Lyrica (Pregabalin) Korean Post Marketing Surveillance Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lyrica (Pregabalin) Korean Post Marketing Surveillance Study (NCT01220180), a registered phase not stated study. The primary outcome is Percentage of Participants Achieving 28 Days Seizure Free Period in Intent-to Treat (ITT) Population.

2. Clinical Question

3. Trial Design

This completed study is a post-marketing surveillance study of pregabalin (Lyrica) in Korea. Its stated purpose was to collect safety and efficacy surveillance data from real-world clinical use for approved indications. The registry lists epilepsy, neuropathic pain, and fibromyalgia among the indications, as well as post-market surveillance. Enrollment is recorded as 4175.

The study began in 2006-07, and primary completion is recorded as 2011-04. The status is COMPLETED. The registry names Pfizer's Upjohn has merged with Mylan to form Viatris Inc. as sponsor. These administrative details identify the record; they do not establish how participants were recruited, followed, or treated.

The record does not describe a randomized comparison: allocation is not stated, and its own note cautions that the arms are not a like-for-like control comparison. The arm descriptions for epilepsy, neuropathic pain, and fibromyalgia are empty. Pregabalin is listed as the drug intervention, but detailed regimens, dose adjustments, and adherence procedures are not reported in the registry record.

The primary outcome is the percentage achieving a 28-day seizure-free period in the epilepsy ITT population, with assessment from baseline through Week 12. Secondary outcomes include changes in sleep interference scores for neuropathic pain and fibromyalgia in ITT and PP populations, and clinician- and patient-rated global impressions of change for neuropathic pain in ITT and PP populations. The registry lists 20 outcome measures and 8 analyses. The protocol, analysis plan, and 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population included participants who received at least 1 dose of the study medication and indication of use was epilepsy.

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 Percentage of Participants Achieving 28 Days Seizure Free Period in Intent-to Treat (ITT) Population, measured over Baseline through Week 12.

The primary endpoint is the percentage of participants in the epilepsy ITT population who achieved a 28-day seizure-free period during the period from baseline through Week 12. The registry defines the ITT population as participants who received at least 1 dose of study medication and whose indication for use was epilepsy. A participant counted as seizure-free if no seizures, partial or other, were reported during a 28-day period.

This endpoint expresses the outcome as a proportion of participants rather than as a change in an average score. In general, a seizure-free proportion is useful for describing how often a specified event-free interval was observed in the defined population. The 28-day interval makes the criterion explicit, while the stated study timeframe identifies when the observation was made. Interpretation depends on the population definition, the completeness of seizure reporting, and how the observation period was handled.

The registry identifies the parameter as NUMBER and the dispersion as a 95% confidence interval, but the primary percentage and confidence interval are not reported in the registry record. Without those estimates, the outcome’s observed frequency and its precision cannot be assessed from the record. The endpoint definition alone is not evidence about the size or direction of an outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event: a participant either met the defined 28-day seizure-free criterion or did not. The endpoint is reported as a percentage, which is a way to express the proportion meeting that criterion in the specified population. This type of outcome differs from a continuous measure, such as a score change, because it classifies each participant according to whether a condition was met.

The population definition is central to interpreting the percentage. The registry defines the primary ITT population as participants who received at least 1 dose and whose indication for use was epilepsy. Thus, the population is not simply everyone enrolled in the overall surveillance study. The number in this epilepsy ITT population is not reported in the registry record, so its denominator cannot be stated from the record. General statistical principle: a percentage is only interpretable alongside its denominator and the rules used to decide which observations contribute to that denominator.

The record identifies a 95% confidence interval as the dispersion measure for the primary endpoint. In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the statistical method. It is not a guarantee that the true value lies within the reported interval, and it does not by itself resolve bias, missing outcomes, or differences in who was observed. Here, the interval itself is not reported in the registry record, so no claim about precision can be made.

What can a confidence interval tell the reader?

For a proportion, a confidence interval provides a range of values compatible with the observed data under a specified method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. These are general interpretations, not findings about this study’s primary estimate: the registry does not report that estimate or its interval. The specific interval method is also not reported in the registry record.

The registry gives a timeframe of baseline through Week 12 and defines seizure freedom by absence of reported seizures during a 28-day period. Those details set the clinical and temporal meaning of the outcome, but they do not disclose how many possible 28-day windows were considered, how overlapping windows were handled, or what rules were used for incomplete observation. These procedures are not reported in the registry record. General statistical principle: endpoint rules for observation windows can affect which participants are classified as having an event or meeting an event-free criterion.

The registry’s parameter label is NUMBER, while the stated unit is percentage of participants. The posted outcome’s numerical value is absent, so the label cannot be used to recover a result. The analysis method used to estimate the percentage or confidence interval is not reported in the registry record. It would be inappropriate to infer a particular test, model, or interval procedure from the endpoint type alone.

How should the nonrandomized design affect interpretation?

The record states that allocation is not stated and that the arms are not a like-for-like control comparison. General statistical principle: random allocation can help balance measured and unmeasured characteristics across comparison groups, whereas observational surveillance does not ensure that balance. Differences in outcomes across groups can reflect who entered each group, the indication for use, or other factors, as well as treatment. The record does not establish a randomized comparison, so a causal treatment effect cannot be inferred from group contrasts.

The enrollment figure of 4175 describes the registered study enrollment, not necessarily the size of the primary analysis population. Those are not interchangeable quantities. The safety results list 4174 at risk in the Pregabalin group, while the primary ITT population has its own definition and its size is not reported. No reconciliation of these population counts is reported in the registry record, and a reason for any difference should not be assumed.

Planning illustrations use assumptions distinct from an observed treatment comparison. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The record notes that these illustrations are planning calculations, not the trial’s own design. For time-to-event calculations, the planning quantity is the total number of events; other planning calculations are expressed as participants per arm. These illustrations are not observed power, and the trial’s own sample-size justification is not reported in the registry record.

In general, over-dispersion matters when variation in the data is greater than a model assumes, potentially making uncertainty estimates too optimistic if it is ignored. That concept does not establish that over-dispersion was present or relevant to this binary endpoint. The model and diagnostic procedures are not reported in the registry record, so no claim can be made about how the analysis handled it.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Pregabalin")
n      <- c(644)
events <- c(427)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Pregabalin  644  427  66.3  62.5  70.0  62.6  69.8  62.6  69.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures and 8 analyses. The outcomes include the primary seizure-free percentage and secondary measures concerning sleep interference and global impressions of change. Examining multiple outcomes creates a general multiplicity concern: when many hypotheses are assessed, the chance of at least one apparently notable result can increase. This is a general statistical issue, not evidence that any particular result in this study is false or that a particular adjustment was required.

A multiplicity plan might specify which endpoint is primary, how secondary outcomes are interpreted, and whether any adjustment is used. The record identifies a primary endpoint but does not report a multiplicity strategy, hierarchy for the secondary outcomes, or adjustment procedure. These details are not reported in the registry record. Without them, the statistical interpretation of multiple analyses cannot be fully assessed. The number of listed outcomes alone does not establish how many tests were performed or how they were related.

The primary analysis population is defined as participants who received at least 1 dose and had epilepsy as the indication. Several secondary outcomes are identified for ITT and PP populations, but the PP population definition is not reported in the registry record. Missing-data rules, imputation procedures, handling of withdrawals, and the amount of missing outcome information are also not reported in the registry record.

Missingness can affect a percentage if participants without an observed outcome are handled differently from participants with observed data. In general, excluding missing outcomes, treating them as failures, or using an imputation method can lead to different estimates, depending on the data and assumptions. No such method should be attributed to this study without registry documentation. The reported endpoint definition and population label do not by themselves disclose the handling of incomplete follow-up.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (0.0%), pneumonia (0.0%), colon cancer (0.0%).

The safety record lists a Pregabalin group with 4174 at risk. It reports 2 participants affected by serious adverse events and 190 affected by other adverse events. These are the registry’s descriptive counts; they do not establish that pregabalin caused the events. The record does not provide a control group suitable for a like-for-like safety comparison.

Deaths are not reported in the registry record. The listed serious-event terms are gastroenteritis, pneumonia, and colon cancer, each displayed with a registry percentage of 0.0%. Those are rounded percentages; the exact event counts for each term are not reported in the registry record. A displayed 0.0% should therefore not be taken as proof that no event occurred or used to reconstruct a count.

In general, adverse-event counts depend on the event definitions, collection period, and rules for deciding whether an event is serious. Those details, including the definitions and attribution procedures used in this study, are not reported in the registry record. The safety figures should be read as recorded surveillance summaries rather than as estimates of comparative risk or evidence of causation.

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

The record establishes what the study set out to observe: safety and efficacy surveillance during real-world clinical use of pregabalin for approved indications in Korea. It defines a primary seizure-free outcome for participants with epilepsy and lists secondary measures related to sleep interference and global impressions of change. It also reports selected adverse-event counts. These details describe the scope of the surveillance record, not the size of a treatment effect.

The primary endpoint result and its 95% confidence interval are not reported in the registry record. Consequently, the posted information does not establish the percentage of the epilepsy ITT population that achieved the specified seizure-free period, nor how precisely that percentage was estimated. The endpoint definition cannot be substituted for the missing outcome estimate.

The design also limits what can be concluded from any apparent group differences. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. General statistical principle: without an appropriate comparison design and sufficient information about group differences, an observed outcome cannot be attributed to treatment alone. This record therefore should not be read as establishing a causal effect.

The adverse-event counts show what was recorded in the Pregabalin group, but they do not by themselves indicate how much risk is attributable to treatment. The absence of reported death data and detailed event definitions further restricts interpretation. The registry record also does not report the missing-data approach, the analysis method, or a multiplicity plan.

In short, the record can inform readers about the study’s surveillance purpose, the planned outcome definitions, and the safety summaries that were posted. It cannot support a conclusion about the primary endpoint’s observed frequency, the precision of that outcome, or a causal treatment comparison from the information reported.

14. Why This Trial Matters Statistically

This study is statistically important as an example of the distinction between a surveillance question and a randomized comparative question. Post-marketing data can describe outcomes and adverse events during real-world clinical use. They may also raise questions for further study. But the registry does not state an allocation method, and it explicitly warns that the arms are not a like-for-like control comparison. Design determines which inferences are justified; the label of an outcome or the size of enrollment cannot replace a suitable comparison.

The primary endpoint is also a useful illustration of why definitions and results must be read separately. The registry gives a specific rule for a 28-day seizure-free period and defines the relevant ITT population. Yet the percentage and confidence interval are not reported in the registry record. A well-described measurement rule makes an outcome interpretable if it is reported, but it does not reveal the observed result when the estimate is absent.

The record includes several kinds of outcomes: a binary seizure-free endpoint, sleep interference score changes, and clinician- or patient-rated global impressions. These measures address different aspects of clinical observation and use different forms of data. Their coexistence makes transparent reporting of population definitions, missing data, analysis methods, and multiplicity especially valuable. The registry lists 20 outcome measures and 8 analyses, while those analytic details are not reported.

Finally, the safety summary illustrates the need to distinguish recorded counts from comparative risk and causality. The posted adverse-event counts are descriptive, and the serious-event terms are shown with rounded percentages. Without full definitions, comparison data, and the primary efficacy estimate, the record offers a limited but instructive view of the statistical questions that post-marketing surveillance can raise.

15. Limitations

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

The most direct limitation is that the primary endpoint’s observed percentage and its 95% confidence interval are not reported in the registry record. Although the endpoint and timeframe are defined, the outcome’s magnitude and precision cannot be evaluated. The size of the primary epilepsy ITT population is also not reported, so the primary denominator is unavailable.

The record does not describe allocation, and it cautions that the arms are not a like-for-like control comparison. Arm descriptions for epilepsy, neuropathic pain, and fibromyalgia are empty. Consequently, the available details do not establish a randomized treatment comparison or support causal interpretation of between-group differences.

Several analysis details are absent. The statistical method for the primary percentage and confidence interval, the definition of the PP population, the handling of missing outcomes, and any multiplicity strategy are not reported in the registry record. The protocol, sample-size justification, interim analyses, and detailed analysis plan are also not reported. These omissions limit assessment of how the stated outcomes were analyzed and how robust any posted results might be.

The safety summary provides aggregate counts, but the registry information does not report detailed adverse-event definitions, attribution procedures, or term-specific counts for the displayed serious-event percentages. Deaths are not reported in the registry record. The listed enrollment and safety population figures describe different registry quantities; the reason they differ is not reported and should not be inferred. These limitations apply to what can be concluded from the registry record, rather than establishing that particular procedures were or were not used in the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lyrica (Pregabalin) Korean Post Marketing Surveillance Study — NCT01220180.
• Registry record last updated 2021-01-25; status last verified 2011-11.
• Results first posted 2011-12-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01220180 is a completed Korean post-marketing surveillance study of pregabalin (Lyrica) for approved indications. The registry records enrollment of 4175, a start date of 2006-07, and primary completion in 2011-04. It lists epilepsy, neuropathic pain, and fibromyalgia as indications.

The primary outcome is the percentage of the epilepsy ITT population achieving a 28-day seizure-free period from baseline through Week 12. The population definition and event criterion are stated, but the endpoint estimate and 95% confidence interval are not reported in the registry record. Safety reporting lists 2 participants affected by serious adverse events and 190 affected by other adverse events in the Pregabalin group, with 4174 at risk. Deaths are not reported in the registry record.

Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. Important analysis details, including missing-data handling and multiplicity procedures, are not reported in the registry record.