Study Evaluating Changes in Total Drug Load and Seizure Frequency Using Vimpat® (Lacosamide) in Combination Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Changes in Total Drug Load and Seizure Frequency Using Vimpat® (Lacosamide) in Combination Therapy (NCT01673282), a registered phase not stated study. The primary outcome is The Percent Change in Ratio of Dose and Defined Daily Dose (DDD) for the Drug Load of Concomitant Anti-Epileptic Drugs (AEDs) From Baseline to the End of Observation Period (Day 0 to 6 Months).

2. Clinical Question

The question links two aspects of care: the addition of lacosamide and the amount of other anti-epileptic drug treatment recorded over the observation period. It is a question about change in a defined medication-load measure in clinical practice, not a randomized comparison of lacosamide against another assigned treatment. The group distinction is based on the sodium channel blocking status of baseline drugs. Because the record does not state how treatment-group membership was determined beyond those descriptions, or whether any factors were adjusted for, differences between groups cannot be attributed to the group distinction alone.

The registry gives no numerical mean, standard deviation, confidence interval, or test result for the primary endpoint. Accordingly, the direction, size, and precision of the observed change cannot be assessed from the endpoint information in the registry record. The study's stated aim and endpoint identify the question being asked, but do not establish what the measured change was.

3. Trial Design

This was a non-interventional, observational study of lacosamide used as adjunctive therapy in daily clinical practice. The registry describes two groups according to the baseline anti-epileptic drugs used alongside lacosamide: one group had at least one sodium channel blocking anti-epileptic drug, while the other had none. The record says allocation was not stated. It therefore does not describe a randomized assignment to these groups, and the groups should not be read as equivalent treatment arms in a controlled comparison.

The registry lists an enrollment of 315 and a completed study. It gives the study period as 2012-07 to 2015-07, with primary completion in 2015-07. Enrollment is a study-level figure; the number contributing to the primary endpoint is not reported in the registry record. The Full Analysis Set required at least one dose of lacosamide and at least one valid dose-to-defined-daily-dose ratio at baseline and post-baseline. The record does not give the number meeting those criteria.

The primary endpoint was defined over the interval from baseline (Day 0) to 6 months. It was the percent change in the ratio of dose to defined daily dose for the drug load of concomitant anti-epileptic drugs. The registry describes drug load as the sum, across concomitant anti-epileptic drugs, of each actual dose divided by its defined daily dose. The outcome was specified as a continuous measure summarized by a mean and standard deviation.

The record lists one outcome measure and one analysis. It does not report a detailed statistical analysis plan, the timing or conduct of interim analyses, or a sample-size justification for the study's design. Those details should not be inferred from the listed endpoint or from planning illustrations. As an observational study, the record describes clinical practice rather than a protocol that randomized participants to lacosamide or a control treatment.

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: The Participant Flow consists of subjects in the Safety Set (SS) which received at least 1 dose of VIMPAT. Of the 315 enrolled subjects 311 were included in the SS.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis group for the outcome measure is the Full Analysis Set (FAS). The FAS included all patients who received at least 1 dose of Lacosamide and for whom at least 1 valid ratio of dose and DDD at Baseline and post-Baseline could be calculated.

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: The analysis group for Baseline Characteristics is the Safety Set (SS). The Safety Set consists of all patients who received at least 1 dose of Lacosamide.

6. Primary Endpoint

The registry lists the primary outcome as The Percent Change in Ratio of Dose and Defined Daily Dose (DDD) for the Drug Load of Concomitant Anti-Epileptic Drugs (AEDs) From Baseline to the End of Observation Period (Day 0 to 6 Months), measured over From Baseline (Day 0) to 6 months.

The primary endpoint is the percent change in the ratio of dose to defined daily dose for concomitant anti-epileptic drug load from baseline (Day 0) to 6 months. The registry defines drug load as the sum of the ratios of actual dose to defined daily dose for all concomitant anti-epileptic drugs. The measure therefore represents a combined dose-based summary across the listed drugs, rather than the dose of a single medicine or a seizure-frequency measure.

A defined daily dose is used as a common reference unit for describing drug amounts. In general, expressing actual doses relative to a common reference can help summarize regimens that contain different medicines. Summing those ratios produces a composite measure of the concomitant drug load. A change in that measure describes how the calculated total changed over the stated period; by itself, it does not explain why a change occurred or establish that a particular treatment caused it.

The registry specifies a mean as the summary parameter and a standard deviation as the dispersion measure. In general, the mean describes the average observed change, while the standard deviation describes variability among individual measurements. Neither is a substitute for the endpoint estimate and its uncertainty. The numerical mean and standard deviation are not reported in the registry record, so the actual amount and variability of change cannot be described from the endpoint entry.

The endpoint is relevant to the study's stated interest in medication use after lacosamide was added. It does not, on its own, measure clinical benefit, seizure control, or the appropriateness of any individual regimen. The registry record also lists seizure frequency in the study's broad aim, but the sole listed outcome measure is the drug-load endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summarize?

The outcome is a continuous measure: a numeric value that can take a range of values rather than simply classifying a participant into a category. For each concomitant anti-epileptic drug, the registry defines a ratio using actual dose relative to defined daily dose, then defines drug load as the sum of those ratios. The primary outcome is the percent change in that measure from baseline (Day 0) to 6 months.

In general, a ratio places a dose in relation to a reference amount, while a sum can combine several such ratios into a single regimen-level measure. That summary can be useful when regimens include multiple medicines. It also necessarily compresses information: different combinations of medicines and doses can produce the same overall summary. The drug-load endpoint therefore should be interpreted as the defined composite measure, not as a complete description of every participant's medication regimen.

What do the mean and standard deviation tell a reader?

The registry specifies a mean and standard deviation. In general, the mean is the arithmetic average of the measured values. It gives a central summary but does not show whether the observations cluster closely around that average or vary widely. The standard deviation describes the spread of individual values around the mean; it is not itself an estimate of the mean's precision. A standard deviation can be large even when a mean is estimated precisely in a sufficiently large analysis, or small while uncertainty about the mean remains substantial when few observations contribute.

Neither statistic is reported numerically for the primary endpoint in the registry record. Without the mean, readers cannot describe the observed average change. Without the standard deviation, they cannot describe the reported variability. And without an uncertainty interval or equivalent information, they cannot assess the precision of the mean.

Why distinguish variability from uncertainty?

In general, variability describes differences among participants, whereas uncertainty describes how well the available data estimate a population quantity. A confidence interval is one way to express uncertainty around an estimate. Its interpretation depends on the statistical model and analysis assumptions. It is not a guarantee that the true value lies within a particular interval, and it does not replace consideration of study design or potential bias.

The registry record does not report a confidence interval for the primary result. It also does not give the numerical standard deviation or endpoint sample size. The precision of the outcome estimate cannot therefore be reconstructed from the information recorded. An enrollment count alone is not sufficient to determine precision, because the analysis population may be smaller and the spread of measurements also matters.

What does the observational comparison allow?

The two groups are defined by baseline concomitant anti-epileptic drug use: at least one sodium channel blocking drug in one group and none in the other. The record says allocation was not stated. In general, random allocation helps balance measured and unmeasured characteristics between groups, on average. In a non-randomized comparison, group composition can reflect clinical decisions or participant characteristics. This can complicate interpretation of group differences.

The registry does not report an adjustment strategy or group-specific numerical estimates for the primary endpoint. It is therefore not possible to assess whether any comparison accounted for differences between groups. A descriptive group contrast, even if available, would not automatically be a causal treatment effect. The study's observational character and the missing analysis details should remain part of the interpretation.

How should planning illustrations be read?

In general, sample-size calculations describe how many participants might be needed under stated assumptions to detect an effect of a chosen size with a specified statistical approach. They are planning illustrations, not observed study outcomes and not evidence that a completed study had a particular probability of detecting an effect. The record describes illustrations based on the observed effect, equal allocation between the two groups, a two-sided significance level of 0.05, and a normal approximation. It also describes the target effect as a stated fraction of the observed effect.

The record does not report a sample-size justification for the original study design. The numerical outcome needed to interpret an illustration based on the observed effect is not reported in the registry record. Thus an illustration cannot replace the primary endpoint estimate, and it should not be called observed power. No sample-size figure should be interpreted as the number actually analyzed unless the registry reports that fact.

What can be concluded from the methods record?

The record specifies the endpoint, the summary parameter, the dispersion measure, the observation interval, and the Full Analysis Set criteria. These details help define what an analysis would represent. However, the numerical endpoint findings and several important analysis details are not reported in the registry record. The statistical meaning of an estimate depends not only on the endpoint definition but also on the observed data, the analysis population, and the methods used to handle incomplete observations and potential group differences.

General statistical explanations describe how these methods work; they do not fill in missing study results. Since the numerical estimate and its uncertainty are absent, the registry information supports a description of the intended measurement and its limitations, not a quantitative conclusion about the observed change.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Vimpat + Na Channel Blocking AED", "Vimpat + Non-Na Channel Blocking AED")
n   <- c(149, 153)
m   <- c(-15, -4.4)
sp  <- c(64.8, 31.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Vimpat + Na Channel Blocking AED  149  -15.000  64.800  -25.490  -4.510
CARM  Vimpat + Non-Na Channel Blocking AED  153  -4.400  31.900  -9.495  0.695

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. It does not report a multiplicity plan, such as whether several outcomes or comparisons were tested and how any resulting risk of false-positive findings was handled. The number of listed outcomes alone does not establish the full analysis plan. Details of any additional analyses are not reported in the registry record.

The Full Analysis Set included patients who received at least one dose of lacosamide and for whom at least one valid ratio of dose to defined daily dose could be calculated at baseline and post-baseline. This definition describes who was eligible for the endpoint analysis. The number of participants meeting the definition, the amount and reasons for missing data, and the handling of measurements that could not be calculated are not reported in the registry record.

In general, missing data can affect an estimate when the people or measurements missing from an analysis differ systematically from those observed. Statistical approaches to incomplete data rely on assumptions; different assumptions can lead to different estimates. The registry does not state whether missing values were imputed, whether a complete-case approach was used, or whether sensitivity analyses examined alternative assumptions. Those methods should not be inferred from the Full Analysis Set definition.

The enrollment of 315 is a study-level figure and is not the reported size of the endpoint analysis population. The registry does not provide a participant flow for this outcome or a count of valid baseline and post-baseline measurements. Consequently, the extent to which missing measurements may affect interpretation cannot be assessed from the registry record. The primary endpoint's numerical result is also not reported, preventing assessment of either its magnitude or precision.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: suicidal ideation (0.7%), cardiac arrest (0.6%), palpitations (0.6%), electrocardiogram qt prolonged (0.6%), epilepsy (0.6%).

The registry lists serious adverse event counts separately for the two groups. In the Vimpat + Na Channel Blocking AED group, 153 participants were at risk and 1 was listed as affected by a serious adverse event. In the Vimpat + Non-Na Channel Blocking AED group, 158 were at risk and 6 were listed as affected. These are counts as recorded, not evidence that the group difference was caused by the baseline drug category or by lacosamide. The study was observational, and the record does not describe randomized allocation.

For other adverse events, the record lists 22 affected participants among 153 at risk in the first group and 9 among 158 at risk in the second group. These counts should be kept distinct from the serious adverse event counts. The registry lists serious-event terms including Suicidal ideation (0.7%), Cardiac arrest (0.6%), Palpitations (0.6%), Electrocardiogram QT prolonged (0.6%), Epilepsy (0.6%), and Seizure (0.6%). The record does not provide group attribution for these listed terms.

Deaths are not reported in the registry record; the absence of a reported value should not be read as a reported count of zero. Adverse-event counts do not by themselves establish causation, comparative risk, or the overall safety profile. The registry information does not give further details about event timing, duration, severity beyond the serious classification, or how events were assessed.

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

The study addresses a practical question about the medication load recorded after lacosamide was added to existing anti-epileptic drug therapy. Its endpoint is defined as the percent change in the summed ratio of actual dose to defined daily dose for concomitant anti-epileptic drugs from baseline to 6 months. The Full Analysis Set criteria identify participants who needed valid baseline and post-baseline measurements for that outcome.

What the registry record does not provide is the numerical primary endpoint result. There is no reported mean change, standard deviation, confidence interval, or p-value. Without these, the observed direction, size, variability, and precision of the change cannot be stated. The study's stated purpose and endpoint definition describe what was to be evaluated, not what the estimate showed.

The study also does not establish a randomized comparison between the two baseline drug groups. The groups are defined by sodium channel blocking status of concomitant anti-epileptic drugs, and allocation is not stated. Group differences could reflect factors other than the drug category itself. The registry does not report a statistical adjustment plan that would allow readers to evaluate whether such differences were addressed.

The drug-load measure is not itself a measure of seizure frequency or a direct measure of clinical benefit. The registry's brief summary mentions evaluation of seizure frequency, but the listed primary outcome is drug load, and numerical seizure-frequency findings are not reported in the registry record. Nor can the listed adverse-event counts establish causation or a comparative treatment effect.

In general, a study result is best understood by considering its estimate, uncertainty, analysis population, and design together. Here, the design and endpoint are described, but the numerical result and important analysis details are not reported in the registry record. The appropriate interpretation is therefore limited: the record identifies the measurement and study groups, while leaving the primary observed change and its precision unknown.

14. Why This Trial Matters Statistically

This trial record is statistically useful because it makes an important distinction between a medication's addition in clinical practice and a randomized treatment comparison. The study is explicitly non-interventional and observational. Its two groups are defined by baseline anti-epileptic drug use, and allocation is not stated. That design context is essential when considering what a group comparison could mean: observed differences in an observational setting do not automatically isolate the effect of one treatment feature.

The endpoint also illustrates the strengths and limits of a composite medication measure. Summing actual-dose-to-defined-daily-dose ratios gives a single summary across concomitant anti-epileptic drugs. In general, such a measure can make a multidrug regimen easier to describe with one quantity. At the same time, a single total does not reveal every component of the regimen, and the same total can summarize different combinations of medicines and doses.

The record specifies a Full Analysis Set that requires valid measurements at baseline and after baseline. That makes clear that analysis eligibility depends on observed endpoint data, not solely on study enrollment. Yet the size of this analysis set and the amount of missing data are not reported. This emphasizes why a study-level enrollment figure should not be treated as the denominator for every outcome.

Finally, the record demonstrates the difference between a defined outcome and a reported result. The endpoint and its time frame are described, but the mean, standard deviation, and uncertainty estimate are not reported in the registry record. Statistical interpretation depends on those results as well as design and analysis details. Without them, readers can understand what investigators intended to measure, but cannot assess the observed change or its precision.

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 main limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The endpoint definition is detailed, but no mean percent change, standard deviation, confidence interval, or p-value is listed. It is therefore not possible to describe the observed change or judge its precision from the registry information.

The record gives an enrollment of 315 but does not report the number included in the Full Analysis Set. Because eligibility required valid dose-to-defined-daily-dose ratios at baseline and post-baseline, the analysis may not include every enrolled participant. The number with missing or unusable measurements and the reasons for those data being unavailable are not reported in the registry record.

The observational design limits causal interpretation. The two groups reflect baseline concomitant anti-epileptic drug categories, and allocation is not stated. The record does not describe adjustment for differences between groups, so any group contrast would need cautious interpretation even if numerical estimates were available. It also does not report enough information to evaluate whether participants had comparable baseline characteristics.

The registry lists one outcome measure and one analysis, but does not report a full statistical analysis plan, multiplicity handling, missing-data methods, or interim-analysis details. It does not report a sample-size justification for the original study design. These omissions prevent readers from evaluating several aspects of analysis conduct and prespecification.

The record's brief summary refers to seizure frequency, while the sole listed outcome measure is drug load. Numerical seizure-frequency results are not reported in the registry record. Safety information includes event counts, but deaths are not reported and the listed serious-event terms are not assigned to a treatment group. These limitations constrain conclusions about both efficacy-related outcomes and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Evaluating Changes in Total Drug Load and Seizure Frequency Using Vimpat® (Lacosamide) in Combination Therapy — NCT01673282.
• Registry record last updated 2016-11-15; status last verified 2016-09.
• Results first posted 2016-11-15.
• 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

NCT01673282 is a completed, non-interventional observational study sponsored by UCB Pharma GmbH. It examined adjunctive lacosamide use in daily clinical practice among people with focal epilepsy, with and without secondary generalization. The registry reports enrollment of 315 and distinguishes patients by whether baseline concomitant anti-epileptic drug therapy included at least one sodium channel blocking drug.

The primary outcome was the percent change from baseline (Day 0) to 6 months in the summed ratio of actual dose to defined daily dose for concomitant anti-epileptic drugs. The analysis group was the Full Analysis Set, defined by lacosamide exposure and valid baseline and post-baseline ratios. The endpoint's numerical result, analysis-set size, and uncertainty are not reported in the registry record.

The registry lists serious and other adverse-event counts by group, but does not report deaths or group attribution for the listed serious-event terms. Allocation is not stated, and the record does not describe a randomized comparison.