contrast in the same direction. Their different endpoints reflect that the estimates come from different methods. The registry does not provide enough model detail to determine precisely which analytical choices account for the difference.

How should p-values be read?

In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model and its assumptions. It is not a measure of effect size, clinical importance, or the probability that the null hypothesis is true. The recalculated primary p-value is 0.001, while the sponsor’s reported ANCOVA result is p < 0.001. These are evidence measures associated with their respective analyses, not independent estimates of the size of the difference.

The registry labels the sponsor analysis as ANCOVA and reports a mean difference in final values. ANCOVA is a general analysis-of-covariance approach that can compare groups while accounting for one or more covariates. The specific covariates, model terms, handling of baseline values, and other implementation details are not reported in the registry record. It would therefore be inappropriate to assume a particular adjustment specification based on the method label alone.

Why can unadjusted and ANCOVA estimates differ?

In general, an unadjusted comparison and a covariate-adjusted comparison may differ because they use information differently and can have different precision. An adjusted estimate depends on the selected model and covariates, while the summary-statistic recalculation depends on the reported group means, standard deviations, and sample sizes. A difference between estimates does not by itself establish an error. The registry record reports both analyses, and the sponsor’s analysis is the trial’s reported inferential analysis.

The recalculation is explicitly unadjusted and uses the posted summaries. It is not a replacement for the sponsor’s analysis and does not supply information absent from the registry, such as model diagnostics, treatment of covariate data, or participant-level missingness patterns. No discrepancy is flagged in the registry record.

Why does variability matter?

Standard deviations describe variation among participant measurements. Greater variation generally makes a group mean less precisely estimated when sample size is held constant. The precision of a contrast also depends on the number of observations in each group and on the analysis method. The posted standard deviations for the primary outcome are 7.6 for rotigotine and 7.3 for placebo. These values describe spread, not uncertainty in the group means themselves; the confidence interval is the more direct summary of uncertainty about the between-group contrast.

General statistical methods also distinguish standard deviation from standard error. A standard deviation describes variability among observations; a standard error describes the sampling variability of an estimate. Confusing the two can lead to incorrect interpretations of how tightly the group mean or treatment contrast is estimated.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that the observed variation exceeds what a simple count model assumes. It can affect standard errors and confidence intervals if the model does not accommodate the extra variability. This is a general concept rather than a reported feature of this trial. The posted nocturia outcome is summarized as a mean and standard deviation, and the registry does not report an over-dispersion assessment or a count-model analysis.

The methods record is therefore informative but incomplete. It identifies the primary analysis population, the LOCF approach, and the sponsor’s ANCOVA method, but does not report the detailed analysis plan, covariates, model checks, or alternative analyses. Those omissions limit how fully an independent reader can reproduce or evaluate the sponsor’s analysis from the registry record alone.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate the group difference. The primary unadjusted recalculation has a 95% confidence interval from -4.983 to -1.217. The sponsor-reported ANCOVA interval runs from -5.37 to -1.73. Both intervals are on the negative side of zero, which means that the uncertainty ranges reported for these analyses do not include no difference. The confidence intervals nevertheless cover a range of possible magnitudes, rather than identifying one exact value.

The two intervals should not be compared as if they came from one common calculation. The unadjusted interval is recalculated from posted summary statistics, whereas the sponsor interval comes from the reported ANCOVA. The estimates are close in direction, but their precise values and widths depend on the method used. Details of the ANCOVA specification are not reported in the registry record, limiting a fuller explanation of the difference in precision.

A confidence interval is not an interval for individual participant outcomes and does not indicate that most participants had changes within its limits. It describes uncertainty about a group-level contrast under the analytical assumptions. The standard deviations show that individual measurements varied substantially around each group’s mean, while the interval quantifies uncertainty about the mean difference.

Precision also does not settle clinical importance. The registry does not report a threshold for a clinically important difference in Early Morning UPDRS Part III score. Consequently, the interval can be used to describe statistical uncertainty and direction, but cannot establish from this record alone whether every value within it represents a meaningful change in clinical terms.

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 figures are planning illustrations based on the observed effect, not the original design justification for the trial. All figures in this setting are participants per arm. They are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column indicates the planned number of participants per arm under which the calculation would have an 80% chance of detecting the specified effect if that effect and the planning assumptions were correct. The 90% column represents a higher target probability of detection under the same kind of assumptions. Higher target power generally requires a larger planned sample size. These descriptions are general interpretations of power and do not guarantee that a future study will achieve its target.

Each row changes the effect assumed for planning. The full observed effect is one scenario; the 75% and 50% scenarios assume smaller effects. Smaller effects require more participants to distinguish the group contrast from sampling variation at the same significance and power targets. For example, for the primary endpoint, planning for 75% of the observed effect gives 164 participants per arm for 80% power and 219 participants per arm for 90% power. These are illustrations derived from the observed effect, not evidence about the power of the completed trial.

A sample-size curve is read as a relationship between the effect size being targeted and the sample size required under the specified assumptions. Moving toward smaller targeted effects generally means that more participants are needed. The curve is a planning aid: its implications depend on the assumed allocation, significance level, model approximation, and target effect. It does not predict the effect that another trial will observe.

This is not observed power. The figures do not retrospectively measure the probability that the completed trial detected its result, and they do not establish what assumptions guided the actual trial design. The primary-outcome analysis numbers and the planning illustrations answer different questions: one describes the posted trial comparison, while the other explores hypothetical sample sizes under stated planning 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 = -3.100; pooled standard deviation σ = 7.502.
2. n = 2 × (1.96 + 0.842)² × 7.502² / -3.100² = 91.9, rounded up to 92 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 <- -3.1                      # observed difference in means
sigma <- 7.50170798162055                     # 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(474058)
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 = 92 (80% power), 124 (90% power)
 75% of observed effect: n per arm = 164 (80% power), 219 (90% power)
 50% of observed effect: n per arm = 368 (80% power), 493 (90% power)
power.t.test: 92.9 
Simulated power at n = 92 per arm: 0.796 (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 registry reports the sponsor’s primary analysis as ANCOVA, with a mean difference in final values of -3.55, a 95% confidence interval from -5.37 to -1.73, and p < 0.001. This is the trial’s reported analysis. The separate recalculation uses the posted group means, standard deviations, and sample sizes to estimate an unadjusted mean difference of -3.1, with a 95% confidence interval from -4.983 to -1.217 and an unadjusted p-value of 0.001.

Both analyses report a negative difference, and both confidence intervals exclude zero. Their estimates are not identical because they are not the same analysis: the recalculation is unadjusted, while the registry identifies the sponsor’s method as ANCOVA. The registry does not report the ANCOVA covariates or full model specification, so the difference cannot be attributed to a particular adjustment from this record alone.

No discrepancy is flagged in the registry record. The sponsor’s analysis should be read as the trial’s own reported inferential result; the recalculation is a transparent, simple comparison based on summary statistics and is useful as a complementary check. Neither result should be treated as though it were the other method’s estimate, and the recalculation does not supersede the sponsor analysis.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines more than one outcome, comparison, or analysis. If each test is considered separately without adjustment, the chance of obtaining at least one apparently notable result across a collection of tests can increase. This is a general statistical concern, not a claim that any particular posted result is false. The registry lists two secondary outcomes and reports four outcome measures and four analyses. It does not report a multiplicity adjustment, a testing hierarchy, or a plan for controlling an overall error rate.

The primary outcome is identified separately from the secondary outcomes, which helps distinguish the main research question from additional questions. However, the registry record does not state whether the primary endpoint was the only confirmatory test or how the other outcomes were intended to affect interpretation. In the absence of a reported multiplicity strategy, secondary p-values should be treated cautiously and should not be read as if each were the sole planned test.

For the primary analysis, the registry identifies the Full Analysis Set with Last Observation Carried Forward. LOCF is a missing-data approach in which an earlier observed value is carried forward for a later assessment when that later value is missing. In general, this method makes assumptions about the relationship between the carried-forward value and the unobserved outcome. The registry does not report the amount or timing of missing data, the reasons for missingness, or sensitivity analyses using alternative assumptions.

The record does not state whether LOCF was used for the secondary analyses. It also does not provide a detailed definition of the Full Analysis Set, a participant flow accounting for all randomized participants, or an account of exclusions from each outcome analysis. The different numbers attached to outcome summaries indicate that the analyzed sets are not identical, but the reasons for the differences are not reported in the registry record.

These reporting gaps constrain assessment of robustness. Without missing-data rates, the treatment of incomplete assessments, and sensitivity analyses, readers cannot determine how much the estimates might change under other plausible missing-data assumptions. The registry does identify key features of the primary analysis, but it does not provide enough detail to reconstruct the complete analysis plan or establish how multiplicity and missing observations were addressed across every reported outcome.

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: oedema peripheral (1.0%), chronic lymphocytic leukaemia (1.0%), basal cell carcinoma (1.0%), cerebrovascular accident (1.0%), panic attack (1.0%).

The registry reports serious adverse events for 10 of 191 participants at risk in the rotigotine group and 5 of 96 participants at risk in the placebo group. It also reports other adverse events affecting 70 of 191 participants at risk in the rotigotine group and 21 of 96 participants at risk in the placebo group. These are the posted counts and denominators; they are not the efficacy-analysis sample sizes.

The record lists several serious adverse-event terms at 1.0% each: oedema peripheral, chronic lymphocytic leukaemia, basal cell carcinoma, cerebrovascular accident, panic attack, and completed suicide. These terms are reported as serious-event listings; the registry record does not establish whether an event was caused by treatment. The number of deaths is not reported in the registry record.

Adverse-event counts should be read as safety summaries, not as proof of a causal relationship or as a complete account of event timing, duration, severity, or participant-level histories. The registry record does not provide those details in the registry record reported for these results. The at-risk denominators also differ from the primary outcome analysis numbers, so the safety and efficacy summaries describe different analysis populations.

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

The posted primary results show a negative between-group difference in change in Early Morning UPDRS Part III score, with the rotigotine group having a larger average reduction than the placebo group. Both the sponsor-reported ANCOVA analysis and the unadjusted recalculation have confidence intervals that exclude zero. This describes the statistical evidence for a group difference in the measured endpoint over the specified maintenance period.

The result does not mean that every participant improved, that all aspects of motor function changed in the same way, or that the average score difference predicts an individual’s outcome. Group means can coexist with considerable variation among participants. The registry does not report individual trajectories or the proportion of participants meeting a responder threshold.

The result also does not establish the clinical importance of the estimated magnitude. The registry record does not report a clinically important difference threshold for the primary score. Statistical evidence that a group contrast differs from zero is distinct from evidence about whether the size of that contrast matters to patients or clinicians.

The trial compared a rotigotine patch with a placebo patch in a defined population and over a stated assessment period. Its findings should be understood within that design and outcome. They do not, on their own, establish effects beyond the measures and timeframe recorded, nor do they answer every question about sleep, nocturnal symptoms, non-motor symptoms, or safety. The secondary results have their own uncertainty and are subject to the interpretive limits of multiple comparisons.

Finally, the record identifies an analysis population and LOCF approach but does not provide detailed missing-data sensitivity analyses or the full ANCOVA specification. The reported estimates are therefore best interpreted as results under the analyses documented in the registry, rather than as estimates proven insensitive to all alternative analytical choices.

18. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through several statistical layers rather than through a p-value alone. The endpoint is a continuous scale, so the group means describe average change and the mean difference provides a direct between-group contrast. The confidence interval then shows the range of estimates compatible with each analysis, while the standard deviations describe variation among participants.

It also illustrates the value of separating a sponsor-reported model from a simple recalculation. The ANCOVA result is the trial’s reported analysis, while the recalculation from summary statistics is unadjusted. Their broadly consistent direction is informative, but the estimates are not identical and should not be conflated. The registry’s lack of detailed model specification limits the extent to which the adjusted analysis can be independently reproduced.

The secondary outcomes show why the primary endpoint needs to remain distinct from exploratory or additional questions. Related outcomes may provide context, yet their uncertainty and the lack of a reported multiplicity strategy make it harder to treat them as a unified confirmatory result. A pattern across measures can be suggestive without removing the need to account for outcome selection and repeated testing.

The sample-size illustrations offer another statistical lesson: planning depends strongly on the effect assumed to be worth detecting. Smaller target effects require larger samples under otherwise similar planning assumptions. Because these illustrations use the observed effect and do not reproduce the trial’s original design process, they should not be mistaken for evidence of the trial’s planned or achieved power.

Overall, the registry record supports a careful reading of the primary group contrast while also exposing limits in reporting detail. Recognizing both the information in the estimates and the gaps in the analysis record is central to responsible interpretation.

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.

The registry record does not report the original sample-size justification or the assumptions used to plan this trial. The planning illustrations based on the observed effect cannot fill that gap, because they are not a reconstruction of the trial’s design calculations.

The sponsor analysis is identified as ANCOVA, but the model specification, covariates, assumptions, and diagnostics are not reported. This limits independent evaluation of how adjustment affected the estimate. The recalculation from group summaries offers a simpler unadjusted comparison, but it cannot replace participant-level analysis or reproduce the sponsor model.

The primary analysis population is described as the Full Analysis Set with LOCF, but the registry record does not report missing-data counts, reasons for missingness, or sensitivity analyses under alternative assumptions. The exact reasons that outcome-specific sample sizes differ are also not reported in the registry record. It is therefore difficult to assess the potential impact of missing outcomes or exclusions from the posted summaries alone.

The registry does not report a multiplicity strategy for the primary and secondary analyses, nor does it provide a stated hierarchy for interpreting secondary outcomes. This limits the weight that can be assigned to nominal secondary findings. In addition, the record does not report a clinically important-change threshold for the primary endpoint, so statistical estimates cannot be translated into a registry-defined judgment of clinical importance.

The safety information summarized in the registry does not provide event timing, duration, severity details beyond the serious-event classification, or causal attribution. Deaths are not reported in the registry record. These limitations concern what the record documents and should not be taken as evidence that an event did or did not occur beyond the information recorded.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine — NCT00474058.
• Registry record last updated 2015-06-22; status last verified 2015-05.
• Results first posted 2010-04-12.
• 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

The registry records a completed, randomized, quadruple-masked, parallel-group Phase 3 trial of rotigotine transdermal patch versus placebo transdermal patch in Parkinson’s disease, with enrollment of 287. The primary endpoint was change in Early Morning UPDRS Part III score from baseline to the end of maintenance, after 4 weeks of maintenance.

The primary group summaries and both reported analyses indicate a negative mean difference. The sponsor-reported ANCOVA result and the unadjusted recalculation have confidence intervals that exclude zero, while the secondary outcomes present a less consistent pattern of statistical evidence. The registry also reports serious and other adverse-event counts for both groups.

Important details, including the original sample-size justification, full ANCOVA specification, multiplicity strategy, and missing-data sensitivity analyses, are not reported in the registry record. The posted estimates are therefore most appropriately interpreted in light of the stated outcome, analysis methods, and reporting limits.