Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy (NCT00355082), a randomized phase 3 study. The primary outcome is The Percentage of Participants in the 300 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study of conversion to monotherapy for partial epilepsy. The interventions were lamotrigine 300 mg/day and lamotrigine 250 mg/day. The registry records enrollment of 226 participants and a completed study. The study started in 2006-05, with primary completion in 2008-11. These dates describe the registry timeline; they do not provide the duration of follow-up for each participant.

Random allocation is intended to make treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on participant experiences, clinical decisions, and outcome assessment. Those are general design principles, not evidence that all sources of bias were eliminated in this particular study. Details about the randomization procedure, concealment, and who was masked are not reported in the registry record.

The primary endpoint covers a defined part of the treatment phase, from Visit 5 through Visit 9. The registry specifies a 300 mg/day analysis population and describes a control assembled from other similar studies, not from the 250 mg/day arm of this trial. That distinction matters: a randomized two-dose trial design does not, by itself, make every registered endpoint a direct randomized comparison of those doses.

The listed secondary outcomes include discontinuation in the 250 mg/day group, time to discontinuation, meeting escape criteria, changes in seizure frequency, seizure-free participants during a treatment-period window, and seizure-frequency measures during the continuation phase. The registry lists eight outcome measures, but records zero analyses. Numerical outcome estimates, analysis methods, and further details of how the study phases were administered are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The number of participants (par.) starting the Continuation phase (CP) does not equal the number completing the Treatment phase (TP), as 1) the CP was optional, 2) not everyone from the TP was eligible to enter the CP, and 3) par. who failed to qualify for the TP (Baseline Failures) were allowed to enter the CP. All par. start the TP at 300 mg/day.

Double-Blind (DB) Treatment Phase

Reasons for not completing this period:

Continuation Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants in the 300 mg/day dose group who began withdrawal of background antiepileptic drug (AED) (Visit 5) minus any major protocol violators

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 The Percentage of Participants in the 300 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase), measured over From Study Visit 5 through Visit 9 of the Treatment Phase (approximately Week 7 through Week 23).

The primary endpoint is the percentage of participants in the 300 mg/day dose group who prematurely discontinued between Visit 5, approximately Week 7, and Visit 9, the end of the treatment phase, approximately Week 23. The registry defines the calculation as the number who discontinued divided by the number who reached Visit 5, after excluding major protocol violators. The analysis population is described as randomized participants in the 300 mg/day group who began withdrawal of background antiepileptic drug, minus major protocol violators.

Discontinuation is a binary event: each participant either meets the endpoint definition during the specified interval or does not. A percentage can describe how common that event was in the defined population. Such an endpoint can be relevant to study conduct because it captures failure to remain in the treatment phase, but it does not by itself explain the reason for stopping or measure seizure control directly.

The record's description also says its control group used data from other similar studies and was not part of this study. No numerical endpoint result or direct randomized comparison is reported in the registry record. The rationale for selecting this endpoint, and any prespecified threshold for interpreting it, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical concepts below are general explanations. The registry record does not report a complete statistical analysis plan for this trial.

What does a percentage endpoint represent?

For a binary endpoint, each participant is classified according to whether an event occurred under a specified definition and within a specified interval. The event proportion is the number meeting the definition divided by the number included in the relevant analysis population. Expressing that proportion as a percentage makes the frequency easier to describe, but it does not explain the event's cause or establish a treatment effect. In this study, the endpoint is premature discontinuation for a defined 300 mg/day population and interval. The registry gives the calculation rule but does not report its numerical result.

Why does the analysis population matter?

The primary endpoint population is not simply all enrolled participants. It is described as randomized participants in the 300 mg/day group who began withdrawal of background antiepileptic drug at Visit 5, with major protocol violators excluded. Restricting the population in this way affects which participants contribute to the denominator and what question the percentage answers. The record does not report the number in this endpoint population, the number excluded as major protocol violators, or how missing endpoint status was handled. Those details are needed to assess how fully the defined population is represented in an analysis.

What would an uncertainty estimate add?

General statistical interpretation distinguishes an estimate from its precision. A confidence interval communicates uncertainty around an estimate under a particular model and analysis. An interval that is narrow indicates greater precision than a wide interval, while neither width nor location alone resolves questions about bias, clinical relevance, or the appropriateness of the comparison. The registry record does not report a primary endpoint estimate or confidence interval, so precision cannot be evaluated.

Why is the comparator important?

Randomization supports a direct comparison when outcomes are analyzed across the randomized groups in a way that preserves the intended comparison. Here, the primary endpoint description focuses on the 300 mg/day group and says that its control consists of data from other similar studies, not from this study. Such data are not the other randomized arm. General comparisons involving separate studies can be affected by differences in participants, procedures, follow-up, outcome definitions, and other factors. The record does not report the external data, the method for comparing them, or an adjusted estimate. It is therefore not possible to treat this endpoint description as a reported randomized dose contrast.

What can the design information establish?

Randomization, masking, and parallel-group allocation describe features of the study design. In general, randomization can reduce systematic differences between treatment groups at assignment; masking can limit some effects of treatment awareness; and parallel-group designs assign participants to a treatment group for comparison. These design features do not supply missing outcome results. Further operational details, such as the randomization method and masking procedures, are not reported in the registry record.

What does over-dispersion mean in general?

Over-dispersion is a general concern for count outcomes when observed variability exceeds what a simple statistical model assumes. If it is present and not accommodated, standard errors and uncertainty estimates may be unreliable. This trial lists seizure-frequency outcomes, which can involve counts, but the registry record does not identify a count model, report a dispersion assessment, or provide numerical analyses for those outcomes. It would be inappropriate to infer that over-dispersion was present or that a particular correction was used.

What do planning calculations mean?

General sample-size planning asks how many participants per arm would be needed under stated assumptions to detect a specified effect with a chosen significance level and power. The registry record does not report the trial's sample-size justification or design assumptions. The planning illustration described for this analysis uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect defined as a fraction of the observed effect. Such figures are planning illustrations, not observed power and not evidence of an outcome. No numerical primary effect is reported in the registry record from which to interpret such an illustration. The registry record's own sample-size justification is not reported.

More broadly, a statistical method is interpretable only in relation to its estimand, population, outcome definition, and assumptions. The registry describes the primary endpoint and several secondary outcomes, but does not report the analysis methods, effect estimates, uncertainty intervals, or analysis populations for numerical results. Statistical conclusions about comparative efficacy or precision therefore cannot be reconstructed from the registry record.

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("Lamotrigine Extended-release (LTG XR), 300 mg")
n      <- c(93)
events <- c(11)
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  Lamotrigine Extended-release (LTG XR), 300 mg  93  11  11.8  6.1  20.2  6.7  19.9  6.8  20.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary discontinuation endpoint and secondary outcomes concerning discontinuation, escape criteria, seizure frequency, and seizure-free participants. When a study evaluates multiple outcomes, general statistical practice considers multiplicity: the chance of at least one apparently notable finding can increase when many statistical tests are performed. How this issue was handled depends on the prespecified analysis plan, including which outcomes were confirmatory and whether any adjustment or testing hierarchy was planned. Multiplicity methods are not reported in the registry record.

The record lists zero analyses and does not provide numerical results for the primary or secondary outcomes. It therefore does not report which outcomes were analyzed, whether all prespecified analyses were completed, or whether any analyses were exploratory. The protocol's statistical analysis plan and any interim analyses are not reported in the registry record.

The primary endpoint population excludes major protocol violators and is limited to participants who began withdrawal of background antiepileptic drug at Visit 5. The number eligible, the number excluded, and the handling of participants with missing endpoint information are not reported in the registry record. General missing-data methods can produce different estimates depending on assumptions about why information is missing and how missing outcomes relate to observed data. No missing-data method is reported, so the effect of missingness cannot be assessed.

The registry provides no numerical primary effect, confidence interval, or analysis population size for the endpoint. Without these details, the robustness and precision of a comparative result cannot be evaluated. The protocol's intended approach to multiplicity, missing data, and analysis populations is not reported in the registry record.

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: status epilepticus (9.1%), concussion (0.9%), fever (0.9%), generalized seizure (0.9%), liver cancer (0.9%).

The registry reports serious adverse events and other adverse events by group and phase. In the treatment phase, the 300 mg group lists 3 participants with serious events among 112 at risk and 44 with other events among 112 at risk. The 250 mg group lists 5 participants with serious events among 111 at risk and 52 with other events among 111 at risk. These are participant counts, not comparative effect estimates.

For the continuation phase, the 300 mg group lists 3 participants with serious events among 184 at risk and 47 with other events among 184 at risk. The continuation-phase baseline-failures group lists 1 participant with a serious event among 11 at risk and 4 with other events among 11 at risk. Group membership, phase, and the number at risk should be kept in view when interpreting each count. The registry does not report exposure-adjusted event rates or a statistical comparison of these safety counts.

The listed serious-event terms include Status epilepticus at 9.1%, and Concussion, Fever, Generalized seizure, Liver Cancer, and Rash at 0.9% each. The registry information cited does not explain the denominator for these term percentages. Death counts are not reported in the registry record. These listings describe reported safety information; they do not establish that an event was caused by a treatment or allow a comparative safety conclusion on their own.

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

The registry record identifies a randomized, double-blind study of two lamotrigine doses for conversion to monotherapy in partial epilepsy. It defines the primary outcome as premature discontinuation in a specified population and interval and lists additional outcomes concerning discontinuation and seizure frequency. These registry entries describe the research question and the planned outcome scope.

The record does not report numerical primary or secondary outcome analyses. It therefore cannot establish the observed frequency of primary-endpoint discontinuation, the size or precision of a dose contrast, or whether an outcome differed between groups. The primary endpoint's description of a control based on other similar studies also means it should not be mistaken for a direct randomized comparison with the 250 mg/day group.

General interpretation of clinical trial results requires more than an endpoint name or a study purpose. Estimates, uncertainty, analysis populations, and the methods used to address missing data and multiplicity all inform what a result can support. Those numerical analyses and methodological details are not reported in the registry record. The brief summary's stated aim of assessing a lower monotherapy dose is not evidence that the aim was achieved.

The safety entries give counts of participants with serious and other adverse events by listed group and phase, along with several event-term percentages. These are descriptive data. Without an analysis that accounts for comparability, exposure, and uncertainty, they do not establish a treatment-related difference or causation.

Accordingly, the record supports a careful account of the trial design, endpoint definition, and posted safety counts. It does not support a conclusion about whether either dose produced better seizure outcomes, reduced discontinuation, or had a more favorable safety profile.

14. Why This Trial Matters Statistically

This trial is statistically notable for the difference between its randomized design and the way its primary endpoint is framed. The study assigned participants to two lamotrigine doses, but the primary outcome is reported as a percentage within the 300 mg/day group, with a control described as data from other similar studies rather than the randomized 250 mg/day group. Recognizing that distinction is essential when deciding what comparison an endpoint can answer.

The endpoint also has a defined population and time window. It concerns participants who began withdrawal of background antiepileptic drug at Visit 5, excludes major protocol violators, and follows discontinuation through Visit 9. Those boundaries determine which participants and events the statistic would represent. A percentage for that interval would not automatically describe all randomized participants or the entire study duration.

The record illustrates why a trial's stated purpose and outcome list are not substitutes for numerical results. Although the study was intended to assess a lower monotherapy dose, the registry lists zero analyses and does not report a primary estimate, uncertainty interval, or direct dose comparison. Without those elements, readers cannot judge the magnitude or precision of a result.

Finally, the multiple listed outcomes and safety summaries call for careful attention to analysis methods and denominators. The registry record does not report a multiplicity plan, missing-data approach, or statistical comparison of safety counts. This makes the trial useful as an example of how design features, outcome definitions, and reporting completeness jointly govern the conclusions a registry record can support.

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 central limitation for interpretation is that the registry record does not report numerical analyses for the primary endpoint or the listed secondary outcomes. Without outcome estimates and uncertainty measures, the magnitude and precision of any effect cannot be assessed.

The primary endpoint is specific to participants in the 300 mg/day group who began withdrawal of background antiepileptic drug at Visit 5, with major protocol violators excluded. The record does not state the size of this analysis population or how missing endpoint status was handled. Its description also identifies a control based on data from other similar studies and says that control was not part of this study. Details of the external data and any method for comparison are not reported in the registry record.

Although eight outcome measures are listed, the record reports zero analyses. It does not specify which outcomes were analyzed, how multiple outcomes were handled, or whether there were interim analyses. The statistical analysis plan, sample-size justification, and missing-data methods are not reported in the registry record. These gaps prevent assessment of prespecification and analytic robustness.

The adverse-event information is presented as counts by group and phase, with event-term percentages. The record does not report comparative statistical analyses, exposure-adjusted rates, or the denominator for the listed term percentages. Death counts are not reported in the registry record. The safety entries should therefore be read descriptively rather than as evidence of a causal or comparative difference.

These limitations concern what the registry record reports; they do not establish what analyses may have been conducted elsewhere. No conclusion about treatment outcomes can be drawn from the endpoint definitions and safety counts alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy — NCT00355082.
• Registry record last updated 2017-01-02; status last verified 2016-11.
• Results first posted 2009-11-25.
• 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

NCT00355082 is a completed Phase 3 randomized, double-blind, parallel-group study of lamotrigine extended-release 300 mg/day and 250 mg/day for partial epilepsy. The record lists enrollment of 226 participants and describes conversion to monotherapy as the study focus.

The primary endpoint is premature discontinuation in the 300 mg/day group between Visit 5, approximately Week 7, and Visit 9, approximately Week 23, using a defined population that excludes major protocol violators. The endpoint description says its control was assembled from other similar studies and was not part of this trial. The registry lists eight outcome measures and zero analyses; numerical primary and secondary outcome results are not reported in the registry record.

Safety information is listed by group and phase as participant counts with serious or other adverse events. The registry also lists serious-event terms with percentages. These entries are descriptive and are not accompanied by a reported comparative safety analysis.