Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease (NCT00823836), a randomized phase 3 study. The primary outcome is Mean Change From Week 0 (Baseline) in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score at the Final Assessment Point (FAP) (up to Week 24) in the Non-Inferiority Verification Phase.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 3 trial sponsored by GlaxoSmithKline. The registry record describes an enrollment of 302 participants and a comparison of ropinirole PR/XR with ropinirole IR, both in conjunction with L-dopa, in advanced Parkinson’s disease. The study status is completed. The recorded start was 2009-03 and primary completion was 2010-12.

Random allocation assigns participants to groups by chance, while double masking is intended to keep participants and relevant study personnel unaware of assignment. A parallel-group design follows separate groups receiving the compared regimens rather than switching the same participants between them. These are general descriptions of the design terms; details of the randomization procedure, masking arrangements, treatment duration, and handling of treatment changes are not reported in the registry record.

The primary endpoint was assessed in the Per Protocol Set, not the full enrollment group. The record describes this set as excluding participants from the Full Analysis Set when protocol violations led investigators to assess them as unsuitable for the efficacy assessment. The primary summaries include 141 participants in the Ropinirole PR-Ropinirole PR group and 133 in the Ropinirole IR-Ropinirole PR group. The safety summaries use different denominators: 156 and 146, respectively. The registry record does not give a complete participant flow explaining these analysis populations and denominator differences.

The endpoint was collected at Week 0 and at the final assessment point, which could be up to Week 24. The registry says on-treatment last observations within the phase were carried forward as final assessment values. Further details of the trial’s original sample-size justification, randomization sequence, interim analyses, and prespecified 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.

Before assignment: A total of 157 participants who were enrolled in the Non-Inferiority Verification (NV) Phase entered into the Long-term Phase after completing the Prolonged Release/Extended Release (PR/XR) Switching Phase according to the study design. The remaining participants entered into the Down-titration Phase after completing the PR/XR Switching Phase.

NV and PR/XR Switching Phases

Reasons for not completing this period:

Long-term Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per Protocol Set (PPS): participants with exclusion from the Full Analysis Set (FAS) of those violating the study protocol and assessed to be excluded from the assessment of drug efficacy. On-treatment last observations within the phase were carried forward as FAP values of the phase. FAP values do not include values of Weeks 0, 1, and 2.

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 Mean Change From Week 0 (Baseline) in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score at the Final Assessment Point (FAP) (up to Week 24) in the Non-Inferiority Verification Phase, measured over Week 0 and FAP (up to Week 24).

The primary endpoint was mean change from Week 0 in the Japanese Unified Parkinson’s Disease Rating Scale (UPDRS) Part III total score at the final assessment point, up to Week 24, in the non-inferiority verification phase. The registry describes Part III as a motor examination covering 27 items. Each item is scored from 0 to 4, the maximum total score is 108, and a higher score indicates more severe Parkinson’s disease symptoms. Change was defined as the total score at the final assessment point minus the Week 0 total score.

A change score expresses how a participant’s measured score differed from baseline, while the group mean describes the average change among participants included in the analysis. This endpoint focuses on motor examination, one defined part of the broader UPDRS assessment. As a general statistical point, a continuous score can retain information about the size and direction of measured changes rather than reducing outcomes to categories such as responder or non-responder.

The record states that participants who withdrew before Week 2 and had only one observation for Part III were excluded from this analysis. It also describes carrying forward on-treatment last observations within the phase as final assessment values. The clinical importance threshold for a change in this score and the non-inferiority margin are not reported in the registry record, so the size of a numerical difference cannot be classified against those criteria from the record alone.

7. Results Posted in the Registry

• Ropinirole IR-Ropinirole PR: mean -11.00 versus -10.80 on control; difference -0.20 (95% CI -2.08 to 1.68), standardized effect d = -0.03; z-test p = 0.835.

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.

Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

• 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:
  • Ropinirole IR-Ropinirole PR: mean -0.30 versus -0.20 on control; difference -0.10 (95% CI -0.38 to 0.18), standardized effect d = -0.08; z-test p = 0.487.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ropinirole IR-Ropinirole PR and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

• 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:
  • Ropinirole IR-Ropinirole PR: mean -2.90 versus -2.60 on control; difference -0.30 (95% CI -1.20 to 0.60), standardized effect d = -0.08; z-test p = 0.515.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ropinirole IR-Ropinirole PR and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase

• 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:
  • Ropinirole IR-Ropinirole PR: mean -3.80 versus -4.70 on control; difference 0.90 (95% CI -0.70 to 2.50), standardized effect d = 0.19; z-test p = 0.269.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ropinirole IR-Ropinirole PR and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover additional Japanese UPDRS domains, including Part I and Part II scores in “On” and “Off” states. For the secondary endpoint summaries available in the record, group mean changes are generally close in the displayed domains, while the direction and size of the group contrast are not uniform across every measure. These outcomes add context about other aspects of the assessment but do not replace the primary Part III motor endpoint.

The secondary findings are broadly compatible with the primary summaries in that they do not present a consistent pattern of large separation between groups across the reported measures. This is a descriptive reading, not evidence that all outcomes are equivalent. The secondary measures have different scales, assessment conditions, and analysis populations, and their estimates have their own uncertainty. The numeric summaries should be interpreted within each endpoint’s definition rather than compared as if all score changes were interchangeable.

The registry record lists 61 secondary outcomes, and the trial reports many outcome measures. A large set of outcomes raises the general possibility of multiplicity: when many hypotheses are tested, some nominally notable findings can arise by chance. No multiplicity adjustment or hierarchy for interpreting secondary outcomes is reported in the registry record. The recalculated secondary p-values are unadjusted, so they carry less confirmatory weight than a prespecified primary analysis and should be treated as exploratory evidence.

No sponsor-reported analyses are listed for the secondary summaries included in the available results. Their relationship to the primary result is therefore best described as additional descriptive context, not independent confirmation of the primary comparison or proof of a non-inferiority conclusion.

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

• Percentage of Responders on the Japanese UPDRS Part III Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase
• Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase
• Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase
• Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase
• Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase
• Japanese UPDRS Part I Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
• Japanese UPDRS Part II (at "On") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
• Japanese UPDRS Part II (at "Off") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, and the registry reports group means and standard deviations. A mean is the arithmetic average within a group. A standard deviation describes how dispersed individual scores are around that group’s mean; it is not the uncertainty of the mean itself. The number of participants contributing to each summary also matters when assessing how precisely the mean is estimated.

What does the unadjusted re-calculation represent?

The re-calculated contrast compares the posted group means without adjustment for other variables. It is expressed as the IR group mean minus the PR group mean: -0.2 points. The associated interval is -2.081 to 1.681, and the unadjusted p-value is 0.835. These are simple re-calculations from posted summary statistics, rather than a reconstruction of the trial’s full analysis. They do not account for covariates or reproduce the sponsor’s ANCOVA. No covariate-adjusted re-calculation is available from the information in the registry record.

As a general explanation, an unadjusted comparison describes the difference between group summaries as recorded, whereas an adjusted analysis estimates a contrast while accounting for included variables according to its model. Adjustment can affect the estimate and its uncertainty. The variables, model specification, and adjustment details for the sponsor analysis are not reported in the registry record, so its ANCOVA cannot be independently reproduced from the posted summaries.

How should the ANCOVA result be read?

The sponsor-reported method is ANCOVA, and the result is described as a median difference (net) of 0.34, with a 95% confidence interval from -1.41 to 2.09 and p = 0.702. ANCOVA is a general method for comparing groups while accounting for one or more covariates. The record does not identify the covariates or provide a full model description. The reported statistic is called a median difference (net), so it should not be relabeled as the unadjusted mean difference.

In general, a confidence interval gives a range of values compatible with the data and the method’s assumptions at its stated confidence level. It communicates both the estimated contrast and uncertainty around it. A p-value summarizes how unusual data at least this incompatible with a specified null model would be if that model and the test assumptions held. A p-value is not the probability that the null hypothesis is true, nor is it a direct measure of clinical importance.

What does non-inferiority require?

In general, a non-inferiority analysis asks whether the data rule out a loss larger than a prespecified acceptable margin. The relevant decision depends on the direction of the contrast, the confidence interval, the margin, and the analysis plan. A result that is not statistically different from zero does not on its own demonstrate non-inferiority. The registry labels the sponsor’s analysis as non-inferiority or equivalence, but the margin, direction convention, and decision rule are not reported in the registry record. The numerical result alone therefore does not allow that criterion to be checked.

Equivalence is also distinct from failure to detect a difference. In general, equivalence requires evidence that the plausible contrast lies within prespecified bounds on both sides. Those bounds are not reported in the registry record. The posted p-value should not be read as proof that the groups are equivalent.

What is the role of the analysis population and missing observations?

The primary endpoint used the Per Protocol Set, defined in the record by exclusions from the Full Analysis Set for protocol violations assessed as making participants unsuitable for efficacy evaluation. The record also says on-treatment last observations within the phase were carried forward as final assessment values. This is a form of last-observation-carried-forward handling for the stated endpoint. The record excludes participants who withdrew before Week 2 and had only one Part III observation.

As a general statistical matter, carrying an earlier observation forward assumes that it is an appropriate substitute for the later unobserved score. If scores would have changed after the last observation, this approach may not represent that later course. The record does not report the number or reasons for missing observations, sensitivity analyses, or other missing-data methods for the primary outcome. The extent to which missingness could affect the comparison cannot therefore be assessed from these details alone.

Only the registry-described methods and posted results can be interpreted from this record. The original sample-size rationale, detailed analysis plan, model diagnostics, interim analyses, and full covariate specification are not reported in the registry record.

11. Confidence Intervals and Precision

The sponsor-reported estimate is a median difference (net) of 0.34, with a 95% confidence interval from -1.41 to 2.09. The interval includes zero and extends to values on either side of it. This describes uncertainty in the estimated contrast; it does not establish that the true contrast is zero. The sponsor p-value is 0.702.

The unadjusted re-calculation estimates a mean difference of -0.2 points, with an interval from -2.081 to 1.681 and p = 0.835. The interval also includes zero and includes contrasts in either direction. It is based on the posted group means and standard deviations, and should be read separately from the ANCOVA estimate because the estimands and methods differ.

In general, a confidence interval is a range of values that are reasonably compatible with the observed data under the analysis method. A narrower interval indicates greater precision for that contrast, while a wider interval indicates greater uncertainty. Precision is not the same as clinical importance: the interval must be considered alongside the endpoint’s meaning and any prespecified clinical or non-inferiority threshold. The threshold and non-inferiority margin are not reported in the registry record.

The available intervals do not justify interpreting a non-significant p-value as proof of no difference. Nor can the sponsor interval be assessed against a non-inferiority boundary without knowing that boundary. The participant counts in the primary analysis are 141 and 133, but the registry does not provide enough information about missing observations or the original analysis plan to determine how alternative assumptions would affect precision.

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 trial’s original design justification. For this continuous endpoint, the figures are participants per arm, not total events. 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 set at the stated fraction of the observed effect.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are design calculations, not estimates of the probability that the observed trial result is correct.

The rows for 100%, 75%, and 50% of the observed effect show how the planning figure changes as the target effect becomes smaller. A smaller effect is harder to distinguish from random variation, so the illustration requires more participants per arm. The plotted curve represents this planning relationship across effect sizes; it is not an observed outcome curve.

These figures are not observed power. The trial’s own original sample-size assumptions and justification are not reported in the registry record. The planning values are therefore useful for understanding how assumed effect size and desired power affect a hypothetical design, but they do not establish whether the trial was adequately powered for its prespecified non-inferiority question.

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 = -0.200; pooled standard deviation σ = 7.960.
2. n = 2 × (1.96 + 0.842)² × 7.960² / -0.200² = 24,867.4, rounded up to 24,868 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 <- -0.199999999999999                      # observed difference in means
sigma <- 7.96024386265529                     # 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(823836)
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 = 24,868 (80% power), 33,291 (90% power)
 75% of observed effect: n per arm = 44,209 (80% power), 59,183 (90% power)
 50% of observed effect: n per arm = 99,470 (80% power), 133,162 (90% power)
power.t.test: 24868.4 
Simulated power at n = 24,868 per arm: 0.802 (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’s sponsor-reported primary analysis used ANCOVA and gives a median difference (net) of 0.34, a 95% confidence interval from -1.41 to 2.09, and p = 0.702. It is identified in the record as a non-inferiority or equivalence analysis. The re-calculation instead compares the posted group means without adjustment and estimates an IR-minus-PR mean difference of -0.2, with an interval from -2.081 to 1.681 and p = 0.835.

These analyses are not identical: the reported statistic and method differ, and the registry does not provide the sponsor model’s covariates or full specification. The re-calculation is a check of the posted summaries, not a replacement for the sponsor’s analysis. The registry discrepancy indicator is false, so there is no flagged numerical discrepancy to resolve by preferring one result over the other.

The non-inferiority or equivalence label does not by itself establish that the criterion was met. The margin and decision rule are not reported in the registry record. The sponsor’s estimate and interval should be read as the registry’s reported inferential result, while the margin-dependent conclusion remains uncheckable from the recorded information.

15. Multiplicity, Missing Data and Analysis Populations

The primary analysis is identified as the mean change in Japanese UPDRS Part III score at the final assessment point in the non-inferiority verification phase. The registry also lists numerous secondary outcomes. The original protocol’s endpoint hierarchy, multiplicity-control method, and rules for interpreting multiple comparisons are not reported in the registry record. Without those details, secondary unadjusted p-values should not be treated as if they had been protected against the increased chance of false-positive findings that can arise when many outcomes are examined.

The primary analysis population was the Per Protocol Set. The record describes exclusions from the Full Analysis Set for protocol violations assessed as disqualifying participants from efficacy assessment. It also states that on-treatment last observations within the phase were carried forward as final assessment values. Participants who withdrew before Week 2 and had only one Part III observation were excluded from the primary analysis.

These details identify some analysis-population and missing-observation decisions, but they do not provide a full account of missing data. The numbers and reasons for withdrawals, the amount of missing endpoint information, and sensitivity analyses are not reported in the registry record. Nor is a parallel primary estimate from another analysis population reported in the registry record for this endpoint. As a general matter, results can depend on assumptions about observations that were not collected; the record does not allow the effect of alternative assumptions to be assessed.

The non-inferiority margin, original sample-size justification, detailed statistical analysis plan, interim analyses, and criteria governing any protocol deviations are not reported in the registry record. These omissions limit independent assessment of how the analysis decisions align with the planned question. They do not imply that such procedures were absent; their details are simply not reported in the registry record.

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: compression fracture (1.4%), cerebral infarction (1.3%), pneumonia (1.3%), post herpetic neuralgia (0.7%), appendicitis (0.7%).

The serious adverse event summaries report 16 affected participants among 156 at risk in the Ropinirole PR-Ropinirole PR group and 16 among 146 at risk in the Ropinirole IR-Ropinirole PR group. These are counts and denominators for the registry’s serious adverse event summaries; they are not the primary efficacy analysis counts. The record lists compression fracture at 1.4%, cerebral infarction at 1.3%, pneumonia at 1.3%, post herpetic neuralgia at 0.7%, appendicitis at 0.7%, and pyelonephritis at 0.7% among the top serious event terms.

The other adverse event summaries report 95 affected participants among 156 at risk in the PR group and 98 among 146 in the IR group. Death counts are not reported in the registry record. The event-term percentages are presented as recorded and are not assigned to a particular arm in the available details.

These summaries describe recorded events, not a causal comparison. Differences in counts can reflect group size, follow-up, event definitions, and other factors. The registry information does not provide enough detail to establish whether an event was caused by treatment or to make a complete comparative safety assessment. Adverse-event counts should therefore be read alongside their denominators and the registry’s reporting scope.

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

The primary results describe mean change in a motor examination score among participants in the Per Protocol Set, assessed at the final assessment point up to Week 24. The posted group means are -10.8 and -11.0, and the unadjusted re-calculated contrast is -0.2 points. The sponsor’s ANCOVA analysis reports a median difference (net) of 0.34. These are numerical summaries of this trial’s recorded endpoint, not general estimates for every person with Parkinson’s disease or every use of ropinirole.

The results do not establish that the regimens are identical. A non-significant test does not prove there is no difference, and an interval that includes zero still allows a range of possible contrasts. The registry labels the sponsor analysis as non-inferiority or equivalence, but the margin and decision rule needed to verify such a conclusion are not reported in the registry record. The available record therefore does not permit an independent determination that a non-inferiority or equivalence criterion was met.

The endpoint is a scored assessment of motor examination, not a direct measure of every symptom, daily activity, quality of life, or long-term outcome. Secondary UPDRS measures provide additional domains, but they have different definitions and are subject to multiplicity concerns. The safety summaries report adverse event counts and selected event terms; they do not, by themselves, establish causation or fully characterize comparative safety.

In general, interpreting clinical trial results requires attention to the population analyzed, outcome definition, uncertainty, analysis plan, and clinical thresholds. Here, the primary analysis used a per-protocol population and included a stated carry-forward approach. Details of missingness, the original sample-size rationale, and the full statistical plan are not reported in the registry record. Those limits should temper conclusions drawn from the numerical results.

18. Why This Trial Matters Statistically

This trial is statistically informative because it presents a randomized, double-blind, parallel-group comparison and a continuous primary outcome with group means, standard deviations, and participant counts. Those summaries make it possible to describe the observed contrast and to calculate an unadjusted comparison from the posted statistics. The registry also reports a sponsor ANCOVA analysis, allowing readers to distinguish that reported analysis from the simpler re-calculation.

The non-inferiority framing highlights an important interpretive distinction. A finding that does not demonstrate a difference is not automatically evidence of non-inferiority or equivalence. Those conclusions depend on prespecified margins and decision rules, which are not reported in the registry record. The example illustrates why the reported estimate and p-value should be considered together with the analysis objective and its threshold.

The trial also shows why analysis populations and missing-data choices matter. The primary endpoint uses a Per Protocol Set, includes a stated last-observation-carried-forward procedure, and excludes participants with only one early Part III observation after withdrawal. Such choices define which participants and measurements contribute to the result. The registry record does not include enough detail to assess sensitivity to other population or missing-data assumptions.

Finally, the large collection of listed outcomes makes multiplicity relevant. Secondary findings can help describe the broader pattern, but unadjusted results deserve less confirmatory weight when many measures are considered. Overall, the statistical value of the record lies in the transparency of its posted summaries and in the questions the missing protocol and analysis details leave open.

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 primary comparison is based on the Per Protocol Set rather than all enrolled participants. The record describes exclusions for protocol violations and the use of last on-treatment observations carried forward as final assessment values. It also excludes participants who withdrew before Week 2 with only one Part III observation. The number of participants affected by each decision, reasons for withdrawal, and sensitivity of the results to alternative missing-data assumptions are not reported in the registry record.

The sponsor reports an ANCOVA result, but the covariates and full model specification are not reported in the registry record. The sponsor’s non-inferiority or equivalence label cannot be checked against a margin because that margin and the decision rule are not reported. The original sample-size rationale is also not reported, so the planning illustrations based on the observed effect should not be mistaken for the trial’s design calculations.

The primary outcome concerns Japanese UPDRS Part III motor examination scores at a final assessment point up to Week 24. The record does not report a clinical importance threshold for the score change. The available summaries do not establish how results would vary in other analysis populations, at other follow-up periods, or in groups defined by participant characteristics.

The trial lists numerous secondary outcomes, while no multiplicity adjustment or endpoint hierarchy is reported in the registry record. Safety summaries give affected-participant counts and selected serious event terms, but death counts are not reported and the details do not establish causality. These limitations constrain interpretation of both efficacy and safety; they do not imply that unreported procedures or information were absent from the trial.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease — NCT00823836.
• Registry record last updated 2017-01-18; status last verified 2016-11.
• Results first posted 2011-10-07.
• 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 completed randomized, double-blind, parallel-group Phase 3 trial compared ropinirole PR/XR with ropinirole IR as adjunctive therapy to L-dopa in advanced Parkinson’s disease. Enrollment was 302. The primary outcome was mean change in Japanese UPDRS Part III total score from Week 0 to the final assessment point, up to Week 24, in the Per Protocol Set.

Primary group means were -10.8 and -11.0. The sponsor-reported ANCOVA result was a median difference (net) of 0.34, with a 95% confidence interval from -1.41 to 2.09 and p = 0.702. The unadjusted re-calculation estimated a mean difference of -0.2, with an interval from -2.081 to 1.681 and p = 0.835. The registry labels the sponsor analysis as non-inferiority or equivalence, but the margin and decision rule are not reported in the registry record.

The record also describes secondary outcomes, adverse event summaries, and a last-observation-carried-forward approach for the primary phase assessment. Important details, including the original sample-size justification, multiplicity plan, and full missing-data and model specifications, are not reported in the registry record.