This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Non-motor Symptoms (Depressive Symptoms) of Parkinson's Disease and Their Course Under Pramipexole Treatment (NCT00651183), a registered phase not stated study. The primary outcome is Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I (Mentation, Behaviour and Mood).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00651183 |
| Phase | Phase not stated |
| Condition | Parkinson Disease |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 286 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
People diagnosed with Parkinson disease, including patients described as having early or advanced disease. The brief summary describes a planned investigation of 250 patients, while the registry enrollment is 286. The primary outcome analysis was restricted to members of the full analysis set who had an UPDRS Part I evaluation at visit 3; the size of that analysis population is not reported in the registry record.
Intervention
Pramipexole immediate release. The brief summary describes oral treatment beginning at 0.375 mg/day, on a three-times-daily schedule, with possible weekly upward titration to a maximum total daily dose of 4,5 mg, as described there. Those are treatment instructions in the study summary, not evidence that every participant reached the same dose.
Comparator
The registry record does not identify a separate untreated or active control group. Early and advanced Parkinson disease are the groups used in the adverse-event record, not a like-for-like control comparison. Allocation is not stated, and the record characterizes the study as not a randomized comparison.
Primary question
The primary outcome concerns change from baseline to final visit, visit 3, in UPDRS Part I, which rates mentation, behaviour and mood. The registry description treats a decrease in the score as improvement. The study summary also says it would investigate depressive symptoms using HADS-D and whether changes in depressive symptoms were linked to motor-function changes on UPDRS Part III. Outcome values and analyses for these questions are not reported in the registry record.
3. Trial Design
The registry describes a completed study of pramipexole immediate release in people with Parkinson disease. It identifies the study as a PMS study and states that the investigation concerned depressive symptoms in patients with early and advanced disease. The sponsor is Boehringer Ingelheim. The primary completion date is 2008-04.
The brief summary describes a planned investigation of 250 patients by 80 specialists, neurologists or neurologists/psychiatrists, across Austria. The registry enrollment is 286. These figures describe different aspects of the record: the planned number in the summary and the recorded enrollment. The record does not explain the difference, and it should not be interpreted as the size of the primary outcome analysis population.
The described treatment was oral pramipexole, starting at 0.375 mg/day with a three-times-daily schedule and possible weekly titration to a maximum total daily dose of 4,5 mg. The record does not report the doses actually taken by participants. Allocation is not stated, and the record explicitly cautions that this is not a randomized comparison and that the groups are not a like-for-like control comparison. Early and advanced disease categories therefore should not be read as randomized treatment arms.
The primary outcome was change from baseline in UPDRS Part I by final visit, visit 3. Its analysis population was described as members of the full analysis set with an evaluation at visit 3. The study summary also names HADS-D and UPDRS Part III in its objectives. Detailed treatment duration, protocol deviations, and further design details 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.
Overall Study
| Stage | Early (PD) | Advanced PD |
|---|---|---|
| STARTED | 189 | 97 |
| COMPLETED | 169 | 87 |
| NOT COMPLETED | 20 | 10 |
Reasons for not completing this period:
| Reason | Early (PD) | Advanced PD |
|---|---|---|
| Lack of Efficacy | 1 | 0 |
| Efficacy insufficient + patients wish | 0 | 1 |
| Tolerability insufficient | 5 | 2 |
| Tolerability insufficient +Patients wish | 0 | 1 |
| Withdrawal by Subject | 6 | 3 |
| Lost to Follow-up | 3 | 1 |
| Other reasons | 4 | 2 |
| missing | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Only those patients of the full analysis set (FAS) with an evaluation of UPDRS Part I at visit 3 were included in this analysis
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: Safety set (SAF)
| Characteristic | Unit | Early PD | Advanced PD | Total |
|---|---|---|---|---|
| Participants analysed | 189 | 97 | 286 | |
| Age, Continuous | years | 69.1 (SD 9.44) | 73.8 (SD 6.97) | 70.6 (SD 8.96) |
| Sex/Gender, Customized: Female | participants | 80 | 35 | 115 |
| Sex/Gender, Customized: Male | participants | 108 | 61 | 169 |
| Sex/Gender, Customized: missing | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I (Mentation, Behaviour and Mood), measured over Baseline and Final (visit 3) - Change from baseline (i.e. decrease of score).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | Points on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change from baseline to final visit, visit 3, in UPDRS Part I, covering mentation, behaviour and mood during the past week. The registry describes four items scored from 0, normal, to 4, severe, and a total score from 0, best, to 16, worst. It states that a reduction in the total score over time is interpreted as improvement. The outcome is reported in points on a scale, with the median as the summary measure and the inter-quartile range as its dispersion.
As a general measurement principle, a structured scale turns observations about symptoms into a score that can be compared across assessment times. A change score focuses on how the recorded score differs from baseline, rather than only describing the final score. The direction of that change matters: for this endpoint, a lower score is the direction interpreted as improvement.
The endpoint is relevant to the stated study question because it captures the mentation, behaviour and mood domain of Parkinson disease symptoms. However, it is not described as a depression-specific diagnostic measure. HADS-D is also named in the brief study summary, but its result values are not reported in the registry record. The registry likewise does not report the observed median change, its inter-quartile range, or the number included in this endpoint analysis. The scale definition explains what a score means; it does not establish what change occurred in this study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies the primary outcome but does not report its observed value. It therefore does not establish the size or direction of the median change in UPDRS Part I, nor how variable the individual changes were. Although the outcome description says that a reduction is interpreted as improvement, the record does not give a result that can be compared with that direction. HADS-D and UPDRS Part III results are also not reported in the registry record.
The primary outcome is summarized using a median and an inter-quartile range. In general, the median describes the middle of the observed distribution, while the inter-quartile range describes the span of its central portion. These summaries provide information about the distribution that is different from a mean and standard deviation. Without the actual median change and inter-quartile range, readers cannot assess the central observed change or its spread.
The registry record gives no confidence interval, p-value, or analysis estimate for the primary outcome. A confidence interval, as a general statistical concept, expresses uncertainty around an estimate under the assumptions of the analysis. A p-value is a measure derived from a specified statistical test; it is not a measure of the size or clinical importance of an effect. Neither type of inferential result is available for the primary endpoint in the registry record.
The study is not described as randomized, and allocation is not stated. The record cautions that its groups are not a like-for-like control comparison. This matters because a change observed over time during treatment does not, by itself, separate treatment-associated change from other explanations. A comparison between early and advanced Parkinson disease groups would also not substitute for a randomized control comparison: the groups are defined by disease stage, and the record does not say that they were made comparable for other characteristics.
The safety record lists serious adverse event counts separately for early and advanced Parkinson disease. It records zero serious events in the early group and one in the advanced group. These counts are descriptive registry entries, not a comparative estimate of treatment risk. They do not show whether an event was caused by treatment, and they do not provide a basis for a controlled safety comparison.
Consequently, the posted information supports a description of the study question, endpoint definition, treatment schedule as planned in the summary, and recorded serious-event counts. It does not support a numerical estimate of the primary outcome, a test of the stated symptom questions, or a causal conclusion about treatment. The fact that the study status is completed does not supply the unreported outcome results.
9. Statistical Methods Explained
What does the primary summary measure?
The registry specifies the median change from baseline and the inter-quartile range for the primary endpoint. In general, the median is the middle value after observations are ordered. The inter-quartile range describes the spread of the central half of those observations. These summaries can be useful when the distribution is skewed or contains values far from the centre, because the median is less affected by extreme observations than the mean. That is a general explanation of the statistics; the registry does not report the actual median or inter-quartile range for this endpoint.
The outcome is a change score, with baseline as the reference and visit 3 as the final assessment. The record defines a decrease in UPDRS Part I as the direction interpreted as improvement. A change score is not interchangeable with a final score: it expresses movement relative to baseline. To interpret one, readers would need the observed change and its distribution, neither of which is reported in the registry record.
What can a confidence interval or p-value add?
In general, a confidence interval describes the uncertainty around an estimate under a stated statistical model and procedure. A narrower interval indicates greater precision under those assumptions; a wide interval indicates less precision. It does not remove bias in the design or turn an uncontrolled change into a causal effect. The registry entries do not give a confidence interval for the primary endpoint.
In general, a p-value summarizes how compatible the observed data are with a specified null model, assuming the test's conditions hold. It does not express the probability that a treatment works, and it does not describe the clinical importance of an estimate. The registry record does not report a p-value or a statistical test for the primary outcome. The number of analyses is recorded as zero, which is consistent with the absence of reported analysis results in the registry record, but it does not reveal what analyses may have been planned or conducted outside the registry record.
What do the planning assumptions mean?
The planning assumptions described for sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They frame the effect to detect as a stated fraction of the observed effect. These assumptions describe planning illustrations, not the design of this study: the registry record does not state that the trial used equal allocation, and it does not describe a randomized two-arm comparison. The record also does not report a sample-size justification for the study itself.
As a general concept, a sample-size calculation asks how many observations might be needed under specified assumptions to have a chosen chance of detecting an effect of a particular size using a specified test. Such a calculation depends on the assumed effect, variability, significance level, allocation, and statistical model. A planning result is not an observed study result and is not observed power. The registry entries do not supply the numerical illustration values or establish that the assumptions matched the study's conduct.
The description distinguishes time-to-event illustrations, which give a total number of events using the Schoenfeld method, from other illustrations, which give participants per arm. This is a convention for interpreting planning outputs, not evidence that a time-to-event endpoint was the primary outcome. The primary endpoint recorded is a scale change from baseline. No time-to-event primary outcome is identified in the registry entries.
Why does over-dispersion matter in general?
For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. If ignored, uncertainty estimates can be too small and statistical tests can appear more decisive than warranted. This is a general consideration for count-data methods, not a method reported for this study. The primary outcome is described as a scale score summarized by a median and inter-quartile range, and the registry does not report a model for it.
More generally, the choice of statistical method should match the outcome type, study design, and analysis question. A scale-change analysis, a count-event analysis, and a time-to-event analysis require different assumptions. The registry record does not state the statistical methods used for the primary outcome or the other listed outcomes. It would therefore be inappropriate to infer adjustment methods, covariates, model form, or testing procedures from the endpoint definition alone.
The distinction between estimation and testing is also useful. An estimate describes the observed quantity of interest, while an uncertainty measure indicates how precisely it was estimated under a method. A test addresses a specified hypothesis. Reporting one does not automatically provide the others. Here, the median and inter-quartile range are named as the primary summary approach, but their observed values and any inferential statistics are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and records zero analyses. It does not identify a multiplicity procedure, a hierarchy among outcomes, or a family of hypotheses to be tested. The number of outcome measures alone does not establish how many statistical tests were planned, and the record does not state whether any adjustment for multiple testing was used. The statistical plan is not reported in the registry record.
In general, multiplicity arises when several hypotheses or outcomes are tested. If each is treated as a separate opportunity to find a result, the chance of at least one apparently notable result can increase. Methods for addressing this issue depend on the analysis plan and on which outcomes are considered confirmatory. No such approach can be attributed to this study from the available the registry entries.
The primary analysis population is described as members of the full analysis set who had an UPDRS Part I evaluation at visit 3. The size of that subset is not reported in the registry record. The record does not explain how missing visit-3 measurements were handled, whether any imputation was used, or whether sensitivity analyses were performed. In general, excluding people without the final measurement can affect interpretation if missingness is related to symptoms, treatment, or other factors; the record does not provide information to assess that possibility.
The record also does not report interim analyses, a detailed definition of the full analysis set, or a protocol for handling withdrawals and incomplete assessments. These details should not be inferred from the endpoint description or from the completed status. Without them, readers cannot determine whether the reported analysis population and procedures followed a prespecified statistical plan.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Early PD | 0 | 189 | 0.0% |
| Advanced PD | 1 | 97 | 1.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Early PD | 0 of 189 |
| Advanced PD | 0 of 97 |
Most frequent serious adverse event terms
| Event term | Organ system | Early PD | Advanced PD |
|---|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 0 of 189 | 1 of 97 |
Serious events with the highest arm-level rate: pneumonia (1.0%).
The serious adverse event record lists the early Parkinson disease group with 189 at risk and 0 affected, and the advanced Parkinson disease group with 97 at risk and 1 affected. The top serious term is Pneumonia, reported as 1.0%. These are descriptive entries from the registry record; they are not estimates from a randomized comparison.
In general, an at-risk count identifies the group used for an adverse-event summary, while an affected count records the number meeting that event definition. A small number of recorded events provides limited information about how frequently an event might occur in a broader population. The registry record does not report a comparative safety analysis, uncertainty intervals, or an assessment of whether the recorded event was caused by pramipexole.
The early and advanced disease groups should not be read as treatment and control arms. The record states that allocation is not stated and that the groups are not a like-for-like control comparison. Death counts are not reported in the registry record. These safety figures describe what was entered for the listed categories; they do not, on their own, establish a difference in safety or a causal relationship.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study concerned depressive symptoms during pramipexole treatment in people with early and advanced Parkinson disease. It defines the primary outcome as change in UPDRS Part I from baseline to final visit, visit 3, and states that a decrease is interpreted as improvement. It also describes HADS-D and UPDRS Part III as measures relevant to the study objectives.
However, the record does not report the primary outcome's observed median change or inter-quartile range. It does not report outcome estimates for HADS-D or UPDRS Part III, or inferential results for the primary question. Thus, the registry entries do not show how the scores changed, how precisely any change was estimated, or whether depressive-symptom changes were linked to motor-function changes.
The study record also does not establish a controlled causal effect. It is not described as randomized, allocation is not stated, and the record cautions that the groups are not a like-for-like control comparison. An observed change during a study can be described, but without an appropriate comparison and the relevant results it cannot be attributed to treatment on the basis of these registry entries.
The serious-event entries are likewise descriptive. They record one serious event in the advanced disease group and none in the early group, with Pneumonia as the top serious term. Those entries do not establish that treatment caused an event or that the groups differ in treatment-related risk.
Accordingly, the record is informative about the study's question, planned treatment approach, endpoint definition, and selected safety counts. It is not sufficient to determine the magnitude, precision, or cause of any symptom change. Completion status and enrollment do not replace the missing outcome estimates and analysis details.
13. Why This Trial Matters Statistically
This study illustrates why a clearly defined endpoint and a reported result are both needed for statistical interpretation. The registry describes UPDRS Part I, its score range, the direction treated as improvement, and the assessment times. Those definitions make the intended outcome understandable. But without the observed change and its dispersion, readers cannot tell what the study found on that endpoint.
It also highlights the distinction between a treatment study and a controlled treatment comparison. The record concerns pramipexole treatment but does not describe random allocation, and it explicitly warns that the groups are not a like-for-like control comparison. A before-and-after measurement can describe change over time; by itself, it cannot isolate the contribution of treatment from other influences. Disease-stage categories do not automatically supply a control group.
The record further shows why analysis populations matter. The primary endpoint analysis included only members of the full analysis set with a visit-3 evaluation. Without the size of that subset and information on missing-data handling, readers cannot judge how the analysis population relates to enrollment or how incomplete outcome measurements may affect interpretation.
Finally, planning assumptions should be kept separate from study results. Sample-size illustrations depend on assumed effects and statistical methods, whereas observed outcome estimates describe the data collected. The registry entries identify assumptions used in planning illustrations but do not provide a sample-size justification for this study or numerical primary results. These distinctions help prevent design assumptions, descriptive safety counts, and missing efficacy results from being mistaken for evidence of a treatment effect.
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.
The primary limitation for interpreting the clinical question is that the registry record does not report the primary outcome values. It specifies a median and inter-quartile range for change in UPDRS Part I, but neither is available in the registry record recorded. The record also does not provide outcome values for HADS-D or UPDRS Part III, despite naming them in the study summary.
The design limits causal interpretation. The record does not state allocation and identifies the study as not randomized. It also cautions that the groups are not a like-for-like control comparison. Early and advanced Parkinson disease categories therefore cannot be assumed to provide a controlled estimate of treatment effect.
The primary analysis population is limited to members of the full analysis set with an UPDRS Part I assessment at visit 3. The registry record does not report the size of this analysis population, the number with missing final assessments, or how missing values were handled. It does not describe sensitivity analyses, protocol deviations, treatment adherence, or actual dose exposure.
The record does not report a statistical analysis plan, inferential results, a multiplicity approach, or a sample-size justification. Although planning assumptions are described for sample-size illustrations, those assumptions are not evidence of the study's own design or analysis. Safety information is limited to the listed serious-event counts and term; the record does not provide a controlled safety analysis or establish event causality. These omissions restrict conclusions about effect size, precision, missing-data impact, and treatment-related risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Non-motor Symptoms (Depressive Symptoms) of Parkinson's Disease and Their Course Under Pramipexole Treatment — NCT00651183.
- Registry record last updated 2014-05-20; status last verified 2014-05.
- Results first posted 2010-03-03.
- 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.
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18. Record Summary
The registry identifies a completed study of pramipexole immediate release for depressive symptoms in people with Parkinson disease, including early and advanced disease. The primary completion date is 2008-04, and the recorded enrollment is 286. The brief summary describes a planned investigation of 250 patients by 80 specialists across Austria and an oral dosing schedule with possible titration.
The primary outcome is change from baseline to final visit, visit 3, in UPDRS Part I. The registry describes the median and inter-quartile range as the summary statistics and says a score decrease is interpreted as improvement. The primary analysis population was restricted to members of the full analysis set with a visit-3 evaluation.
Outcome values and statistical analyses are not reported in the registry record. Safety entries list serious adverse events by early and advanced disease group, but the record does not provide a randomized control comparison or establish event causality. Allocation, missing-data procedures, and the statistical analysis plan are not reported.