This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice (NCT00855738), a na phase 4 study. The primary outcome is Percent of Participants Classified as Responders.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00855738 |
| Phase | Phase 4 |
| Condition | Focal Epilepsy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 111 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer's Upjohn has merged with Mylan to form Viatris Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with focal epilepsy receiving first-choice combination therapy in daily clinical practice. The registry reports an enrollment of 111. The primary endpoint population was the Full Analysis Set: participants who took at least one dose of study medication and had post-baseline data for at least one efficacy endpoint. Further eligibility details and baseline characteristics are not reported in the registry record.
Intervention
The study assessed newer antiepileptic drugs used as bitherapy. The registry’s intervention listing names gabapentin, lamotrigine, levetiracetam, pregabalin, oxcarbazepine, tiagabine, topiramate, and zonisamide. The brief summary describes assessment of gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, and topiramate. Drug-specific efficacy results and details of how particular combinations were selected are not reported in the registry record.
Comparator
This was a prospective observational study with a single-group model and no allocation. It therefore did not assign participants to a randomized comparator group. The record does not define a control treatment or a like-for-like comparison between drug groups.
Primary question
The primary question was what percentage of participants were classified as responders at Month 3 and Month 6. A responder had a decrease of at least 50% in seizure number during the last 3 months of treatment before discontinuation, compared with the 3 months before baseline. The registry specifies a 95% confidence interval for this percentage, but numerical primary endpoint results are not reported in the registry record.
3. Trial Design
The Liceo study was a prospective, observational study of newer antiepileptic drugs used as first bitherapy in daily clinical practice for focal epilepsy. It is listed as Phase 4, with a single-group model and allocation recorded as not applicable. Masking was none. Enrollment was 111. The registry lists the study as completed, with a start date of 2007-05 and primary completion date of 2009-06.
Because treatment was observed in clinical practice rather than allocated through a randomized comparison, the study describes outcomes among treated participants; it does not estimate a randomized treatment contrast. The record does not specify a control group, a prespecified comparison between individual drugs, or a method for controlling differences among participants receiving different therapies. The arms are not a like-for-like control comparison.
The registry intervention listing names gabapentin, lamotrigine, levetiracetam, pregabalin, oxcarbazepine, tiagabine, topiramate, and zonisamide. The brief summary lists the assessment of gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, and topiramate. The record does not explain the difference between those listings, give the number of participants receiving each combination, or describe how clinicians selected a treatment.
The primary efficacy outcome was the percentage classified as responders at baseline, Month 3, and Month 6, with the response definition applying to seizure reduction during the last 3 months of treatment. Additional registered outcomes address seizure reduction, seizure freedom, days without crisis, time to first seizure, continuation of study medication, and reasons for discontinuation. Their numerical results are not reported in the registry record. The registry also lists adverse-event counts for all antiepileptic drugs and for pregabalin only.
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: Given the observational nature of the study, the selection of treatment and dose of study medication was independent from participation in the study and was determined by daily clinical practice.
Overall Study
| Stage | All Antiepileptic Drugs |
|---|---|
| STARTED | 111 |
| At Least 1 Dose and 1 Endpoint | 108 |
| COMPLETED | 106 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | All Antiepileptic Drugs |
|---|---|
| Lost to Follow-up | 2 |
| Adverse Event | 1 |
| Subject Defaulted | 1 |
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): intent-to-treat population = those who took at least 1 dose of study medication and had post-baseline data for at least 1 efficacy endpoint. Last Observation Carried Forward (LOCF) captures last 3 months of treatment for subjects who discontinued between Month 3 and Month 6 only. N=number of subjects with evaluable data.
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.
| Characteristic | Unit | All Antiepileptic Drugs |
|---|---|---|
| Participants analysed | 111 | |
| Age, Continuous | years | 45.3 (SD 16.1) |
| Sex: Female, Male: Female | Participants | 52 |
| Sex: Female, Male: Male | Participants | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Percent of Participants Classified as Responders, measured over Baseline, Month 3, Month 6 (last 3 months of treatment).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percent of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants classified as responders. A responder was defined as having a decrease of at least 50% in the number of seizures during the last 3 months of treatment before discontinuation, compared with the number during the 3 months before the baseline visit. The registry gives Month 3 and Month 6 as assessment points and specifies a 95% confidence interval for the percentage.
This endpoint expresses a clinically interpretable change in seizure frequency as the proportion of participants crossing a prespecified response threshold. It can describe how common that threshold response was in the analyzed group. It does not, by itself, quantify the average seizure change for every participant: people with different amounts of improvement can fall into the same responder category, while people just on opposite sides of the threshold are classified differently.
General statistical explanation: a confidence interval conveys uncertainty around an estimated percentage. Its width depends on factors including the amount of information available and the variability of outcomes. It does not guarantee that the true value lies within the interval, and it is not a measure of whether a treatment caused the observed outcomes.
The registry describes the Full Analysis Set as participants who took at least one dose and had post-baseline data for at least one efficacy endpoint. It also states that last observation carried forward was used to capture the last 3 months of treatment for participants who discontinued between Month 3 and Month 6. The numerical responder estimates and confidence limits are not reported in the registry record, so the size and precision of the primary endpoint cannot be assessed from the registered information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a primary endpoint but does not report its numerical estimate. It therefore does not establish what percentage of participants met the responder definition at Month 3 or Month 6, or how wide the corresponding 95% confidence intervals were. Without those values, the magnitude and precision of the primary efficacy finding cannot be described.
The endpoint is a within-group response classification: it compares seizure number during a treatment period with seizure number before baseline. In a prospective observational study, such a change can be described among participants who received the recorded care. It cannot, on its own, separate the effect of medication from other explanations for change, such as differences in participants, changes over time, or other aspects of routine care. The registry record does not report an adjustment strategy that would resolve these concerns.
The design is important to interpretation. Allocation is not applicable, masking is none, and the model is single group. The record does not establish a randomized control comparison. Consequently, results from participants receiving different drugs should not be read as direct evidence that one drug outperforms another. Treatment selection in daily practice can produce groups with different characteristics, and the registry does not report enough information to assess or account for such differences.
Other registered outcomes include percentages with specified seizure reductions, seizure freedom before discontinuation, change in median seizure number, days without crisis, time to first seizure, continuation through Month 6, and time to discontinuation for specified reasons. Although the registry lists these outcomes, it does not report their numerical findings in the information recorded for this analysis. Their definitions and the number of outcome measures alone do not indicate whether outcomes favored any particular drug or what degree of change occurred.
The adverse-event record reports no serious adverse events in the listed groups and reports other adverse events for 7 participants in the all-drug group and 5 in the pregabalin-only group. These counts are descriptive. They do not establish that the listed drugs caused or prevented events, and the record does not provide event terms or comparative analyses. The death fields are not populated, so death counts are not reported in the registry record.
Overall, the registered information supports a description of study design, endpoint definitions, and selected adverse-event counts. It does not support a numerical conclusion about the primary efficacy outcome or a causal comparison among therapies. Any interpretation should preserve that distinction between the study’s stated aims and results actually reported in the registry record.
9. Statistical Methods Explained
The registry identifies the primary outcome as a percentage: the proportion of participants classified as responders. It specifies a 95% confidence interval as the measure of dispersion. A percentage summarizes the frequency of a binary outcome, where each participant is classified as either meeting or not meeting the response definition. The registry record does not report the numerical percentage or its confidence interval.
General statistical explanation: a confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. An interval is not a guarantee about the true value, and its interpretation does not remove design limitations such as the absence of a randomized control group. The method used to calculate the primary endpoint interval is not reported in the registry record.
The responder definition compares seizure counts over two periods: the 3 months before baseline and the last 3 months of treatment before discontinuation. Response requires a decrease of at least 50%. A threshold makes the outcome straightforward to interpret as a proportion, but it compresses information. It does not show the full distribution of seizure changes, and it treats outcomes just on either side of the threshold as different categories even if their actual changes are close. The registry also lists continuous or time-based outcomes, including percent change in median seizure number and time to first seizure, but their analysis methods and results are not reported in the registry record.
The analysis population is described as the Full Analysis Set. It includes participants who took at least one dose and had post-baseline data for at least one efficacy endpoint. This definition indicates that the primary efficacy analysis was not simply defined as every enrolled participant regardless of data availability. The exact number included in each efficacy analysis is not reported in the registry record.
For participants who discontinued between Month 3 and Month 6, the registry states that last observation carried forward captured the last 3 months of treatment. General statistical explanation: last observation carried forward substitutes a participant’s most recent available measurement for a later measurement that is missing. This approach can retain participants in an analysis, but it relies on an assumption that the carried-forward value is a reasonable stand-in for the unobserved outcome. If outcomes change after the last observation, that assumption may not hold. The registry does not report sensitivity analyses comparing this approach with other missing-data methods.
The registry lists 22 outcome measures and 35 analyses. Multiple outcomes and analyses create the possibility of multiplicity: when many statistical questions are examined, the chance of at least one apparently notable result can increase if each is judged separately. General statistical explanation: procedures such as prespecifying a primary outcome or adjusting for multiple testing can address some multiplicity concerns, but the registry record does not report whether any adjustment, hierarchy, or other multiplicity strategy was used. The listed counts alone do not show which outcomes were analyzed together or how results were interpreted.
The study is observational, has a single-group model, and lists allocation as not applicable. General statistical explanation: observational data can show associations and patterns under routine care, but treatment groups may differ for reasons related to treatment choice. Random allocation is one way to balance such differences on average; it is not part of this design. The registry record does not report a causal modeling strategy, covariate adjustment, or a protocol for comparing individual drugs. No comparative treatment effect should therefore be inferred from group membership alone.
Safety counts are also percentages-of-participants outcomes in the general sense that an event is recorded for a participant, but the posted adverse-event information gives counts rather than a full inferential analysis. The registry does not report event-level detail for the listed other adverse events, confidence intervals, or a formal comparison. General statistical explanation: observed event counts describe what was recorded in the stated group; they do not establish causation or quantify the risk of an event outside the study context.
The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect; time-to-event illustrations use total events, while other illustrations use participants per arm. These are planning assumptions, not observed power. The registry does not report the trial’s own sample-size justification or a statistical plan that would clarify whether those illustrations correspond to the original study design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 22 outcome measures and 35 analyses, including the primary responder outcome and secondary measures covering seizure reduction, seizure freedom, time to first seizure, medication continuation, and discontinuation. The record does not report a multiplicity adjustment, a prespecified hierarchy for testing outcomes, or which analyses were considered confirmatory. Without that information, results from multiple outcomes should not be treated as if each were the sole statistical question.
The Full Analysis Set is defined as participants who took at least one dose and had post-baseline data for at least one efficacy endpoint. The registry also specifies last observation carried forward for participants who discontinued between Month 3 and Month 6, to capture the last 3 months of treatment. It does not report the number of participants with missing outcomes, the extent or reasons for missingness, or a sensitivity analysis using other assumptions. Further missing-data handling is not reported in the registry record.
General statistical explanation: missingness matters because outcomes that are unavailable may differ from outcomes that are observed. The implications depend on why data are missing and how the analysis handles them. Carrying a prior observation forward is one assumption, not a direct observation of the later outcome.
The registry does not report the numbers analyzed for each endpoint or whether all participants contributed to every analysis. It also does not report an interim-analysis plan or the statistical plan in enough detail to determine how all analyses were specified. Those omissions limit assessment of the impact of missing data and multiple testing.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Antiepileptic Drugs (Including Pregabalin) | 0 | 111 | 0.0% |
| Pregabalin (Pregabalin Only) | 0 | 40 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Antiepileptic Drugs (Including Pregabalin) | 7 of 111 |
| Pregabalin (Pregabalin Only) | 5 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Antiepileptic Drugs (Including Pregabalin) | Pregabalin (Pregabalin Only) |
|---|---|---|---|
| Somnolence | Nervous system disorders | 4 of 111 | 3 of 40 |
| Weight increased | Investigations | 2 of 111 | 2 of 40 |
| Dizziness | Nervous system disorders | 1 of 111 | 1 of 40 |
| Asthenia | General disorders | 1 of 111 | 0 of 40 |
The registry reports serious adverse-event counts for two groups. For all antiepileptic drugs, including pregabalin, 0 serious adverse events were recorded among 111 participants at risk. For the pregabalin-only group, 0 serious adverse events were recorded among 40 participants at risk. These are descriptive counts in the registry record; they do not establish that serious events could not occur or that the treatments caused no such events.
For other adverse events, the registry reports 7 affected participants among 111 at risk in the all-drug group, and 5 affected participants among 40 at risk in the pregabalin-only group. The registry does not give the event terms or additional details about severity, timing, or attribution for these counts. The listed groups overlap because the pregabalin-only group is included in the all-drug group, so they should not be interpreted as independent comparison groups.
The death fields are not populated. Death counts are therefore not reported in the registry record. No comparative safety analysis or confidence intervals are reported, so these figures should be read as recorded counts rather than as estimates of comparative risk.
12. What the Result Does, and Does Not, Mean
The study addresses how newer antiepileptic drugs were used as first bitherapy for focal epilepsy in daily clinical practice and defines a responder as having at least a 50% decrease in seizure number over the specified treatment period relative to baseline. This provides a clear outcome concept and a practical description of the study’s efficacy question.
However, numerical results for the primary responder endpoint are not reported in the registry record. The stated endpoint and confidence-interval measure do not reveal the observed response percentage, its precision, or whether it changed between Month 3 and Month 6. The secondary outcome definitions likewise do not supply their numerical results. The available information therefore cannot quantify efficacy findings.
The observational, single-group design also shapes what the results could mean. Changes from baseline among treated participants would describe outcomes over time, but without a randomized comparator they would not isolate a treatment effect. The record does not report methods that would support a causal comparison among individual drugs. Nor does the listed enrollment establish that every participant contributed to every efficacy analysis; the Full Analysis Set requires post-baseline efficacy data.
The adverse-event counts provide limited descriptive safety information: the record reports no serious adverse events in the two listed groups and reports other adverse events in each. The event descriptions are not reported, and the groups do not form an independent head-to-head comparison. These counts do not establish causality or support a broad conclusion about comparative safety.
Accordingly, the registry record is informative about the intended clinical question, outcome definitions, study structure, and selected adverse-event counts. It does not show the primary efficacy estimate or support a conclusion that any therapy worked, failed, or was superior. It also does not provide enough statistical detail to judge multiplicity handling, all missing-data decisions, or the robustness of efficacy estimates.
13. Why This Trial Matters Statistically
This study is statistically useful to examine because it asks an effectiveness question in daily clinical practice rather than describing a randomized allocation. The prospective observational design can document how therapies were used and how outcomes were defined over time. It also highlights a central interpretive distinction: observing change in a treated group is not equivalent to estimating what would have happened to the same participants under a different treatment or no treatment.
The responder endpoint turns seizure change into a proportion that is relatively easy to communicate. At the same time, a threshold outcome does not preserve all information about the size and distribution of changes. The registry’s additional listed outcomes—including seizure-free status, changes in median seizure number, and time-to-event measures—reflect different ways of describing clinical course. Their numerical results are not reported in the registry record, so their contribution cannot be evaluated from the registered information.
The record also makes the analysis population and a missing-data approach explicit: it defines the Full Analysis Set and describes last observation carried forward for some discontinuations. These details matter because an efficacy estimate depends on who is analyzed and how unavailable outcomes are treated. The record does not report enough information to assess the sensitivity of findings to those choices.
Finally, the registry lists many outcome measures and analyses but does not report a multiplicity strategy or the numerical primary result. This illustrates why outcome definitions, analysis methods, estimates, and uncertainty all matter together. A protocol-level question and a named endpoint do not substitute for reported results. The study’s design and record can be described, but efficacy and comparative conclusions require information that is not reported in the registry record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting efficacy is that numerical results for the primary responder endpoint are not reported in the registry record. The same applies to the listed secondary outcomes. As a result, response magnitude, precision, and the pattern of outcomes over time cannot be assessed from the registered information.
The observational, single-group design has no randomized control comparison. Treatment selection occurred in daily clinical practice, but the registry does not report how choices were made or whether analyses adjusted for differences among participants or therapies. Direct comparisons between drug groups would therefore be vulnerable to confounding and are not established by the record.
The registry describes a Full Analysis Set based on treatment exposure and post-baseline efficacy data, but it does not give the number analyzed for each outcome or the extent and reasons for missing data. It reports last observation carried forward for participants who discontinued between Month 3 and Month 6, but does not report sensitivity analyses or other missing-data methods. The effect of these decisions cannot be assessed.
The record lists 22 outcome measures and 35 analyses but does not report whether multiplicity was addressed, which analyses were prespecified, or whether interim analyses occurred. A detailed statistical plan is not reported in the registry record. Further characteristics needed to assess applicability, including detailed eligibility criteria and baseline participant information, are also not reported in the registry record.
For safety, the registry gives counts for serious and other adverse events but does not provide event terms for the other-event counts, death counts, or inferential comparisons. These limitations restrict interpretation to the recorded counts and design descriptions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice — NCT00855738.
- Registry record last updated 2021-01-25; status last verified 2010-11.
- Results first posted 2010-07-23.
- 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.
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18. Record Summary
The Liceo study was a completed Phase 4 prospective observational study of newer antiepileptic drugs used as first bitherapy for focal epilepsy. The registry lists a single-group model, no masking, allocation not applicable, enrollment of 111, a start date of 2007-05, and primary completion of 2009-06.
The primary outcome was the percentage classified as responders, defined by a decrease of at least 50% in seizure number during the last 3 months of treatment before discontinuation compared with the 3 months before baseline. The registry specifies assessment at Month 3 and Month 6 and a 95% confidence interval. Numerical primary and secondary efficacy results are not reported in the registry record.
The adverse-event record reports 0 serious adverse events in both listed groups, and other adverse events affecting 7 participants in the all-drug group and 5 in the pregabalin-only group. Event details and death counts are not reported in the registry record. The observational design does not establish randomized treatment comparisons or causal effects.