Effects of Pregabalin on Pain After Total Knee Arthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Pregabalin on Pain After Total Knee Arthroplasty (NCT01333956), a randomized phase 1, phase 2 study. The primary outcome is Postoperative Pain.

2. Clinical Question

The clinical rationale in the registry record is that pain after total knee arthroplasty can be severe, while pain-management side effects may interfere with physical therapy and affect satisfaction. The record also describes uncertainty about dose: lower doses might not provide sufficient pain relief, while higher doses might increase the incidence or severity of side effects. These statements explain the question being studied; they are not findings from the trial.

The randomized comparison was intended to examine several doses rather than only pregabalin against control. That makes the dose-selection question central: the study description asks which regimen is most effective, while the registry record does not provide the outcome estimates needed to compare the regimens. The listed secondary outcomes include opioid-related symptom distress, self-assessed sedation and confusion, Numeric Rating Scale pain, neuropathic pain, opioid usage, and satisfaction. They indicate additional areas the study intended to assess, but their results are not reported in the registry record.

3. Trial Design

The registry describes a randomized, controlled, double-blind trial with quadruple masking and a parallel assignment model. It lists Phase 1 and Phase 2 and an enrollment of 120. The record is marked completed. The listed study period began in 2011-05, with primary completion in 2013-03. These details describe the trial as registered; they do not establish how fully each procedure was carried out.

Four arms are described: control, 50mg, 100mg, and 150mg of pregabalin per dose. The control group is described as receiving 0mg of pregabalin. For each active-dose arm, the record describes two capsules before surgery, one capsule twice a day through the end of postoperative day 14, and one capsule at bedtime on postoperative days 15 and 16. The registry intervention list includes placebo, but it does not give further details about matching capsules or treatment administration.

Random allocation is intended, in general, to make treatment groups comparable with respect to both measured and unmeasured characteristics on average. Masking is intended to limit the influence of treatment knowledge on participants, clinicians, and outcome assessment. The registry uses the term quadruple masking but does not specify which four roles were masked. The word double-blind in the official title and the quadruple-masking entry are both present in the record; a more detailed explanation of masking procedures is not reported in the registry record.

The planned parallel structure means that participants are assigned to one treatment arm rather than crossing between regimens as part of the described design. Although the total enrollment is reported, the registry record does not provide a sample-size justification, recruitment details, allocation concealment procedures, or a detailed protocol for departures from assigned treatment. It also does not report whether the planned arm sizes were achieved for the primary outcome. The adverse-event counts list 30 at risk in each arm, but those safety figures alone do not establish the analysis population for pain outcomes.

The registry lists seven outcome measures and 0 analyses. The outcome listing includes a primary postoperative pain measure and secondary measures. The registry record indicates that the primary outcome has several categories or time points and was not reduced to one comparison in the posted results. Consequently, the design can be described, but the reported record does not support a quantitative estimate of the relative pain outcomes across the four arms.

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:

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 Postoperative Pain, measured over 2 weeks postoperatively.

The primary endpoint is postoperative pain, assessed at 2 weeks postoperatively using a Numeric Rating Scale. The scale is described as ranging from 0=no pain to 10=worst pain imaginable. This endpoint is intended to represent participants’ reported pain at a specified postoperative time, rather than an objective measure of tissue injury or a direct measure of function.

The registry specifies the outcome as a mean, with standard deviation as the measure of dispersion. In general, a mean summarizes the central value of observations, while a standard deviation describes how spread out individual observations are around that mean. Reporting both can help readers understand not only the average pain level but also the variability among participants. Neither measure substitutes for the individual participant responses, and neither alone describes how certain an estimated difference between groups would be.

A Numeric Rating Scale is used in clinical research because it offers a direct, structured way to record a person’s assessment of pain. A defined scale can make responses easier to summarize and compare across groups. General interpretation still depends on the assessment timing, the wording and administration of the scale, and the completeness of responses. The record gives the assessment time and scale anchors but does not describe those additional procedures.

The registry record does not report the arm-specific means or standard deviations, a treatment contrast, a confidence interval, or a significance test for this endpoint. It also does not report a single primary comparison in the posted results. Therefore, the endpoint’s definition is available, but the size and precision of any observed difference in pain are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the trial as randomized, controlled, quadruple-masked, and parallel, and describes Phase 1 and Phase 2. It specifies a continuous primary outcome summarized by a mean and standard deviation. These features indicate the broad design and measurement type, but the record does not report the statistical analysis plan or a primary outcome estimate. The explanations below describe general statistical concepts rather than methods confirmed to have been used in this trial.

What does a mean and standard deviation describe?

For a continuous measure such as a Numeric Rating Scale score, a mean gives a group’s average response. A standard deviation describes the variability of individual observations around that average. If scores vary widely, the mean alone may not represent every participant’s experience well. If scores are tightly clustered, the mean may provide a more representative summary of the group. A standard deviation is not the same as uncertainty in the mean: it describes participant-level spread, while uncertainty in an estimate depends on the data and the analysis.

The record states that the primary outcome is a mean with standard deviation, but does not provide either quantity for any arm. It also does not describe whether the primary analysis would compare group means directly, use an adjusted model, or account for repeated assessments. Those analysis details are not reported in the registry record.

What would a treatment contrast add?

A treatment contrast expresses the estimated difference between groups for a specified outcome and time point. In a four-arm trial, possible contrasts could include comparisons of each dose with control or comparisons among dose groups. General statistical interpretation requires knowing which contrast was prespecified and how it was estimated. The registry record does not report a single primary comparison, and no treatment contrast is reported. It is therefore not possible to identify a preferred dose or quantify a difference from the registered results.

A confidence interval is a general way to show the precision of an estimate. A narrow interval indicates greater precision than a wide interval, given the same method and data context. An interval that includes values representing little or no difference may be compatible with a range of possibilities; that alone does not establish equivalence. Equivalence or noninferiority requires a prespecified margin and a suitable analysis, neither of which is reported in the registry record. No confidence interval for the primary outcome is reported.

A p-value is a general measure of how unusual the observed data would be under a stated null hypothesis and analysis model. It does not measure the size or clinical importance of a difference, and it is not the probability that the null hypothesis is true. A p-value should be read alongside an effect estimate and its uncertainty. The primary p-value and testing procedure are not reported in the registry record.

What is multiplicity, and why can it matter?

Multiplicity arises when researchers make several statistical comparisons or tests. With more tests, the chance of at least one apparently unusual result can increase unless the analysis plan addresses the issue. In this trial, the registry describes four arms and lists seven outcome measures. That does not by itself establish how many tests were planned, which comparisons were primary, or whether any adjustment was intended. The multiplicity strategy is not reported in the registry record.

In general, a prespecified hierarchy, adjusted significance thresholds, or other multiplicity procedures may be used to support interpretation across multiple comparisons. These choices depend on the scientific question and analysis plan. No particular approach should be attributed to this trial based on the registry information. The record’s note that the primary outcome has several categories or time points and was not reduced to one comparison further limits the ability to identify the main inferential result.

What do the planning assumptions mean?

The record describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. These assumptions describe a calculation framework, not evidence that the trial’s actual design used those assumptions. The record does not provide a sample-size justification for the enrollment of 120, nor does it report the effect estimates or planning values needed to interpret the illustrations.

Sample-size calculations are planning tools. They ask how many participants might be required under stated assumptions to target a chosen degree of power for a specified effect. Such calculations are not observed power and cannot establish what the completed study found. A planning illustration based on an observed effect also depends on that effect estimate, which is not reported in the registry record. Any calculated sample sizes should be understood as illustrations under their stated assumptions, not as the trial’s actual enrollment requirement or proof that a result was detectable.

What does the registry say about the analysis?

The registry lists 0 analyses and does not report the primary outcome estimates, a statistical model, the analysis population, missing-data procedures, or a method for accounting for repeated measures. The absence of these details prevents assessment of model assumptions and the robustness of any result. It is not possible to infer an adjusted or unadjusted analysis, an intention-to-treat approach, a per-protocol approach, or any imputation method from the trial design description alone.

In general, analysis choices should match the outcome structure and the design. A continuous score may be analyzed through methods that estimate group means or differences, while repeated observations may require methods that account for within-participant correlation. If variability exceeds what a model assumes, standard errors and tests can be unreliable; general methods that account for over-dispersion or other model departures may then be considered. The record does not indicate that over-dispersion was relevant to this continuous endpoint or that any such method was used. These general considerations cannot substitute for a missing analysis plan or reported result.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures and describes four randomized arms. It names a primary pain outcome and several secondary outcomes, but does not report which comparisons were prespecified for each outcome, how the primary outcome’s several categories or time points were to be handled, or whether any adjustment for multiple testing was planned. The multiplicity strategy is not reported in the registry record. Without that information, a reader cannot determine how the trial intended to control the chance of false-positive findings across outcomes or comparisons.

Missing-data information is also absent. The registry record does not report how many participants contributed pain assessments at 2 weeks postoperatively, whether any observations were missing, why data might have been missing, or how missing responses were handled. In general, missingness can affect interpretation if the participants with observed outcomes differ systematically from those without observed outcomes. The extent and direction of any such effect cannot be assessed without outcome-specific denominators and a stated analysis approach.

The registry record does not identify the analysis population. It does not say whether the primary analysis included all randomized participants, only participants who received assigned treatment, or another defined group. The total enrollment and the safety denominators do not resolve this question: the adverse-event counts are not an analysis-population definition for the pain endpoint.

The record lists 0 analyses. That does not show that no analysis was carried out, but it does mean that no statistical analysis is reported in the registry record. The missing multiplicity, missing-data, and analysis-population details limit reproducibility and prevent a full assessment of how the planned question was translated into a statistical result.

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 0% reporting threshold.

The safety record lists four groups: Control, 50mg Arm, 100mg Arm, and 150mg Arm. Each group has 30 participants at risk for serious adverse events and 0 affected, and 30 at risk for other adverse events and 0 affected. No serious adverse-event terms are listed. These are the posted event counts and denominators for the record.

A count of 0 affected means no events in that category are recorded for the listed group in this record. It should not be read as proof that an event is impossible, nor does it establish that there were no symptoms outside the categories captured or reported. The record does not provide further detail about how adverse events were collected, coded, monitored, or defined, so those procedures are not reported in the registry record.

The death entries are null for all four groups, rather than recorded as zero. A null entry does not provide a numerical death count; the death counts are not reported in the registry record. The listed safety counts also do not establish the number of participants with primary pain measurements or the size of any pain difference. Safety counts and efficacy estimates answer different questions and should be interpreted separately.

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

The registry record describes a trial designed to compare three pregabalin dose regimens with a control group after primary total knee arthroplasty. It specifies a primary pain measure, a Numeric Rating Scale from 0=no pain to 10=worst pain imaginable, assessed at 2 weeks postoperatively. It also records that the study was randomized, quadruple-masked, and parallel, with an enrollment of 120.

Those design details do not reveal the observed pain outcomes. The registry record does not report the group means, standard deviations, treatment differences, confidence intervals, or p-values, and it does not reduce the primary outcome’s several categories or time points to one comparison. As a result, the record cannot establish which dose had the lowest average pain, how large any group difference was, or how precisely an effect was estimated. It also cannot establish that the groups were equivalent or that no effect occurred.

The registry lists secondary outcomes related to opioid-related symptom distress, self-assessed sedation and confusion, Numeric Rating Scale pain, neuropathic pain, opioid usage, and satisfaction. These topics indicate the scope of intended assessment, but their results are not reported in the registry record. Their inclusion does not show that a change occurred in any of these outcomes.

The safety entries record 0 serious and 0 other adverse events among 30 participants at risk in each arm. This is a description of the posted event counts, not a guarantee about the full range of possible harms. The death entries are null, so a death count cannot be inferred from them.

In general, interpreting a randomized trial requires both an estimate of the outcome difference and information about its uncertainty, along with clear definitions of who was analyzed and how missing observations were handled. Those elements are not reported for the primary outcome. The registry record therefore supports a description of the study question, design, endpoint, and posted safety counts, but not a claim that pregabalin did or did not reduce postoperative pain, nor a conclusion about which dose should be preferred.

13. Why This Trial Matters Statistically

This trial is statistically notable for the structure of its question: it compares several dose levels with a control group, rather than testing only one active regimen. A multi-arm design can address dose selection, but interpretation depends on clear, prespecified comparisons and a transparent approach to multiple testing. The registry record does not report that comparison plan or a single analyzed primary contrast.

The primary endpoint is a continuous pain score summarized by a mean and standard deviation. These summaries can describe average response and participant-level variability, but they need an estimated contrast and uncertainty measure to support a comparative interpretation. Neither is reported in the registry record. The endpoint definition is therefore more complete than the posted results.

The registry’s account also highlights the distinction between trial design and analysis reporting. Randomization, masking, and parallel assignment describe how a study is intended to allocate participants and limit certain biases. They do not, by themselves, establish the results or resolve concerns about missing outcome data, analysis populations, or multiple comparisons. Those details are not reported in the registry record.

The record includes a sample-size planning framework using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. This provides assumptions for planning illustrations, but the record does not report the trial’s own sample-size justification or the effect estimate used for planning. Such illustrations cannot substitute for the completed trial’s effect estimate or be interpreted as observed power.

Finally, the posted safety counts illustrate why event data should be presented with denominators and read in context. Zero recorded events in the listed categories is informative about those entries, but does not answer the primary efficacy question or fully characterize safety. The record’s main statistical lesson is that a defined randomized design and endpoint do not by themselves provide a usable estimate of treatment effect; interpretable results also require posted estimates, precision, and analysis details.

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 limitation for interpreting this trial from the registry record is the lack of reported primary outcome results. Although the record defines the scale, assessment time, summary measure, and dispersion measure, it does not provide arm-level pain scores or a treatment contrast. The size and precision of any difference are therefore unknown from the record.

The primary outcome is described as having several categories or time points, and the posted results do not reduce it to one comparison. The registry record does not explain how those categories or time points relate to one another or which comparison was intended as the principal analysis. This prevents a focused interpretation of the study’s central question about dose selection.

Important analysis details are not reported in the registry record, including the statistical model, analysis population, missing-data approach, and multiplicity strategy. The record also does not provide an enrollment justification or describe outcome-specific denominators. Although it lists an enrollment of 120 and 30 participants at risk per group for adverse events, those figures do not establish how many participants contributed to the primary pain analysis.

The masking entry says quadruple, while the official title describes the trial as double-blind. The record does not specify the roles included in masking or explain the relationship between these descriptions. Treatment administration is described by dose and timing, but further implementation details are not reported in the registry record.

The safety information has its own limitations: serious and other adverse-event counts are posted as zero in each group, but collection and coding procedures are not described. Death entries are null rather than numerical counts. These limitations do not show that unreported outcomes or analyses were absent; they mean that the registry record does not report them. Conclusions should remain limited to what the record documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Pregabalin on Pain After Total Knee Arthroplasty — NCT01333956.
• Registry record last updated 2016-05-18; status last verified 2016-04.
• Results first posted 2016-05-18.
• 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 completed randomized, controlled, quadruple-masked, parallel trial of pregabalin after primary total knee arthroplasty. It lists Phase 1 and Phase 2, enrollment of 120, and four arms: control and pregabalin 50mg, 100mg, and 150mg per dose.

The primary outcome is postoperative pain on a Numeric Rating Scale at 2 weeks postoperatively, summarized as a mean with standard deviation. The record lists seven outcome measures and 0 analyses. It indicates that the primary outcome has several categories or time points and is not reduced to one comparison. Primary outcome estimates, uncertainty measures, and analysis details are not reported in the registry record.

For safety, each arm lists 30 participants at risk and 0 affected for serious and other adverse events. Death entries are null. The registry record supports describing the study design, endpoint, and posted safety counts, but does not provide the quantitative primary results needed to judge differences among dose groups.