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 Efficacy and Safety of Eslicarbazepine Acetate as Therapy for Patients With Post-Herpetic Neuralgia (NCT00981227), a randomized phase 2 study. The primary outcome is Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00981227 |
| Phase | Phase 2 |
| Condition | Postherpetic Neuralgia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 567 |
| Arms in the primary outcome | 6 |
| Lead sponsor | Bial - Portela C S.A. |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with post-herpetic neuralgia. The registry record does not report further eligibility details or describe the participants’ baseline characteristics in the posted primary outcome results. It records an enrollment of 567, but the number contributing to the primary outcome differs across the listed treatment arms. The record does not explain those differences.
Intervention
Participants were assigned to one of five eslicarbazepine acetate regimens: 400 mg twice-daily, 600 mg twice daily, 800 mg once-daily, 800 mg twice daily, or 1200 mg once daily. These were separate randomized arms, rather than one pooled eslicarbazepine group in the posted results.
Comparator
The comparator was placebo. The trial is described as randomized, placebo-controlled, parallel-group, double-blind, double-dummy, and multicentre. The registry records quadruple masking. Details about who was masked and how the masking procedures operated are not reported in the registry record.
Primary question
The primary question was whether mean pain changed from baseline to endpoint during treatment, and how that change in each eslicarbazepine arm compared with the change in the placebo arm. Pain was recorded using an 11-point Numeric Rating Pain Scale, from 0 for no pain to 10 for worst possible pain. The endpoint comparison concerns change in the scale score, not a count of pain-free days or a separate responder outcome.
The primary outcome timeframe is baseline and 13 weeks. The registry describes the endpoint as the difference between endpoint mean pain and baseline mean pain. It does not report a separate posted secondary outcome analysis. The central statistical issue is therefore the size and precision of each treatment-arm contrast with placebo, alongside the variation in the pain-change results.
3. Trial Design
The registry classifies this as a phase 2, randomized, parallel-group study with placebo control. Its official title describes a double-blind, double-dummy, randomized, multicentre clinical trial, while the registry’s masking entry is quadruple. Those descriptions establish that masking was part of the design, but the record does not specify the masked roles or provide enough detail to reconcile the terms. The study status is completed.
The registry records enrollment of 567. Five eslicarbazepine acetate dose schedules were compared with placebo: 400 mg twice-daily, 600 mg twice daily, 800 mg once-daily, 800 mg twice daily, and 1200 mg once daily. The posted outcome groups contain 102, 94, 94, 92, and 87 participants in those active-treatment arms, respectively, and 92 in the placebo arm. Safety risk counts are not identical to all of those outcome counts. The registry does not explain the analysis-population definitions or the differences in counts.
The study start is recorded as 2007-11 and primary completion as 2009-01. The primary objective was to assess eslicarbazepine acetate as therapy for patients with post-herpetic neuralgia. The primary outcome uses mean pain change from baseline to endpoint, with the endpoint period described as 13 weeks. The record identifies the outcome as a least-squares mean with standard error, but does not provide the model specification, covariates, handling of missing diary entries, or analysis-population details.
The registry lists placebo and eslicarbazepine acetate as the interventions. Its posted primary results show each dose separately against placebo. The original design assumptions, including any sample-size justification, 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: An up to 2-week baseline was followed by a 1-week titration period, an 8-week maintenance period, and a 2-week safety follow-up period. If subjects had a creatinine clearance between 30 and 60 mL/min, they received half of the assigned dose, and subjects with a creatinine clearance below 30 mL/min were not enrolled in this study.
Overall Study
| Stage | ESL 1200 mg Once Daily | ESL 400 mg Twice-daily | ESL 600 mg Twice Daily | ESL 800 mg Once-daily | ESL 800 mg Twice Daily | Placebo |
|---|---|---|---|---|---|---|
| STARTED | 102 | 94 | 94 | 94 | 90 | 93 |
| Randomized | 102 | 94 | 94 | 94 | 90 | 93 |
| Safety Population | 102 | 94 | 94 | 94 | 90 | 93 |
| Per-Protocol | 69 | 72 | 67 | 68 | 50 | 70 |
| COMPLETED | 80 | 75 | 73 | 73 | 60 | 75 |
| NOT COMPLETED | 22 | 19 | 21 | 21 | 30 | 18 |
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | ESL 1200 mg Once Daily | ESL 400 mg Twice-daily | ESL 600 mg Twice Daily | ESL 800 mg Once-daily | ESL 800 mg Twice Daily | Placebo |
|---|---|---|---|---|---|---|---|
| Participants analysed | 102 | 94 | 94 | 94 | 90 | 93 | |
| Age, Customized: <=18 years | participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: Between 18 and 65 years | participants | 34 | 36 | 35 | 37 | 30 | 38 |
| Age, Customized: >=65 years | participants | 68 | 58 | 59 | 57 | 60 | 55 |
| Sex: Female, Male: Female | Participants | 69 | 55 | 57 | 52 | 64 | 44 |
| Sex: Female, Male: Male | Participants | 33 | 39 | 37 | 42 | 26 | 49 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain, measured over baseline and 13 weeks.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | Points |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures change in mean pain from baseline to the end of the treatment period. Pain was recorded in a patient diary each morning using an 11-point Numeric Rating Pain Scale: 0 means no pain and 10 means worst possible pain. Each entry was intended to represent mean pain over the previous 24 hours.
For baseline, the registry defines mean pain as the mean of the last four available daily ratings in the seven days before randomization. For endpoint, it defines mean pain as the mean of the last four available daily ratings in the last seven days of treatment. The recorded change is endpoint mean pain minus baseline mean pain. A negative change therefore represents a lower mean pain score at endpoint than at baseline; that description concerns the direction of the scale change and is not, by itself, a conclusion about treatment benefit.
A continuous score retains more information about the amount of change than a simple classification such as improved or not improved. Comparing the mean changes between randomized arms can estimate how the average change differs between each regimen and placebo. The mean is useful for summarizing a group, but it does not show how individual participants’ experiences were distributed. The registry reports least-squares means and their standard errors for the arms. The statistical model behind those least-squares means is not reported in the registry record.
7. Results Posted in the Registry
- ESL 1200 mg Once Daily: mean -1.94 versus -1.54 on control; difference -0.40 (95% CI -0.99 to 0.19), standardized effect d = -0.19; z-test p = 0.186.
- ESL 400 mg Twice-daily: mean -1.98 versus -1.54 on control; difference -0.43 (95% CI -1.04 to 0.17), standardized effect d = -0.21; z-test p = 0.160.
- ESL 600 mg Twice Daily: mean -1.68 versus -1.54 on control; difference -0.14 (95% CI -0.74 to 0.47), standardized effect d = -0.06; z-test p = 0.661.
- ESL 800 mg Once-daily: mean -1.66 versus -1.54 on control; difference -0.12 (95% CI -0.73 to 0.49), standardized effect d = -0.06; z-test p = 0.703.
Mean difference: ESL 1200 mg Once Daily
95% CI: -0.99 to 0.19
Recalculated from the posted summary statistics
8. Statistical Interpretation
Mean pain decreased from baseline in every posted arm, including placebo. The least-squares mean changes were -1.945 for 1200 mg once daily, -1.979 for 400 mg twice-daily, -1.68 for 600 mg twice daily, -1.663 for 800 mg once-daily, and -2.083 for 800 mg twice daily. The placebo mean change was -1.544. These are within-arm changes; by themselves, they do not estimate the difference attributable to treatment compared with placebo.
The recalculated comparisons are unadjusted contrasts of each active arm with placebo based on the posted summary statistics. Each estimated contrast is negative, corresponding to a larger mean reduction in the active arm than in placebo. The reported unadjusted p-values are 0.186 for 1200 mg once daily, 0.16 for 400 mg twice-daily, 0.661 for 600 mg twice daily, 0.703 for 800 mg once-daily, and 0.089 for 800 mg twice daily. Each confidence interval includes zero. Thus, the posted summary data do not give a precise separation from no mean difference for any of these recalculated comparisons.
The size of the estimated contrasts varies across regimens. The 800 mg twice-daily contrast has the largest magnitude among the posted contrasts, while the 600 mg twice-daily and 800 mg once-daily contrasts are comparatively close to zero. This variation should not be read as proof that one regimen differs from another: the reported comparisons are each against placebo, and no direct active-dose comparisons are posted. The registry record also does not report a multiplicity adjustment. Considering several unadjusted comparisons makes the p-values less suitable as stand-alone evidence for selecting a regimen.
The endpoint arm counts range from 87 to 102, and the arm estimates have standard errors. Those standard errors indicate uncertainty in the estimated arm means, not the spread of individual pain scores. The recalculated comparisons use an approximate pooled standard deviation derived from the posted standard errors, so they are simple summary-statistic calculations rather than a substitute for the trial’s full analysis. The sponsor’s analysis is not displaced by these recalculations; the registry record does not post analysis records for the primary outcome from which a sponsor-model result could be described.
Overall, the posted results show reductions in mean pain scores in all arms and estimated active-versus-placebo contrasts favoring larger reductions in the active arms. The uncertainty intervals also remain compatible with no mean difference. The registry record does not report the original statistical analysis plan, missing-data methods, or an adjusted primary analysis, so conclusions should remain limited to these posted summaries and recalculations.
9. Statistical Methods Explained
The primary outcome is continuous: it is a mean change in pain-scale points. A continuous outcome can be summarized by an average for each arm, while the standard error describes the uncertainty around the estimated average. The standard error is not the same as the standard deviation. A standard deviation describes variation among observations; a standard error describes how precisely an average has been estimated. The registry reports least-squares means and standard errors, but does not report the model details that produced the least-squares means.
What does a change score represent?
The registered change is endpoint mean pain minus baseline mean pain. Since lower pain scores are toward the lower end of the scale, a negative change indicates that the endpoint average is lower than the baseline average. The arm mean is a within-arm summary. A change within the placebo arm can occur during a trial as well, so the randomized comparison is more informative for assessing the difference between treatment assignments than looking at change in one arm alone.
The posted recalculated contrasts compare each eslicarbazepine arm with placebo. They are described as mean differences and are based on the arm summary statistics, without adjustment. A negative contrast means the estimated mean change in that active arm is more negative than the placebo mean change. It does not establish that the true group difference is nonzero. The confidence interval and p-value quantify uncertainty under the assumptions of the calculation.
How should the confidence interval be read?
A confidence interval gives a range of values compatible with the estimate under the statistical procedure and its assumptions. It is useful to consider both the direction and width of the interval. An interval that includes zero means the data remain compatible with no difference in mean change, as well as with differences in either direction represented within the interval. It does not mean the groups are known to be identical. Nor does an interval alone tell whether a difference would matter to patients; the registry record does not report a threshold for a clinically important difference.
The reported unadjusted p-values test a null hypothesis of no mean difference for each recalculated comparison, under the calculation’s assumptions. A p-value is not the probability that the null hypothesis is true, nor a measure of the size or importance of the difference. The five comparisons are individually unadjusted. The registry record does not report whether the trial’s original analysis used a multiplicity procedure or what decision rule it used.
Why is the pooled variability approximate?
For the recalculated contrasts, the pooled standard deviation is marked approximate and is derived from the posted standard errors and arm sizes. The resulting contrasts and intervals are unadjusted summary-statistic recalculations, not a reproduction of a full participant-level model. These calculations do not incorporate unreported covariates, repeated-measure structure, or any other model features. The record does not report whether the primary analysis included such features.
In general, pooling variability assumes that the compared groups can be summarized with a common underlying spread for the purpose of the contrast. If spreads differ substantially, a pooled estimate can misrepresent uncertainty. The summary data do not provide enough detail to assess that issue fully. More generally, departures from model assumptions, influential observations, or diary measurement patterns can affect a continuous-outcome analysis. The registry record does not report diagnostic checks.
What can the randomized design contribute?
Random assignment is intended to make groups comparable on average at the time of assignment, supporting a causal comparison when the trial is conducted and analyzed appropriately. Masking can reduce some sources of behavior or assessment bias, but the registry’s masking entry does not give operational details. The registry identifies a parallel-group design, meaning participants were assigned to a group and outcomes were compared across groups. The record does not describe adherence, treatment discontinuation, or how participants with incomplete diary data were handled.
These methodological considerations explain why the posted arm means are informative but incomplete. The observed summaries describe the analyzed data. The uncertainty estimates depend on statistical assumptions, and the record does not contain enough detail to verify the original analysis or its missing-data strategy. The recalculated results should consequently be distinguished from a fully documented trial analysis.
10. Confidence Intervals and Precision
The mean-change estimates have standard errors, and the recalculated treatment-versus-placebo contrasts have confidence intervals. Those intervals include zero for all five comparisons. This means that the unadjusted summary-data calculations do not exclude a zero mean difference at the interval’s stated confidence level. It does not establish that the treatments and placebo have identical effects, and it does not show that every value in an interval is equally plausible.
The intervals vary in width across comparisons. Their width reflects both the estimated variability and the amount of information in the compared arms. Wider intervals represent less precision: they allow a broader range of possible mean differences. The confidence intervals are consistent with the p-values being above 0.05 in all recalculated comparisons. The registry record does not specify a multiplicity-adjusted confidence procedure, so these should be read as unadjusted intervals for individual comparisons.
Precision is not the same as clinical importance. A narrow interval can still include effects that matter, depending on the context, and a statistically distinguishable estimate need not be important to patients. No threshold for an important change in mean pain is reported in the registry record. The record also does not provide participant-level outcome distributions, so the intervals cannot describe the range of individual responses.
These intervals come from approximate, unadjusted recalculations using posted summary statistics, rather than a reported model-based analysis. The original analysis method, missing-data handling, and any adjustment for multiple comparisons are not reported in the registry record. The intervals therefore characterize the recalculation, not a verification of every feature of the trial’s intended analysis.
11. Planning a Similar Trial: Sample Size
This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 435 | 582 |
| 75% of the observed effect | 773 | 1,035 |
| 50% of the observed effect | 1,739 | 2,328 |
The sample-size illustrations translate an observed contrast into hypothetical future-study planning numbers; they are not counts from this trial. For these continuous outcomes, the figures are participants per arm, not total events. The planning calculations assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each row plans for a stated fraction of the observed effect. The registry record’s own original design assumptions and sample-size justification are not reported.
The 80% power column gives the estimated participants per arm for a hypothetical study designed to have an 80% chance of detecting the effect used in that row, if the assumptions hold and that effect is the true one. The 90% power column gives the corresponding participants per arm for a higher chance of detecting that same assumed effect. These are planning illustrations, not observed power.
Rows planning for 75% or 50% of the observed effect assume smaller effects than the row using 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants per arm under the same assumptions. The figures can become especially large when the observed contrast is small. This does not mean that a future study must use those exact sample sizes: its target effect, outcome variability, design, analysis, allocation, and other planning choices may differ.
The illustrations are based on the recalculated observed comparisons and therefore inherit their limitations, including approximate variability and the uncertainty of the observed effect. An observed effect can be a poor estimate of the effect a future study should target. These values should be used to understand how assumptions affect planning, not as evidence that the completed trial had a particular probability of success.
12. How the Sample Size Is Derived
Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z1−α/2 = 1.960) and the desired power (z1−β = 0.842 for 80% and 1.282 for 90%).
Formula
n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.
Worked calculation for this trial
- Observed difference Δ = -0.401; pooled standard deviation σ = 2.108.
- n = 2 × (1.96 + 0.842)2 × 2.1082 / -0.4012 = 434.7, rounded up to 435 participants per arm for 80% power.
The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).
R code
alpha <- 0.05
z_a <- qnorm(1 - alpha / 2) # two-sided
delta <- -0.4006 # observed difference in means
sigma <- 2.10807138898133 # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))
# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")
# Simulation: exact two-sample t-test using simulated means and variances
set.seed(981227)
n <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n)) # difference in sample means
s2 <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1)) # pooled sample variance
tstat <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))
Output from running the code
100% of observed effect: n per arm = 435 (80% power), 582 (90% power)
75% of observed effect: n per arm = 773 (80% power), 1,035 (90% power)
50% of observed effect: n per arm = 1,739 (80% power), 2,328 (90% power)
power.t.test: 435.7
Simulated power at n = 435 per arm: 0.800 (20000 replicates)The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.
13. Multiplicity, Missing Data and Analysis Populations
The registry reports five active-treatment comparisons with placebo. The recalculated p-values are unadjusted, and the confidence intervals are individual unadjusted intervals. When several hypotheses are tested, the chance of at least one false-positive finding can increase if each is judged separately at the same threshold. Statistical methods can address that issue, for example by adjusting the testing procedure or identifying a primary comparison in advance. Which approach was used in the trial’s original analysis is not reported in the registry record.
The primary endpoint is described, but the record does not provide a full statistical analysis plan, a hierarchy for testing the five regimens, or a stated multiplicity strategy. It also does not report interim analyses or stopping rules. The record lists zero secondary outcomes posted and zero analysis records, although it does post primary outcome arm summaries and the summary-statistic recalculations described in the results. No secondary outcome findings can be assessed from this record.
Missing data matter because the endpoint depends on diary ratings near baseline and near the end of treatment. The definition uses the last four available ratings in each specified seven-day period, but that definition does not explain what happened when fewer ratings were available or how missing endpoint data were handled. The registry record does not report imputation, a missing-data model, sensitivity analyses, or the assumptions used about missingness.
The record also does not identify the primary analysis population or state whether results were analyzed by assigned treatment, treatment received, or another population definition. Outcome group counts differ across arms, and safety risk counts differ from some outcome counts, but the record does not explain why. These omissions limit assessment of the analysis populations and the robustness of the posted estimates. They do not establish that the trial analysis was inappropriate; they mean that key details cannot be evaluated from the registry record.
14. 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 |
|---|---|---|---|
| ESL 1200 mg Once Daily | 1 | 102 | 1.0% |
| ESL 400 mg Twice-daily | 4 | 94 | 4.3% |
| ESL 600 mg Twice Daily | 4 | 94 | 4.3% |
| ESL 800 mg Once-daily | 2 | 94 | 2.1% |
| ESL 800 mg Twice Daily | 1 | 90 | 1.1% |
| Placebo | 0 | 93 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ESL 1200 mg Once Daily | 48 of 102 |
| ESL 400 mg Twice-daily | 41 of 94 |
| ESL 600 mg Twice Daily | 42 of 94 |
| ESL 800 mg Once-daily | 46 of 94 |
| ESL 800 mg Twice Daily | 49 of 90 |
| Placebo | 29 of 93 |
Most frequent serious adverse event terms
| Event term | Organ system | ESL 1200 mg Once Daily | ESL 400 mg Twice-daily | ESL 600 mg Twice Daily | ESL 800 mg Once-daily | ESL 800 mg Twice Daily | Placebo |
|---|---|---|---|---|---|---|---|
| Arthritis reactive | Musculoskeletal and connective tissue disorders | 0 of 102 | 0 of 94 | 1 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 102 | 1 of 94 | 0 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Biliary tract infection | Infections and infestations | 1 of 102 | 0 of 94 | 0 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Dizziness | Nervous system disorders | 0 of 102 | 1 of 94 | 0 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 102 | 0 of 94 | 0 of 94 | 1 of 94 | 0 of 90 | 0 of 93 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 0 of 102 | 0 of 94 | 1 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Herpes zoster | Infections and infestations | 0 of 102 | 1 of 94 | 0 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Hyponatraemia | Metabolism and nutrition disorders | 0 of 102 | 0 of 94 | 0 of 94 | 0 of 94 | 1 of 90 | 0 of 93 |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 102 | 1 of 94 | 0 of 94 | 0 of 94 | 0 of 90 | 0 of 93 |
| Myocardial infarction | Cardiac disorders | 0 of 102 | 0 of 94 | 0 of 94 | 1 of 94 | 0 of 90 | 0 of 93 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ESL 1200 mg Once Daily | ESL 400 mg Twice-daily | ESL 600 mg Twice Daily | ESL 800 mg Once-daily | ESL 800 mg Twice Daily | Placebo |
|---|---|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | 9 of 102 | 4 of 94 | 8 of 94 | 5 of 94 | 11 of 90 | 2 of 93 |
| Nausea | Gastrointestinal disorders | 11 of 102 | 3 of 94 | 6 of 94 | 3 of 94 | 8 of 90 | 1 of 93 |
| Vomiting | Gastrointestinal disorders | 7 of 102 | 4 of 94 | 7 of 94 | 4 of 94 | 6 of 90 | 2 of 93 |
| Headache | Nervous system disorders | 5 of 102 | 3 of 94 | 5 of 94 | 3 of 94 | 8 of 90 | 4 of 93 |
| Somnolence | Nervous system disorders | 6 of 102 | 3 of 94 | 2 of 94 | 1 of 94 | 10 of 90 | 2 of 93 |
| Vertigo | Ear and labyrinth disorders | 5 of 102 | 3 of 94 | 4 of 94 | 3 of 94 | 3 of 90 | 4 of 93 |
| Fatigue | General disorders | 4 of 102 | 6 of 94 | 4 of 94 | 4 of 94 | 3 of 90 | 1 of 93 |
| Diarrhoea | Gastrointestinal disorders | 2 of 102 | 2 of 94 | 5 of 94 | 1 of 94 | 2 of 90 | 4 of 93 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 102 | 2 of 94 | 4 of 94 | 1 of 94 | 4 of 90 | 1 of 93 |
| Hypertension | Vascular disorders | 2 of 102 | 2 of 94 | 4 of 94 | 2 of 94 | 1 of 90 | 1 of 93 |
Serious events with the highest arm-level rate: hyponatraemia (1.1%), arthritis reactive (1.1%), back pain (1.1%), dizziness (1.1%), gastric cancer (1.1%).
The safety record lists the number at risk and the number affected by serious adverse events for each arm. The serious-event counts are 1 among 102 at risk for 1200 mg once daily; 4 among 94 for 400 mg twice-daily; 4 among 94 for 600 mg twice daily; 2 among 94 for 800 mg once-daily; 1 among 90 for 800 mg twice daily; and 0 among 93 for placebo. These are reported counts, not comparative statistical tests. No relative risks, confidence intervals, or adjusted safety comparisons are reported.
The registry lists Hyponatraemia, Arthritis reactive, Back pain, Dizziness, Gastric cancer, and Haemoptysis among the top serious-event terms, each at 1.1%. It does not connect these terms to particular arms in the posted term list. A serious adverse event is not necessarily caused by the study treatment; the registry data presented do not establish causation.
Deaths are not reported in the registry record. The counts describe the recorded safety data and should not be read as a complete characterization of all possible harms, or as evidence that an event cannot occur. The registry does not provide further detail about event definitions, follow-up duration for safety, or the methods used to collect and assess adverse events.
15. What the Result Does, and Does Not, Mean
The posted primary results describe mean pain-score changes over the trial period. Mean pain decreased in every arm, including placebo. The recalculated mean differences between each eslicarbazepine regimen and placebo are negative, indicating greater estimated average reductions in the active arms. But every recalculated confidence interval includes zero, and none of the unadjusted p-values is below 0.05. Taken together, the posted summary statistics do not establish a clear difference in mean change between any regimen and placebo.
That interpretation is about the average change on the recorded scale. It does not establish whether an individual participant experienced improvement or worsening, how many participants reached a particular level of relief, or how the results affected daily function. The registry does not post responder outcomes or a threshold for a clinically important change. The mean and standard error also do not reveal the full distribution of individual outcomes.
The comparisons are recalculated from arm-level summary statistics using approximate pooled variability. They are not a replacement for the trial’s original analysis, whose full methods are not reported in the registry record. The unadjusted nature of the comparisons also matters because there are several dose-regimen comparisons. Without the original analysis plan, missing-data details, and multiplicity approach, the posted results cannot resolve all questions about how the trial’s primary inference was intended to be made.
Nor do these results settle comparisons among the active regimens. Each posted contrast uses placebo as its comparator; no direct randomized contrast between active dose schedules is reported. Differences in the observed arm means are descriptive and do not, by themselves, prove a dose-response pattern or establish which regimen is preferable.
The appropriate scope is therefore narrow: the registry reports mean pain reductions across all groups and uncertain unadjusted contrasts with placebo. The results do not establish a treatment effect, rule one out, or give medical advice. The absence of a clearly separated contrast in these recalculations should not be interpreted as proof of no effect.
16. Why This Trial Matters Statistically
This trial raises several statistical issues common to multi-arm clinical studies. It compares five dose schedules with one placebo group, making the choice of the primary comparison and the handling of multiple tests important. The registry record identifies the primary endpoint but does not report a multiplicity plan or the original analysis strategy. Readers therefore need to distinguish the posted arm summaries from the unadjusted recalculations for individual comparisons.
The endpoint is a repeated diary-based measure summarized as change in mean pain. Its definition uses a limited set of available ratings near baseline and near treatment completion. That makes the treatment of incomplete diaries and missing endpoint observations relevant to interpretation, yet those methods are not reported in the registry record. The record also does not identify the analysis population behind the outcome results.
The results illustrate why effect estimates and precision belong together. The active arms have more negative mean changes than placebo, but the uncertainty intervals for the recalculated contrasts include zero. A direction that favors one arm in a point estimate is not equivalent to a precise or conclusive difference. Conversely, uncertainty around a contrast does not prove equality. The observed contrast and its interval should be interpreted together, with attention to whether the calculation matches the trial’s intended model.
Finally, the sample-size illustrations show how planning depends on the assumed target effect: planning for a smaller fraction of the observed effect requires more participants per arm under the stated assumptions. Because those calculations start from observed contrasts, they are illustrations rather than evidence about the original design or a future study’s appropriate target. The original sample-size justification is not reported in the registry record. These points make the trial useful for examining endpoint definition, multi-arm inference, uncertainty, and the limits of registry-level summaries.
17. 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 registry record does not report participant eligibility criteria, baseline characteristics, or details of the analysis population. Although overall enrollment is listed, the outcome and safety group counts do not align exactly across the arms, and the record does not explain the differences. Without an analysis-population definition, it is difficult to determine how the posted outcome counts relate to the randomized groups.
The primary outcome depends on diary ratings collected near baseline and the end of treatment. The registry defines which ratings contribute to the means but does not describe incomplete diaries, missing endpoint values, imputation, or sensitivity analyses. The original model specification, covariate adjustment, and diagnostic checks are also not reported. The recalculated contrasts use approximate pooled variability from arm summaries and should be understood as unadjusted estimates rather than a reconstruction of the original analysis.
There are five active-versus-placebo comparisons, but no multiplicity method or testing hierarchy is reported. The posted secondary outcome count is zero, and the record lists zero analysis records. No direct active-arm comparisons are posted. The original sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record.
For safety, the registry lists serious-event counts and selected event terms, but does not report deaths, event attribution to treatment, or further collection and assessment methods. These limitations restrict the questions that can be answered from the registry summaries. They do not show that unreported procedures were absent; they mean that those details are not reported in the registry record.
18. Related Tutorials
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: Efficacy and Safety of Eslicarbazepine Acetate as Therapy for Patients With Post-Herpetic Neuralgia — NCT00981227.
- Registry record last updated 2014-10-29; status last verified 2014-10.
- Results first posted 2013-05-03.
- 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.
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21. Record Summary
The registry describes a completed phase 2 randomized, quadruple-masked, parallel-group, placebo-controlled trial of eslicarbazepine acetate for post-herpetic neuralgia. It records enrollment of 567 and a primary endpoint of mean pain change on the Numeric Rating Pain Scale from baseline to 13 weeks.
Five eslicarbazepine schedules were compared with placebo. Mean pain declined in every arm. Recalculated unadjusted contrasts favor larger mean reductions in the active arms, but each confidence interval includes zero. The registry record does not report the original analysis plan, missing-data methods, or multiplicity strategy, limiting interpretation beyond the posted summaries.