Special Investigation of Pregabalin for Fibromyalgia (Regulatory Post Marketing Commitment Plan): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Special Investigation of Pregabalin for Fibromyalgia (Regulatory Post Marketing Commitment Plan) (NCT01773993), a registered phase not stated study. The primary outcome is Percentage of Participants With Adverse Drug Reaction.

2. Clinical Question

The registry record also lists outcomes covering serious and unexpected reactions, selected reaction categories, pain and sleep scores, and patient impression at Week 52. These additional measures broaden the description of safety and patient-reported outcomes, but their presence does not establish that every measure has a reported result or analysis. The central question is descriptive: what reactions were recorded among participants treated with pregabalin in this investigation? Without a comparator, the record cannot answer how those observations differ from what would have occurred under another treatment or no treatment.

3. Trial Design

This completed investigation is titled as a regulatory post-marketing commitment plan for pregabalin in fibromyalgia. It lists 534 participants as the enrollment, with a start in 2013-02 and primary completion in 2017-07. The listed intervention is Pregabalin, and the arm description states that subjects were treated with pregabalin.

The record does not list a comparator arm, and allocation is not stated. It explicitly cautions that the investigation is not a randomized comparison and that its arms are not a like-for-like control comparison. Accordingly, its design supports describing observations among treated participants, not estimating a comparative treatment effect from randomized groups.

The primary outcome is the percentage of participants with an adverse drug reaction, assessed from Week 1 to 52 weeks at maximum. An adverse drug reaction was defined as an untoward medical occurrence attributed to LYRICA Capsules in a participant who received them; the physician assessed relatedness. The primary analysis population required meeting the safety analysis criteria and receiving LYRICA Capsules at least once. The adverse-reaction figures list 499 participants at risk.

The record lists 14 outcome measures and no analyses. Secondary outcomes include specified adverse-reaction categories and measures of pain, quality of sleep, and patient impression at Week 52. The registry record does not report the protocol details needed to establish how participants were selected, how follow-up was conducted, or how each outcome was analyzed. These details should not be inferred from the post-marketing purpose or the outcome titles.

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: The analysis population for this outcome measure was the baseline analysis population, which comprised of participants who satisfied the criteria of safety analysis population and had received LYRICA Capsules at least once.

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: Among 534 participants whose survey form was collected, a total of 35 participants were excluded from the baseline analysis population due to no visit after treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Drug Reaction, measured over From Week 1 to 52 weeks at maximum.

The primary endpoint is the percentage of participants with an adverse drug reaction during the period from Week 1 to 52 weeks at maximum. The record defines an adverse drug reaction as an untoward medical occurrence attributed to LYRICA Capsules in a participant who received them. A physician assessed whether an occurrence was related to the capsules. The endpoint therefore concerns both the occurrence of a medical event and the assessment that it was related to the treatment.

In general, a percentage expresses how common a specified outcome was within a defined group. It can make an event count easier to interpret by relating it to the number of participants considered at risk. The posted figures list 152 participants with an adverse drug reaction among 499 at risk. No calculated percentage or inferential analysis is reported in the registry record, so those counts should not be turned into a new percentage when describing the results.

This endpoint is useful for describing the observed safety experience in the treated population. It does not, on its own, establish that treatment caused every event judged related, or determine how the frequency compares with another group. The relatedness assessment is attributed to the physician, and the record does not report further details of that assessment process.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the question a study design can answer. This investigation lists pregabalin as its intervention and does not list a comparator. Its allocation is not stated, and the record warns that it is not a randomized comparison. The available safety results are consequently descriptive observations in treated participants. They cannot be interpreted as a contrast between treatment strategies.

What does a percentage measure?

In general, an event percentage relates the number of participants with a defined event to the number of participants considered at risk for that event. The definition of the event and the population included in the denominator matter: changing either can change the meaning of the percentage. For the primary outcome, an adverse drug reaction was an untoward medical occurrence attributed to LYRICA Capsules, with relatedness assessed by a physician. The posted figures list 152 participants with an adverse drug reaction and 499 at risk. No percentage calculated from these counts is stated in the registry record.

The endpoint’s timeframe is from Week 1 to 52 weeks at maximum. A maximum timeframe does not show that all participants were observed for an equal period. The registry record does not report individual follow-up durations, how incomplete follow-up was handled, or whether the outcome was assessed at consistent visits. Those details would be important for understanding how opportunity to observe reactions varied across participants.

What can counts establish?

In general, a count records how many events or participants met a definition in the data being described. Counts are valuable for transparent reporting, but they do not by themselves indicate the precision of a population estimate or establish a causal effect. A count of participants with an event is also distinct from a count of events: one participant may have more than one occurrence, depending on the outcome definition and reporting method. The record does not provide enough detail to interpret the serious-reaction terms as unique participants or as a complete count of all events.

The listed 4 serious adverse drug reactions among 499 at risk and 0 deaths are safety descriptions. They do not show how those figures compare with a different treatment or with the expected experience in the absence of treatment. Without a comparable group and a stated analysis, the data cannot separate treatment-related risk from other explanations for observed medical events.

What would an interval add?

In general, a confidence interval communicates the uncertainty associated with an estimate under specified assumptions. It complements a point estimate by indicating a range of values consistent with the data and method. An interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the sampling and analysis approach. No interval or inferential analysis is reported for the primary outcome in this registry record. The uncertainty around the descriptive counts therefore is not quantified by a reported interval.

How should planning illustrations be understood?

In general, sample-size planning asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. Such an illustration is not an observed result and does not describe how many participants experienced an outcome. The planning assumptions stated for this record include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. However, this investigation does not list a comparator arm, and no calculated planning counts are reported in the registry record. The stated assumptions should not be mistaken for the design actually used or for evidence of observed power.

In general, over-dispersion refers to variation in data that is greater than a model assumes. It can make standard errors too small if ignored, but the registry record does not identify an over-dispersion model or report analyses that would allow this issue to be assessed. More broadly, the record does not report the statistical model, handling of repeated measurements, covariate adjustment, or sensitivity analyses. No such methods should be assumed from the outcome titles or the study’s post-marketing purpose.

The record’s 14 outcome measures include adverse-event categories and measures of pain, sleep, and patient impression. In general, when many outcomes are examined, the chance of obtaining an apparently notable result by chance can rise if each is tested separately. A multiplicity strategy can address that concern, but none is reported; the record also lists no analyses. Therefore, no claim about statistical significance or multiplicity-adjusted evidence can be made for these outcomes.

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("LYRICA Capsules (Pregabalin)")
n      <- c(499)
events <- c(127)
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  LYRICA Capsules (Pregabalin)  499  127  25.5  21.7  29.5  21.8  29.5  21.8  29.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures and 0 analyses. It identifies the primary adverse drug reaction measure and names secondary outcomes, but does not report analysis results for the listed measures beyond the adverse-reaction figures. No p-values, confidence intervals, or model estimates are reported. Consequently, there is no basis in the record for determining which outcomes, if any, met a statistical decision threshold.

In general, multiplicity arises when several outcomes or hypotheses are examined. If each is evaluated independently, the chance of at least one apparently notable finding can increase. Researchers may prespecify a hierarchy, adjust decision thresholds, or identify outcomes as descriptive. The registry record does not report a multiplicity plan, a hierarchy among secondary outcomes, or whether any adjustment was used. The number of listed outcomes alone does not establish that each was tested.

The record defines the primary analysis population as participants who met the safety analysis criteria and received LYRICA Capsules at least once. It lists 499 participants at risk for the adverse-reaction figures and reports enrollment of 534. The registry record does not explain the difference between those counts, report participant flow, or specify how missing outcome information was handled. It does not report whether participants with incomplete follow-up were excluded, included for the time observed, or addressed by another method.

In general, missing-data methods matter because participants with incomplete outcome information may differ from those with complete information. The appropriate interpretation depends on why information is missing and on the analysis strategy. Neither the reasons for missingness nor a strategy for addressing it is reported in the registry record. The population definition and reported denominator should therefore be kept in view when interpreting the descriptive safety counts.

12. Safety Results

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

Deaths

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: pneumonia bacterial (0.2%), loss of consciousness (0.2%), angina unstable (0.2%), stevens-johnson syndrome (0.2%).

The serious adverse drug reaction figures list 4 among 499 participants at risk, with 0 deaths. These are counts in the pregabalin group, not a comparison with a control group. The listed serious-reaction terms are Pneumonia bacterial, Loss of consciousness, Angina unstable, and Stevens-Johnson syndrome, each reported as 0.2%.

Those term-specific values should not be added together or treated as distinct participants. The registry record does not report the number of participants for each term or explain whether terms could overlap within a participant. It also does not provide a comparator rate or inferential analysis. The figures describe what the record lists; they do not establish how often the same outcomes would occur under another treatment or without pregabalin.

In general, serious-event counts and overall adverse-reaction counts answer different descriptive questions. The primary outcome includes adverse drug reactions attributed by a physician, while the serious-reaction figures concern the serious category. The relatedness assessment and event classification affect what is counted. The registry record does not provide further detail about adjudication or classification procedures, so these figures should be interpreted according to the stated definitions and population.

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

The record documents a completed post-marketing investigation of pregabalin for fibromyalgia and reports adverse-reaction counts among participants treated with LYRICA Capsules. For the primary outcome, it lists 152 participants with an adverse drug reaction among 499 at risk. It also lists 4 serious adverse drug reactions among 499 at risk and 0 deaths. These are descriptive findings for the population and definitions recorded.

They do not establish a comparative treatment effect. No comparator arm is listed, allocation is not stated, and the record cautions that this is not a randomized comparison. Without a like-for-like comparison, observed reaction counts cannot tell whether the frequency differs from that under another treatment or no treatment. Nor do physician assessments of relatedness, as described in the record, prove that treatment caused each event.

The record lists outcomes for selected adverse-reaction categories, pain, sleep, and patient impression, but does not report analyses for them. It lists 14 outcome measures and 0 analyses. The absence of inferential results means there is no reported estimate of statistical uncertainty or test of differences for the primary or secondary outcomes. The available counts should not be extended to unreported results.

In general, a study can be informative for describing events observed in its participants even when it cannot support a causal or comparative conclusion. The value of such a description depends on clear outcome definitions, a well-defined population, and adequate information about follow-up and missing data. The registry record specifies the primary outcome definition and population but does not report several details needed to assess follow-up, missingness, or analytic methods.

Thus, the record supports a limited reading: it reports the stated reaction counts in the listed treated population and names additional outcomes. It does not establish whether pregabalin changes risk relative to a comparator, quantify the precision of the reported counts, or provide results for the other listed measures.

14. Why This Trial Matters Statistically

Post-marketing investigations address the recording of treatment-related information in the context of use after a product has entered practice. This record’s stated purpose was to collect efficacy and safety information about pregabalin in fibromyalgia patients related to appropriate use in daily practice. Its primary measure concerns adverse drug reactions attributed to LYRICA Capsules, with relatedness assessed by a physician.

Statistically, the record illustrates the distinction between describing outcomes and estimating comparative effects. It reports reaction counts among treated participants but does not list a comparator arm or state allocation. The record itself cautions that it is not a randomized comparison. That design context is essential: a safety count can describe what was recorded without showing whether the count is higher or lower than it would be under another condition.

The investigation also makes visible the importance of analysis populations and denominators. Enrollment is listed as 534, while the adverse-reaction figures list 499 at risk. The primary population is defined by safety criteria and receipt of at least one dose. The registry record does not explain the participant flow between these counts, so interpretation should retain the stated denominator rather than assume all enrolled participants contributed to the primary outcome.

Finally, the record lists multiple safety and patient-focused outcomes but reports no analyses. This underscores why outcome registration and outcome results are not interchangeable: a named measure does not itself supply an estimate, uncertainty interval, or statistical conclusion. Clear reporting of results and methods is needed to evaluate both the observed data and their limits.

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 principal limitation for interpretation is the absence of a listed comparator. Allocation is not stated, and the record explicitly says the investigation is not a randomized comparison. The reported safety figures therefore describe participants in the pregabalin group and do not establish a relative risk or treatment contrast.

The registry record reports 534 enrolled participants and 499 at risk in the adverse-reaction figures, but does not explain participant flow or the reason for the difference. The primary population is defined as participants meeting safety analysis criteria who received LYRICA Capsules at least once. The record does not report how incomplete follow-up or missing outcome information was handled.

Although 14 outcome measures are listed, the record reports 0 analyses. It does not report inferential estimates, confidence intervals, p-values, an analysis model, or sensitivity analyses. The record also does not report a strategy for multiplicity, or explain which secondary outcomes have available results. The efficacy-related outcome titles should not be mistaken for findings.

The primary timeframe is from Week 1 to 52 weeks at maximum, but the registry record does not give individual follow-up durations or details of assessment timing. It states that physicians assessed relatedness but does not report further procedures for that assessment. The serious-reaction terms are each listed as 0.2%, without term-specific participant counts or an explanation of overlap.

These reporting gaps limit assessment of precision, completeness, and generalizability. They do not invalidate the counts as recorded, but they constrain conclusions to a description of the listed population and outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Special Investigation of Pregabalin for Fibromyalgia (Regulatory Post Marketing Commitment Plan) — NCT01773993.
• Registry record last updated 2023-10-10; status last verified 2023-09.
• Results first posted 2019-05-03.
• 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.

19. Record Summary

This completed registry record concerns a post-marketing investigation of pregabalin for fibromyalgia. Enrollment is listed as 534; the investigation began in 2013-02 and reached primary completion in 2017-07. Pregabalin is the listed intervention, and no comparator arm is listed.

The primary outcome is the percentage of participants with an adverse drug reaction from Week 1 to 52 weeks at maximum. The posted figures list 152 participants with an adverse drug reaction among 499 at risk, 4 serious adverse drug reactions among 499 at risk, and 0 deaths. Four serious-reaction terms are listed at 0.2% each.

The record lists 14 outcome measures and 0 analyses. It does not report inferential estimates, missing-data methods, or a multiplicity plan. The results should be read as descriptive observations in the treated population, not as a randomized comparison.