REQUIP RLS Post Marketing Surveillance: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for REQUIP RLS Post Marketing Surveillance (NCT01327339), a registered phase not stated study. The primary outcome is Number of Participants With Any Adverse Event.

2. Clinical Question

3. Trial Design

NCT01327339 is titled REQUIP RLS Post Marketing Surveillance. The official title describes an open-label, multicentre, observational, post-marketing surveillance study intended to monitor the safety of REQUIP (ropinirole) administered to Korean patients with restless legs syndrome according to prescribing information. Its stated purpose also refers to monitoring efficacy, but an efficacy outcome result is not reported in the registry record.

The registry reports enrollment of 755. The study start date is 2006-04-01, the primary completion date is 2009-11-30, and the status is completed. The intervention is ropinirole, and the reported group is titled Requip 0.25 mg, 1 mg, 2 mg. The description says that male and female participants considered appropriate for a prescription under the prescribing information were included. It does not give further eligibility criteria, recruitment procedures, or the number or locations of participating centres.

This is an observational surveillance record, not a randomized controlled trial. Allocation is not stated, and no control group is reported. Consequently, the reported safety counts describe participants in the treated group; they do not estimate a comparative difference between ropinirole and another treatment or a no-treatment group. The registry does not report how the listed doses were selected or distributed, nor does it describe changes in dose or treatment duration.

The safety population is defined as participants who had received the investigational drug at least once and completed all safety assessments. The registry gives 747 as the at-risk denominator for the reported serious and other adverse-event counts. It does not explain how this population relates to total enrollment, or give details about missing safety assessments or participants excluded from that population.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants who had been administered the investigational drug at least once and had completed all safety assessments.

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 Number of Participants With Any Adverse Event, measured over one month.

The primary endpoint is the number of participants with any adverse event during the stated timeframe of one month. It is a count of participants, rather than a measure of event severity, duration, or frequency of repeated events. The registry defines an adverse event as any untoward medical occurrence temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. This definition does not require the event to have been judged caused by ropinirole.

Counting participants with any adverse event is a way to describe the occurrence of reported safety events during a specified period. For an individual participant, the endpoint indicates whether an event was recorded, rather than how many separate events occurred. It can therefore offer a concise summary of how many participants experienced at least one event, while leaving details such as event type, seriousness, timing, and attribution to other measures.

The one-month timeframe is part of the endpoint definition and limits what the endpoint is intended to capture. It should not be read as a summary of safety over an unspecified longer period. The primary endpoint result is not reported in the registry record. Although safety counts are posted for serious and other adverse events, they do not establish the number of participants with any adverse event under the primary endpoint definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The reported safety outcomes are counts of participants with events. A participant count answers how many people in the stated population experienced an event meeting the outcome definition. It is not necessarily a count of all event episodes: a participant with repeated events may still be counted once for an outcome defined as the number of participants with an event. Event-level frequency and participant-level frequency are different summaries, and the registry record does not provide enough detail to reconstruct event episodes from the posted participant counts.

For this study, the primary outcome is the number of participants with any adverse event during one month. The definition includes an untoward medical occurrence temporally associated with use of a medicinal product, regardless of whether it is considered related to that product. Thus, occurrence and causal attribution are separate concepts. Recording an event under this definition does not itself establish that ropinirole caused it.

How should counts and denominators be read?

A count is most interpretable alongside the population from which it was obtained. The registry reports 3 participants with a serious adverse event and 44 with other adverse events, each against an at-risk denominator of 747. Those values are descriptive summaries for the recorded safety population. The at-risk denominator is not the same as an outcome result for the primary endpoint, and it does not answer whether participants had any adverse event over the specified timeframe.

In general, a proportion is formed by relating an event count to the number of participants at risk. The registry record does not post a proportion for these counts in the registry record for this analysis, so no additional proportion is calculated. The serious-event term values are reported as 0.1% and are quoted as recorded. The registry does not supply the event-level detail needed to determine whether terms overlap within participants or how they were categorized.

What would uncertainty estimates add?

In general, a confidence interval describes a range of parameter values compatible with the observed data under a chosen statistical model and confidence procedure. It can indicate how imprecise an estimate may be, but it does not address every source of uncertainty. In an observational safety record, uncertainty may also arise from incomplete reporting, outcome ascertainment, selection into the analyzed population, and the absence of a comparison group. No confidence intervals for the posted safety counts are reported in the registry record.

A p-value, in general, is a measure of how unusual data would be under a specified null hypothesis and statistical model. It is not a measure of the probability that a treatment works or that an observed event was caused by treatment. No p-value or hypothesis test for the reported safety counts is reported in the registry record. Since there is no control group, the counts do not support a treatment-versus-control test on the information reported.

Why does the study design matter to statistical interpretation?

Random allocation can make treatment groups more comparable in expectation, but this study is described as observational and no allocation method is stated. The record lists one ropinirole group and does not report a like-for-like control group. Differences between groups, treatment effects, and comparative risks therefore cannot be estimated from the posted counts. Even a precise count in the treated group would remain a description of that group rather than a controlled estimate of what treatment changed.

Open-label means the study is described as not blinded. The registry does not report details of adverse-event ascertainment, so the extent to which participants’ or assessors’ knowledge influenced reporting cannot be evaluated. This is a general consideration for open-label safety reporting, not a claim that reporting was biased in this study.

What is not available about the analysis?

The record lists one analysis and three outcome measures, but it does not report the statistical procedures used for the safety results. Specific details such as a prespecified analysis plan, adjustment methods, interim analyses, or a sample-size justification are not reported in the registry record. The enrollment figure alone does not show what level of precision or ability to detect an event frequency was intended.

General sample-size planning depends on design assumptions and a target effect or precision. A planning illustration is not observed evidence and does not establish the power of a completed study. No numeric planning result is included in the record used for this interpretation. The statistical methods and analysis choices behind the posted counts therefore cannot be independently assessed from the registry information available.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Requip 0.25 mg, 1 mg, 2 mg")
n      <- c(747)
events <- c(44)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Requip 0.25 mg, 1 mg, 2 mg  747  44  5.9  4.3  7.8  4.4  7.8  4.4  7.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary outcome of participants with any adverse event and secondary outcomes for participants with any serious adverse event and participants with indicated unexpected adverse events. It lists one analysis. The statistical plan for these outcomes, including any prespecified testing sequence, multiplicity adjustment, or distinction between confirmatory and exploratory analyses, is not reported in the registry record. Because the primary endpoint result is not reported, there is no basis for interpreting a family of outcome tests or their error-rate control.

Missing-data handling is also not reported in the registry record. The safety population is defined as participants who received the investigational drug at least once and completed all safety assessments. The record does not specify how incomplete assessments were handled, whether participants with partial follow-up contributed to any outcomes, or whether missingness was assessed by reason or participant characteristics. It also does not state whether any imputation or sensitivity analysis was used.

The enrollment figure is 755, while the adverse-event denominator is 747. The reason for this difference is not reported in the registry record. It should not be assumed that the participants outside the safety denominator had no events, nor can their event status be inferred from the reported counts. The available record gives no separate disposition accounting that would clarify their status.

The population definition and missing-data details matter because a count among participants with completed safety assessments may differ from a count among all enrolled participants. Without fuller reporting, the extent to which incomplete follow-up affects the safety summaries cannot be determined. No participant-level data are reported to assess that issue independently.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: melena (0.1%), appendicitis (0.1%), abdominal pain (0.1%), dizziness (0.1%).

The registry reports 3 participants with a serious adverse event among 747 at risk, and 44 participants with other adverse events among 747 at risk. These are participant counts, not a comparison between treatment groups. The reported serious-event terms are Melena, Appendicitis, Abdominal Pain, and Dizziness, each listed as 0.1%. The registry record does not provide event narratives, timing, severity details beyond the serious-event category, or judgments about relationship to ropinirole.

The two counts should be read as the reported categories, not added together to infer the number with any adverse event. The registry does not state whether the categories overlap, and the primary endpoint result for any adverse event is not reported in the registry record. The number of deaths is also not reported in the registry record.

These data are descriptive observations from a post-marketing surveillance study. They do not establish a cause-and-effect relationship, and no control group is reported for comparison. The denominator represents the stated at-risk safety population; the record does not explain why it differs from the enrollment figure of 755. These reporting limits constrain conclusions about the completeness and comparability of the safety counts.

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

The record documents a post-marketing safety study of ropinirole in Korean patients with restless legs syndrome and posts counts for serious and other adverse events. The counts describe events recorded among participants in the stated safety population. They are useful as a registry-level account of what was reported, but they do not by themselves estimate a comparative treatment effect or establish that an event was caused by ropinirole.

The primary endpoint is the number of participants with any adverse event during one month. Its result is not reported in the registry record. The serious and other adverse-event counts cannot be substituted for that missing endpoint, and the record does not clarify overlap between those categories. The listed serious-event terms and their reported values provide some detail, but do not give a complete account of event timing, individual histories, or attribution.

This study has no reported control group and is observational rather than randomized. Without a comparator, the posted data cannot indicate how the event counts differ from another treatment or from an untreated course. Open-label surveillance can describe events observed during use, but the record does not report enough about ascertainment to assess how events were identified or classified.

The findings also do not establish the absence of events beyond those reported. The registry does not provide the primary any-adverse-event result, confidence intervals, detailed missing-data handling, or a statistical analysis plan. The enrollment count and safety denominator differ, and the reason is not reported. The posted counts should therefore be understood as summaries for the stated safety population, not as a complete accounting of all enrolled participants.

In general, descriptive safety counts can contribute to monitoring and signal identification, while causal conclusions require an appropriate design and sufficiently detailed analysis. This record supports a cautious description of the reported safety observations; it does not support broader conclusions about comparative safety, efficacy, or causation.

14. Why This Trial Matters Statistically

Post-marketing surveillance addresses a different statistical question from a randomized efficacy comparison. It can record safety observations during routine use in a population considered appropriate for a prescription under the prescribing information. This study’s stated aim was to monitor safety and efficacy of ropinirole in Korean patients with restless legs syndrome, and its registry description identifies it as open-label, multicentre, and observational.

Statistically, the distinction between a count and a comparative estimate is important. The registry posts counts of participants with serious and other adverse events, but reports no control group. Those counts describe the observed treated group; they do not quantify a difference attributable to treatment. The primary any-adverse-event endpoint is also not reported, leaving the central stated safety measure unavailable in the registry record.

The population denominator is another important part of interpretation. Enrollment is reported as 755, while the safety counts use 747 as the at-risk denominator. The safety population requires completion of all safety assessments, but the record does not explain the difference between enrollment and the reported denominator. Transparent accounting of who contributes to each outcome helps readers judge how broadly a count applies.

The record also illustrates why event definitions and attribution should be kept distinct. An adverse event is defined by its temporal association with medicinal-product use, whether or not it is considered related to that product. Consequently, an event count is not itself a causal assessment. The listed serious-event terms add descriptive information, but the registry does not provide narratives or relatedness judgments.

For clinical researchers and biostatisticians, these features make this record useful as an example of the limits of interpreting surveillance counts. Clear denominators, complete outcome reporting, event-level detail, and an explicit analysis plan would support a more complete assessment. Where those details are absent, the sound statistical reading is descriptive and bounded by what the registry reports.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint result—the number of participants with any adverse event during one month—is not reported in the registry record. The posted counts for serious and other adverse events do not fill that gap, and the relationship between those categories is not described. The record therefore does not allow a complete interpretation of its stated primary safety measure.

No comparator is reported, and the study is observational and open-label. The allocation method is not stated. As a result, the safety counts cannot be compared with a control group, and causal attribution cannot be established from the reported data. The record also does not describe how adverse events were collected, verified, coded, or assessed for relationship to treatment.

Enrollment is 755, but the adverse-event denominators are 747. The reasons for this difference and the disposition of participants not included in the safety denominator are not reported in the registry record. Although the safety population is defined by treatment exposure and completion of safety assessments, the handling of incomplete assessments and missing outcomes is not stated.

The reported group title includes Requip 0.25 mg, 1 mg, and 2 mg, but the record does not explain dose selection, participant distribution across doses, or any dose changes. It does not provide event-level narratives, detailed follow-up beyond the endpoint’s one-month timeframe, or the number of deaths. The listed serious-event terms and values do not resolve these omissions.

Finally, the statistical analysis plan, sample-size justification, interim analyses, and methods for uncertainty estimation are not reported in the registry record. No confidence intervals for the safety counts are available. These limits mean the posted information supports a restricted descriptive reading, not a full assessment of precision, completeness, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: REQUIP RLS Post Marketing Surveillance — NCT01327339.
• Registry record last updated 2017-09-12; status last verified 2017-08.
• Results first posted 2011-04-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01327339 is a completed, open-label, multicentre, observational post-marketing surveillance study of ropinirole (REQUIP) in Korean patients with restless legs syndrome. The registry reports enrollment of 755, a start date of 2006-04-01, and a primary completion date of 2009-11-30. The stated purpose was to monitor safety and efficacy during use according to prescribing information.

The primary endpoint is the number of participants with any adverse event during one month, but its result is not reported in the registry record. For the reported safety population, the registry lists 3 participants with a serious adverse event and 44 with other adverse events, each using an at-risk denominator of 747. The listed serious-event terms are Melena, Appendicitis, Abdominal Pain, and Dizziness, each reported as 0.1%.

No control group is reported. The record does not explain the difference between enrollment and the safety denominator, provide the primary endpoint result, or report detailed analysis and missing-data methods. The counts are therefore descriptive and should not be interpreted as comparative or causal estimates.