Pramipexole ER vs. Placebo in Fibromyalgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pramipexole ER vs. Placebo in Fibromyalgia (NCT00689052), a randomized phase 2 study. The primary outcome is The Change in the Weekly Mean of the 24-hour Average Pain Score From a Daily Diary as Measured by the 11-point Likert Pain Scale.

2. Clinical Question

The question is about change in reported pain intensity over time, not simply the pain score at a single assessment. The record defines the scale as ranging from 0 for no pain to 10 for worst possible pain. Although the primary endpoint is identified, its result is not reported in the registry record. As a result, the stated study question can be described, but its answer cannot be determined from the posted results.

3. Trial Design

This was a randomized, parallel-group phase 2 study comparing pramipexole extended-release with placebo in patients with fibromyalgia. The registry lists quadruple masking. It does not specify which study roles were masked or provide further details about allocation procedures, so those aspects cannot be described more precisely.

The pramipexole arm used tablets in a dose range from 0.75 mg to 4.5 mg, taken orally once daily in the evening. The placebo arm used placebo tablets on the same stated daily evening schedule. The official title describes dose titration, a 16-week maintenance phase, and a subsequent 24-week open-label extension. The primary endpoint timeframe is listed as baseline and Week 29. The record does not explain how that endpoint timing relates to the maintenance and extension phases described in the title.

Enrollment is listed as 61. The study start is recorded as 2008-07, and primary completion as 2008-11. The status is terminated. The registry record does not state why the study was terminated, whether the planned study activities were completed, or how termination affected follow-up or reporting. Those details should not be inferred from the status alone.

The primary objective was to assess efficacy and safety compared with placebo. The open-label phase was intended to assess the safety profile and effect of pramipexole extended-release over a 24-week period. The record lists a range of secondary outcomes, including global improvement, physical functioning, pain improvement thresholds, fibromyalgia impact, anxiety and depression, health status, quality of life, and fatigue. Their presence indicates a broad outcome program, but the registry record does not report analyses for these outcomes.

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: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Treated Set, All patients randomized and received treatment

6. Primary Endpoint

The registry lists the primary outcome as The Change in the Weekly Mean of the 24-hour Average Pain Score From a Daily Diary as Measured by the 11-point Likert Pain Scale, measured over Baseline and Week 29.

The primary endpoint is the change in the weekly mean of the 24-hour average pain score, recorded in a daily diary using the 11-point Likert Pain Scale. The record describes the scale as measuring pain intensity from 0, no pain, to 10, worst possible pain. The assessment timeframe is baseline and Week 29, and the stated population is the Full Analysis Set.

Change from baseline expresses how a participant’s measured score at a later assessment differs from that participant’s starting score. The weekly mean of daily 24-hour average scores is intended to represent pain across diary assessments rather than rely on a single rating. In general, repeated diary measurements can capture variation over time, while averaging can make the endpoint less dependent on one day’s report. These are general features of such measures; the registry record does not describe the diary completion rules or the calculation details beyond the endpoint wording.

Pain intensity is relevant to the stated objective because the study concerns fibromyalgia and the endpoint directly measures pain reported by patients. The outcome is a measure of symptom intensity, not a measure of every aspect of health or functioning. The record identifies the measure and time point but does not report the observed changes, between-group contrast, uncertainty interval, or statistical test. Therefore, the endpoint’s clinical meaning can be explained, but the posted results do not show the estimated treatment comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods used for the primary endpoint are not reported in the registry record. The record names the outcome, timeframe, and analysis population, but it does not state the model, test, adjustment variables, handling of repeated measurements, or method for estimating uncertainty. It also does not provide an observed primary outcome result. The explanations below are general descriptions of how these methods and concepts are commonly interpreted; they are not claims about the analysis conducted in this trial.

What does the primary endpoint represent?

The outcome is a change from baseline in the weekly mean of the 24-hour average pain score. A change score compares a participant’s later measurement with their baseline measurement. The treatment comparison would ordinarily summarize how these changes differed between the randomized groups. A group-level comparison is distinct from asking whether the average score changed within either group: change over time in both groups could reflect many influences, and the randomized between-group comparison is the relevant contrast for the stated objective.

The endpoint uses daily diary information to form a weekly mean. In general, diaries can collect repeated reports closer to the time being assessed and can show variation across days. Averaging repeated scores can reduce the influence of an unusually high or low rating, though it also depends on how missing diary entries are handled. The registry record does not describe diary completion requirements, minimum numbers of daily entries, or rules for deriving the weekly mean when entries are absent.

Why do estimates and uncertainty matter?

A statistical estimate describes the size and direction of a comparison in the observed data. A confidence interval is a general way to express uncertainty around an estimate: it indicates a range of values compatible with the data and the method’s assumptions. A narrow interval indicates greater precision than a wide interval, but the interval’s interpretation depends on the analysis and its assumptions. Neither an estimate nor a confidence interval is reported for the primary endpoint in the registry record.

A p-value, when reported, describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the statistical model. It is not the probability that the null hypothesis is true, nor does it measure the magnitude or clinical importance of an effect. No primary endpoint p-value is reported. The absence of a posted p-value cannot be read as a nonsignificant result; there is no reported test result to interpret.

What can randomization and masking contribute?

In general, random assignment aims to balance prognostic factors between groups and supports interpretation of a between-group contrast. Chance imbalances can still occur, especially in a study with limited enrollment. Randomization does not ensure complete follow-up, correct outcome measurement, or unbiased analysis if data are missing or analytic choices are problematic. The record states that the study was randomized and quadruple-masked but does not describe allocation concealment or which roles were masked. Those details are not reported in the registry record.

Masking can, in general, reduce the influence of knowledge about assignment on participant reports, care, or outcome assessment. Its value depends on which people are masked and whether masking is maintained. Since the record does not identify the masked roles or describe assessment procedures, it is not possible to assess those details for this study.

What is known about sample-size planning?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such an illustration is not evidence that the trial was designed around those assumptions, and it is not observed power. The record does not report the trial’s own sample-size justification or statistical plan. No observed primary effect is posted, so the planning assumptions cannot be used to establish what the trial found.

In general, sample-size planning estimates how much information may be needed to detect a specified effect under stated assumptions. It does not guarantee that a future study will obtain a particular result, and it cannot compensate for an unclear endpoint definition, missing observations, or inadequate reporting. A planning illustration based on an observed effect is particularly dependent on the quality and availability of that effect estimate. It should be interpreted as a scenario, not as a result from the trial.

Why can variation beyond a simple model matter?

General statistical models make assumptions about how outcomes vary and how observations relate to one another. If outcome variation is greater than a model assumes, uncertainty estimates can be too optimistic unless the analysis accounts for that extra variation. Repeated diary measurements may also be correlated within a participant, because measurements from the same person are not necessarily independent. Appropriate analysis often needs to account for the outcome’s structure and repeated observations. The registry record does not report whether or how these issues were addressed.

The central methodological conclusion is therefore limited: the record identifies the design and primary endpoint but does not give enough information to reconstruct or evaluate the primary statistical analysis. Any specific account of the model, standard errors, assumptions, or treatment effect would go beyond what is reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary pain endpoint and a range of secondary measures. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if all tests are interpreted without accounting for multiplicity. General approaches include prespecifying a primary outcome, using a hierarchy of tests, or adjusting inference across a defined family of comparisons. The registry record does not report whether any such strategy was used, how the outcomes were prioritized beyond identifying the primary endpoint, or which comparisons were planned.

The record lists zero analyses. It therefore does not provide results across which to assess consistency, selective reporting, or multiplicity adjustment. The statistical analysis plan, interim analyses, and any prespecified rules for testing are not reported in the registry record. No assumptions about them should be made from the outcome list alone.

The primary population is described as the Full Analysis Set, defined as randomized and treated patients with a baseline and at least one post-baseline measurement. The record does not give the number in that population, its distribution by arm, or the number contributing to the Week 29 endpoint. It also does not state how missing baseline, diary, or follow-up data were handled, whether participants were analyzed according to randomized assignment, or whether sensitivity analyses were conducted.

In general, missing outcome data can affect an estimate when the reasons for missingness are related to participants’ outcomes or differ between groups. Methods such as imputation or likelihood-based analyses rely on assumptions, and sensitivity analyses can help explore how conclusions depend on those assumptions. These are general considerations, not descriptions of methods used in this trial. Because the registry does not report missing-data procedures or endpoint results, the extent and potential impact of missingness cannot be assessed.

11. 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: iron deficiency anaemia (3.2%).

The registry lists serious adverse events for the placebo group as 1 event among 31 at risk, and for the pramipexole group as 0 among 30 at risk. It lists other adverse events as 10 among 31 for placebo and 18 among 30 for pramipexole. These are recorded counts with their stated at-risk denominators. They are not, by themselves, estimates of a treatment effect, and the registry does not report statistical comparisons or uncertainty intervals for them.

The record lists Iron deficiency anaemia at 3.2% among the top serious adverse-event terms. That entry does not identify an arm, so it should not be assigned to either group. The record gives no death counts; the death fields are null. A null entry means the record does not report a count there, not that no deaths occurred.

In general, adverse-event counts are interpreted in light of definitions, observation periods, severity, exposure, and completeness of reporting. Those details are not all reported in the registry record. The counts should therefore be read as the posted safety information, not as a comprehensive comparison of risk or proof of safety or harm.

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

The registry record establishes that a randomized, parallel-group study was registered to compare pramipexole extended-release with placebo for fibromyalgia. It identifies a primary pain endpoint, its scale, the assessment timeframe, and the Full Analysis Set definition. It also reports some adverse-event counts and lists secondary outcomes. These registry entries describe the study’s intended question and the safety information posted in the record.

The record does not report the primary endpoint analysis. It gives no arm-specific change in pain, between-group estimate, confidence interval, or p-value. As a result, it does not show whether the groups differed in pain change, the size or direction of any difference, or how precisely a comparison was estimated. Missing results are not evidence of no effect, and they do not demonstrate equivalence between treatments.

The safety counts are also limited. They describe recorded events among the stated at-risk groups, but the record does not provide statistical comparisons or uncertainty measures. The serious-event term listed at 3.2% is not assigned to a study arm. The death fields are null, which does not establish that there were no deaths. A complete safety interpretation would require further information about event definitions, timing, follow-up, and reporting.

The status is terminated, but the reason and consequences for completion or analysis are not reported. The record also does not explain whether the Week 29 endpoint was assessed as planned in relation to the maintenance and open-label phases described in the title. These reporting gaps limit interpretation of both the conduct and the results.

Accordingly, the posted record is informative about the study design and selected safety counts, but it does not support a conclusion about the primary efficacy comparison. It cannot establish that pramipexole improved pain, failed to improve pain, or had the same effect as placebo. It also cannot establish the absence of safety concerns. The distinction is between a trial being registered with a stated objective and a trial having results reported in sufficient detail to answer that objective.

13. Why This Trial Matters Statistically

This trial illustrates a basic principle of clinical-trial interpretation: a clearly stated research question is not the same as a reported answer. The registry describes randomization, masking, the treatment and comparator, and a patient-reported pain endpoint. Those details help identify what was intended to be compared. Without the primary outcome estimates and their uncertainty, however, the statistical question remains unanswered by the posted results.

The record also illustrates why endpoint definitions and analysis populations matter. The primary outcome is a change in weekly mean pain scores, and the stated population requires treatment and outcome measurements after baseline. Knowing those definitions helps readers understand what a future or complete report should analyze. The absence of the final population size, missing-data methods, and endpoint results prevents assessment of how completely that analysis represents the randomized groups.

The listing of 13 outcome measures makes multiplicity relevant as a general concern, while the absence of reported analyses prevents evaluation of how outcomes were tested or prioritized. A statistical plan would clarify which comparisons were prespecified and how uncertainty was handled. The record does not report such a plan, so results should not be reconstructed from outcome descriptions or safety entries.

Finally, the study’s terminated status and the mismatch between the Week 29 endpoint timeframe and the phases described in the title are details that merit cautious reading, not speculation. The registry does not explain the reason for termination or the relationship between the endpoint timing and study phases. Separating what the record states from what it leaves unreported is essential: design information can frame a study, but it cannot substitute for outcome estimates.

14. Limitations

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

Several trial-specific reporting gaps constrain interpretation. The primary outcome is named, but its results are not reported in the registry record. There are no posted group-specific changes, treatment contrast, uncertainty interval, or p-value. The record lists zero analyses, so the primary question and secondary outcome descriptions cannot be linked to reported statistical findings.

The outcome timeframe also warrants careful description. The primary endpoint is specified at baseline and Week 29, while the official title describes a 16-week maintenance phase followed by a 24-week open-label extension. The registry record does not explain the relationship between the endpoint timing and those study phases. This should be treated as an unresolved reporting detail, not reconciled by assumption.

The study is marked terminated, but the reason, timing in relation to planned activities, and effect on follow-up or analysis are not reported. Enrollment is listed as 61, but the final analysis population and endpoint-specific availability are not given. The record defines the Full Analysis Set but does not state how many participants met its criteria or how missing outcomes were handled.

Further limitations include the absence of a reported statistical analysis plan, sample-size justification, allocation-concealment details, and identification of the roles covered by quadruple masking. The record does not describe diary completion rules or the statistical model for repeated pain measurements. Adverse-event counts are posted without comparison estimates or uncertainty, and the listed serious-event term is not attributed to an arm. These omissions limit conclusions about efficacy, precision, completeness, and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pramipexole ER vs. Placebo in Fibromyalgia — NCT00689052.
• Registry record last updated 2014-06-09; status last verified 2014-05.
• Results first posted 2009-11-25.
• 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.

18. Record Summary

The registry record describes a randomized, parallel-group phase 2 study of pramipexole extended-release versus placebo in fibromyalgia. It lists quadruple masking, enrollment of 61, and a terminated status. The treatment was taken once daily in the evening, with pramipexole titrated from 0.75 mg to 4.5 mg. The title describes a 16-week maintenance phase and a 24-week open-label extension.

The primary outcome is change in weekly mean 24-hour average pain score on an 11-point Likert Pain Scale, assessed at baseline and Week 29 in the Full Analysis Set. The registry lists 13 outcome measures and zero analyses. It reports adverse-event counts, but no primary outcome estimate or statistical comparison. The reason for termination, missing-data procedures, and statistical analysis plan are not reported in the registry record.