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 An Open-Label Long-Term Study Of Pregabalin For The Treatment Of Central Neuropathic Pain (NCT01202227), a non-randomized phase 3 study. The primary outcome is Number of Participants With Peripheral Edema.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01202227 |
| Phase | Phase 3 |
| Condition | Spinal Cord Diseases, Spinal Cord Injuries, Neuralgia |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 104 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer's Upjohn has merged with Mylan to form Viatris Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with central neuropathic pain associated with spinal cord injury, stroke, or multiple sclerosis. The registry describes the safety analysis set as participants who received at least one dose of study medication. The number enrolled was 104; the safety analysis set included 103 participants at risk for the adverse-event summaries. Further eligibility criteria and detailed baseline characteristics are not reported in the registry record.
Intervention
Participants received pregabalin in an open-label, flexible-dose regimen. The study purpose was to assess long-term safety at doses up to 600 mg/day. The regimen description specifies 4 weeks of flexible dosing, followed by 48 weeks of maintenance and a one-week taper. The dose actually taken by each participant, dose changes, and adherence are not reported in the registry record.
Comparator
No separate control group is listed. The study was non-randomized and used a single-group model, so there is no like-for-like comparison with placebo, usual care, or another treatment. The record therefore supports a description of outcomes observed among participants receiving pregabalin, not an estimate of how those outcomes differ from what would have occurred under a comparator.
Primary question
The primary outcome was the number of participants with peripheral edema, assessed at baseline and Weeks 4, 20, 36, 52, and 53. The outcome description specifies edema in the lower extremities and categories of trace, pitting 1 (lower leg), 2 (lower leg to knee), and 3 (above knee and/or presacral edema). The registry record does not report the outcome counts at those time points, so the extent or course of edema cannot be determined from the posted primary-outcome information.
3. Trial Design
This was a completed Phase 3, non-randomized, open-label study with a single treatment group. The registry lists an enrollment of 104 and identifies pregabalin as the intervention. Its stated purpose was to assess the safety of long-term pregabalin use, at doses up to 600 mg/day, among patients with central neuropathic pain related to spinal cord injury, stroke, or multiple sclerosis.
The regimen description gives 4 weeks of flexible dosing, 48 weeks of maintenance, and a one-week taper period. These are features of the stated regimen, not evidence that every participant completed each period or received the same dose. Actual exposure, completion, adherence, and reasons for stopping are not reported in the registry record.
Because the study had no separate comparator and was open-label, participants and study personnel were not masked to treatment assignment. The record does not report random allocation; it explicitly identifies the allocation as non-randomized. Consequently, the design is suited to describing outcomes and adverse events observed during treatment, but it cannot separate treatment-associated changes from changes that might occur over time or for other reasons.
The record gives a start date of 2010-09, a primary completion date of 2012-03, and a status of completed. It lists 16 outcome measures. Detailed eligibility requirements, site information, protocol deviations, and the rationale for the enrollment target 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: Participants who had joined A0081107 study (NCT00407745) were treated with pregabalin or placebo for 16 weeks and underwent tapering phase prior to this study.
Overall Study
| Stage | Pregabalin |
|---|---|
| STARTED | 103 |
| COMPLETED | 84 |
| NOT COMPLETED | 19 |
Reasons for not completing this period:
| Reason | Pregabalin |
|---|---|
| Adverse Event | 16 |
| Withdrawal by Subject | 2 |
| Lack of Efficacy | 1 |
Analysis population for the primary outcome, as defined in the registry: The safety analysis set consists of all participants who received at least one dose of study medication in this long-term study.
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.
| Characteristic | Unit | Pregabalin |
|---|---|---|
| Participants analysed | 103 | |
| Age, Customized: >=18 and <45 years | Participants | 15 |
| Age, Customized: >= 45 and <65 years | Participants | 60 |
| Age, Customized: >=65 years | Participants | 28 |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 81 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Peripheral Edema, measured over Baseline, Weeks 4, 20, 36, 52, and 53.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with peripheral edema at baseline and Weeks 4, 20, 36, 52, and 53. The description concerns edema in the lower extremities and distinguishes trace edema from pitting grades that extend from the lower leg, to the knee, and above the knee and/or presacral area. Thus, the stated endpoint is a count of participants meeting the edema description at each assessment, rather than a continuous measurement of swelling or a severity score averaged across participants.
Counting participants with an event is a binary-outcome approach: each participant is classified according to whether the event was recorded for the assessment. This can make the frequency of a safety finding straightforward to describe. However, the count alone does not convey the duration of edema, its effect on participants, or how severity changed within an individual. The registry record does not report the actual primary-endpoint counts or a statistical comparison across visits. It also does not report the operational rules used to decide how missing assessments or repeated observations were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies peripheral edema as the primary outcome, but it does not report the number of participants with edema at the listed assessment times. Therefore, the primary endpoint cannot be quantified from the record, and no conclusion about its frequency or change over time can be drawn from the posted primary-outcome information. The outcome description does clarify what was intended to be counted and the assessment schedule, but a definition and schedule are not outcome results.
The adverse-event summary reports 19 participants with serious adverse events among 103 at risk and 91 participants with other adverse events among 103 at risk. These are descriptive counts in the pregabalin group. They do not constitute a comparison with a control group, and the record does not provide a causal estimate of the effect of pregabalin on adverse events. The listed serious-event terms include cellulitis and cerebral infarction at 1.9% each, followed by arteriosclerosis coronary artery, anal fistula, colonic polyp, and inguinal hernia at 1.0% each. The registry’s list identifies terms and percentages, but does not provide enough detail to establish severity, duration, relatedness to treatment, or clinical course for each event.
The enrollment of 104 differs from the adverse-event risk count of 103. Those figures refer to distinct record entries: enrollment and the number at risk in the adverse-event summaries. The record describes the safety analysis set as people who received at least one dose. It does not explain the difference between the enrollment and risk counts, so no reason for it should be inferred.
In general, a single-group study can describe events observed during treatment, but it cannot establish what would have happened to the same participants under a different treatment or no treatment. Open-label knowledge of treatment can also affect reporting and assessment, particularly for outcomes involving clinical judgment. These design features matter when interpreting the adverse-event summaries. The record does not report a formal statistical analysis plan, inferential estimates, or uncertainty intervals for the primary endpoint.
Overall, the registry supports a limited descriptive reading of adverse-event counts and a clear account of the planned edema assessments. It does not provide the primary outcome results needed to assess the stated endpoint, and it provides no randomized control comparison. The registry’s completion status indicates that the study is listed as completed; it does not by itself establish that all planned observations were collected or analyzed.
9. Statistical Methods Explained
The methods information in the registry is limited. The study is identified as non-randomized, open-label, and single-group, and the primary outcome is a participant count. A detailed statistical analysis plan, the specific methods used to analyze the primary endpoint, and any inferential results are not reported in the registry record. The explanations below describe general statistical concepts and distinguish them from methods documented for this trial.
What does a participant count represent?
For an outcome recorded as the number of participants with an event, each participant contributes information about whether the event was recorded. The registry’s peripheral-edema endpoint is defined as a count of participants with edema, with severity categories described in the outcome text. The count is intended to describe how many participants met that definition at an assessment. It is not a measure of the average intensity of edema, nor does it show how long the condition lasted.
Repeated assessments can describe whether the number recorded with an event varies over the study schedule. General interpretation requires care: the same participants may contribute observations at multiple assessments, and the observations may be related within a participant. A method that treats repeated observations as independent would not account for that relationship. The registry record does not report whether the analysis accounted for repeated measurements, how it defined the analysis population for each visit, or how missing assessments were handled.
What can a single-group design estimate?
In general, a single-group study estimates or describes outcomes among participants who receive the intervention under the conditions of the study. It does not directly estimate a contrast against a concurrent control group. Without random allocation to a comparator, changes observed over time could reflect treatment, the underlying condition, other care, changes in reporting, or other influences. This is why a before-and-after pattern in a single group cannot, on its own, identify the causal effect of treatment.
Open-label conduct means treatment assignment is known rather than masked. As a general matter, knowledge of treatment can influence participant reporting, clinician assessment, or decisions to record an event. The registry does not report whether the edema assessment was performed by blinded assessors or whether standardized adjudication was used. It also does not report whether investigators assessed the relationship between each adverse event and study medication.
How should adverse-event counts be read?
The record reports 19 participants with serious adverse events among 103 at risk and 91 with other adverse events among 103 at risk. These are counts of participants in the safety summary, not an estimate of risk relative to an untreated or alternative-treatment group. General safety interpretation also distinguishes the number of participants affected from the number of events: one participant can experience more than one event, but the record does not specify the event-level totals or the rules used to summarize repeated events.
The serious-event terms and percentages are descriptive entries. A percentage attached to a term does not, by itself, indicate whether an event was caused by treatment, how long it lasted, or whether it resulted in lasting harm. Such judgments require clinical and event-level information that is not reported in the registry record. The death count is not reported in the registry record.
What does statistical uncertainty add?
In general, a confidence interval describes the range of values compatible with the data under a specified statistical model and repeated-sampling framework. It communicates precision as well as an estimate. A narrow interval indicates greater precision than a wide interval, though neither width nor interval location resolves limitations in study design or measurement. The registry record does not report confidence intervals for the primary outcome or adverse-event summaries.
A significance test, in general, evaluates data against a specified null hypothesis under assumptions about the design and analysis. A p-value is not the probability that a treatment works, and a small p-value would not remove bias from the absence of a control group. No primary-endpoint p-value or inferential analysis is reported in the registry record.
What can planning calculations show?
Sample-size calculations are planning illustrations when they use an observed effect as an assumed target for a hypothetical design. They do not describe the power of the completed study after results are observed. The record does not report the trial’s own sample-size justification or planning assumptions, so a justification for the enrollment target cannot be reconstructed from the registry information. Any planning illustration should be read as conditional on its stated assumptions and not as evidence that the study had a particular probability of detecting an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 16 outcome measures, including several secondary pain measures: total, sensory, and affective scores on the Short-Form McGill Pain Questionnaire at each time point, and the modified Brief Pain Inventory total score at last evaluation. It does not report a statistical analysis plan specifying which outcomes were confirmatory, how outcome families were defined, or whether any adjustment for multiple testing was planned. With multiple outcomes or repeated assessments, the chance of at least one apparently notable result can increase if each is assessed separately. In general, multiplicity procedures address that issue by controlling or otherwise describing the interpretation of multiple tests. No such procedure is reported in the registry record.
The registry lists 0 analyses. This does not establish why no analyses are listed, whether analyses were conducted outside the registry, or whether results were unavailable for other reasons. The registry record does not report the primary endpoint counts, secondary outcome estimates, analysis populations for those outcomes, or missing-data methods.
Missing observations can affect interpretation when participants do not attend every assessment or discontinue treatment. In general, complete-case summaries describe participants with observed data, while other approaches use assumptions about the unobserved outcomes. Different assumptions can lead to different estimates. The record does not say how missing values, withdrawal, death, or incomplete follow-up were handled. The safety analysis set is described as participants who received at least one dose, but the denominator used at every primary-outcome assessment is not reported.
These omissions limit reproducibility and make it difficult to judge whether the posted summaries correspond to prespecified analyses. They also prevent assessment of how missing data and multiple outcomes may affect the interpretation of any apparent pattern.
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 |
|---|---|---|---|
| Pregabalin | 19 | 103 | 18.4% |
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 |
|---|---|
| Pregabalin | 91 of 103 |
Most frequent serious adverse event terms
| Event term | Organ system | Pregabalin |
|---|---|---|
| Cellulitis | Infections and infestations | 2 of 103 |
| Cerebral infarction | Nervous system disorders | 2 of 103 |
| Arteriosclerosis coronary artery | Cardiac disorders | 1 of 103 |
| Anal fistula | Gastrointestinal disorders | 1 of 103 |
| Colonic polyp | Gastrointestinal disorders | 1 of 103 |
| Inguinal hernia | Gastrointestinal disorders | 1 of 103 |
| Melaena | Gastrointestinal disorders | 1 of 103 |
| Tooth development disorder | Gastrointestinal disorders | 1 of 103 |
| Cholangitis acute | Hepatobiliary disorders | 1 of 103 |
| Infected skin ulcer | Infections and infestations | 1 of 103 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pregabalin |
|---|---|---|
| Somnolence | Nervous system disorders | 53 of 103 |
| Weight increased | Investigations | 31 of 103 |
| Nasopharyngitis | Infections and infestations | 26 of 103 |
| Dizziness | Nervous system disorders | 24 of 103 |
| Oedema peripheral | General disorders | 18 of 103 |
| Fall | Injury, poisoning and procedural complications | 13 of 103 |
| Constipation | Gastrointestinal disorders | 8 of 103 |
| Contusion | Injury, poisoning and procedural complications | 8 of 103 |
| Back pain | Musculoskeletal and connective tissue disorders | 8 of 103 |
| Rash | Skin and subcutaneous tissue disorders | 8 of 103 |
Serious events with the highest arm-level rate: cellulitis (1.9%), cerebral infarction (1.9%), arteriosclerosis coronary artery (1.0%), anal fistula (1.0%), colonic polyp (1.0%).
The safety summary gives 19 participants with serious adverse events among 103 at risk and 91 participants with other adverse events among 103 at risk in the pregabalin group. The record also lists serious-event terms and percentages: cellulitis and cerebral infarction at 1.9% each; arteriosclerosis coronary artery, anal fistula, colonic polyp, and inguinal hernia at 1.0% each. These entries describe events reported in the study group. They do not establish that pregabalin caused those events.
Serious adverse events and other adverse events are separate summary categories in the registry. The record does not report the criteria used to classify seriousness, event-level counts, timing, duration, treatment relatedness, or outcomes for individual events. It does not report deaths in the safety summary. Because there is no control group, the counts cannot show whether event frequency was greater or lower than it would have been under another treatment or without study medication. They should be read as descriptive safety information for the participants included in the registry’s risk count, not as a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
The record describes a long-term, open-label study of pregabalin in a single group of patients with central neuropathic pain. Its primary safety outcome was the number of participants with peripheral edema at baseline and specified follow-up visits. The record gives the endpoint definition and the assessment schedule, but it does not report the edema counts. Therefore, it does not provide the primary outcome result needed to describe the observed frequency or pattern of edema.
The adverse-event summaries do provide descriptive counts: 19 participants with serious adverse events and 91 with other adverse events, each among 103 at risk. The serious-event term list adds selected terms and percentages. These data show what the registry records for the treated group, but they cannot indicate how the counts compare with another treatment or with no treatment. The absence of a control group means there is no concurrent counterfactual comparison, and open-label conduct may influence reporting or assessment.
The registry’s description of the regimen and follow-up conveys the intended long-term exposure structure, not proof that each participant completed it. Enrollment was 104, while the adverse-event summaries use 103 at risk; the reason for this difference is not reported. The record also does not provide the primary outcome results, a detailed analysis plan, uncertainty estimates, or missing-data methods.
In general, results from a single-group safety study can contribute descriptive information about events observed during treatment. They cannot, by design alone, establish that an observed event was caused by treatment or that treatment changed its frequency. The registry entry is therefore informative about the study’s stated purpose, design, schedule, and reported adverse-event summaries, while leaving important outcome and analysis details unresolved.
13. Why This Trial Matters Statistically
This study is statistically informative in part because it illustrates the distinction between a study’s objective and the results available in its registry record. The stated purpose was to assess long-term safety, and the primary endpoint was a count of participants with peripheral edema at scheduled assessments. Yet the record does not report the primary endpoint counts. Without those results, the endpoint’s observed frequency and trajectory cannot be evaluated, even though its definition and assessment schedule are described.
The design also matters. A non-randomized, open-label, single-group study can describe what occurred among participants receiving pregabalin, including the adverse-event counts recorded in the registry. It does not create a comparator that would help distinguish treatment-associated effects from the course of the condition, other care, or other influences. That limitation is central to interpreting safety summaries, not a minor technical detail.
The entry also highlights why denominators and analysis populations should be read carefully. The enrollment is 104, while 103 participants are listed at risk in the adverse-event summaries. The safety set is defined as participants who received at least one dose, but the reason for the difference and the denominators at individual edema assessments are not reported. A count is meaningful only with clarity about who was included and how observations were handled.
Finally, the record lists multiple outcomes but does not report the analysis plan, multiplicity procedures, or missing-data methods. These details affect how confidently results can be interpreted and reproduced. The study’s registry information is useful for understanding its structure and reported safety counts, while also showing the limits of drawing statistical conclusions from an incomplete results record.
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 main trial-specific limitation is that the registry record does not report results for the primary peripheral-edema endpoint. The endpoint is described at baseline and Weeks 4, 20, 36, 52, and 53, but no participant counts are given for those assessments. As a result, the primary safety outcome cannot be summarized from the record.
The study had a single treatment group, was non-randomized, and was open-label. There is no like-for-like control comparison, so the adverse-event counts cannot estimate a difference relative to another treatment or no treatment. Open-label assessment may also affect reporting or clinical classification. The record does not report whether outcome assessors were masked, how peripheral edema was assessed in practice, or whether adverse events were judged related to pregabalin.
The enrollment was 104, whereas the adverse-event summaries list 103 at risk. The safety set is described as participants who received at least one dose, but the reason for the denominator difference is not reported. The record also does not provide participant-level exposure, adherence, withdrawals, visit-specific denominators, or reasons for missing assessments.
Further limitations include the absence of a detailed statistical analysis plan, uncertainty intervals, and methods for handling repeated assessments, missing data, and multiple outcomes. Although 16 outcome measures are listed, no analyses are listed in the record. The registry does not explain this. These omissions limit assessment of completeness, precision, and reproducibility, and prevent a fuller statistical interpretation of the study’s stated outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-Label Long-Term Study Of Pregabalin For The Treatment Of Central Neuropathic Pain — NCT01202227.
- Registry record last updated 2021-01-28; status last verified 2013-04.
- Results first posted 2013-05-17.
- 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 describes a completed Phase 3, non-randomized, open-label, single-group study of pregabalin for central neuropathic pain associated with spinal cord injury, stroke, and multiple sclerosis. Enrollment was 104. The regimen description specifies 4 weeks of flexible dosing, 48 weeks of maintenance, and a one-week taper, with doses up to 600 mg/day described in the study purpose.
The primary endpoint was the number of participants with peripheral edema at baseline and Weeks 4, 20, 36, 52, and 53. The outcome counts are not reported in the registry record. The safety summary lists 19 participants with serious adverse events and 91 with other adverse events among 103 at risk. No control group is listed, and detailed analysis, missing-data, and multiplicity methods are not reported.