Neuropathic Pain Management: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neuropathic Pain Management (NCT01263132), a randomized phase 3 study. The primary outcome is Mean Neuropathic Pain Score at Visit 3 (Week 1).

2. Clinical Question

The registry describes a randomized, controlled, double-blind, parallel-group Phase 3 trial of treatment for neuropathic pain in people with chronic distal diabetic polyneuropathy. Its stated objective was to assess efficacy, safety and superiority of F0343, described in the brief summary as gabapentin combined with B vitamins, compared with gabapentin alone. The intervention and outcome-arm labels are not fully consistent: the intervention is named F0434, while the posted combination arm is labelled MF0434 + Gabapentin. The registry record does not explain the naming variation.

The primary endpoint is a continuous score, with higher values indicating greater pain intensity. It combines ratings across pain descriptors into a total score. The record also lists a quality-of-life secondary outcome assessed with the Short Form 36 questionnaire. The posted comparison therefore addresses the Week 1 mean score, not every aspect of pain, quality of life, safety, or longer-term outcomes.

3. Trial Design

This was a completed, randomized, double-blind, parallel-group Phase 3 trial with an enrollment of 104. The registry lists February 2008 as the study start and February 2010 as the primary completion. The sponsor was Merck KGaA, Darmstadt, Germany. The listed interventions are F0434 and gabapentin, and the posted primary outcome compares Gabapentin with an arm labelled MF0434 + Gabapentin.

The trial summary describes a prospective, randomized, double-blind, comparative, experimental controlled study intended to assess efficacy, safety and superiority of F0343, described as gabapentin combined with B vitamins, against gabapentin alone. The registry record does not explain why the combination is labelled F0343 in the brief summary, F0434 in the intervention list, and MF0434 in the outcome arm. Those labels are therefore retained as they appear in their respective registry entries rather than treated as interchangeable evidence about the formulation.

The primary result is reported for the Per Protocol population. That population is defined in the record as all participants who were randomized and took at least 1 dose of study medication. The record also states that the Intention to treat and Per Protocol populations were the same. The outcome summaries include 38 participants in the gabapentin arm and 37 in the combination-labelled arm.

There are five outcome measures listed in the record, including the primary pain score and a secondary quality-of-life assessment using the Short Form 36 questionnaire. One secondary outcome is posted. No analysis entries are posted. Details such as the method of sequence generation, concealment of allocation, treatment doses, planned follow-up beyond the stated endpoint, and the original 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: A total of 104 participants were recruited for the study, out of which 29 participants were screen failures which were not randomized and did not receive study treatment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per Protocol (PP) population included all participants who were randomized and took at least 1 dose of study medication. In this clinical study Intention to treat (ITT) and PP populations were the same.

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 Mean Neuropathic Pain Score at Visit 3 (Week 1), measured over Visit 3 (Week 1).

The primary endpoint is the mean neuropathic pain score at Visit 3 (Week 1). The questionnaire covers ten descriptors: intensity, stinging, burning, dull pain, coldness, sensitivity, numbness, depth, superficial, and unpleasant. Each relevant dimension contributes to a total score ranging from 0 to 100. The descriptions of the scoring also refer to ratings from 0 (no symptoms) to 10 (worst symptoms imaginable). A higher total score indicates greater pain intensity.

A continuous score preserves variation across participants rather than reducing the outcome to categories such as improved or not improved. Comparing group means can summarize the average score in each arm at the specified visit. The interpretation is limited to this measure and time point: it does not by itself describe each participant’s experience, the course of pain at other visits, or quality of life.

The endpoint is relevant to the trial’s stated focus on neuropathic pain. However, the registry record does not report a threshold for a clinically meaningful difference, nor does it explain how the individual questionnaire dimensions were combined beyond stating that they generate a total score. The endpoint should therefore be read as a numerical measure of reported pain intensity, with higher scores representing worse intensity, rather than as a direct classification of clinical benefit.

7. Results Posted in the Registry

• MF0434 + Gabapentin: mean 50.70 versus 51.00 on control; difference -0.30 (95% CI -8.01 to 7.41), standardized effect d = -0.02; z-test p = 0.939.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, and the registry reports the mean and standard deviation for each arm. A mean describes the average score within a group. A standard deviation describes how dispersed individual scores are around that group mean; it is not the uncertainty in the mean itself. In this trial, the arm means were 51.0 and 50.7, with standard deviations of 17.39 and 16.67, respectively.

What does a mean difference represent?

The reported mean difference compares the combination-labelled arm with gabapentin. It is -0.3, with negative values indicating a lower average score in the combination-labelled arm under the comparison’s stated direction. Since lower scores indicate less reported pain intensity on this measure, the direction describes the observed contrast. The numerical estimate is not a statement about every participant, and it does not establish that the difference is important in clinical terms. The registry record does not report a threshold for interpreting clinical importance.

How should the confidence interval be read?

A confidence interval expresses uncertainty around an estimated difference. In general, a wider interval indicates less precision because a broader range of values remains compatible with the observed data under the interval procedure. The interval reported for this comparison extends from -8.009 to 7.409. It includes zero and values on both sides of zero. This means the posted estimate is not precise enough to distinguish a small difference from a wider range of possible differences. The registry record does not state the confidence level or give the full interval method, so those details should not be inferred.

What does the p-value say?

The unadjusted p-value is 0.939. A p-value is a measure of how compatible the observed data are with a specified null model, assuming that model and the test’s other assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The record labels this value as unadjusted but does not report the test procedure, its assumptions, or whether any other inferential procedures were planned.

Why does variation matter?

Variation among participant scores affects how precisely group means and their difference can be estimated. When individual scores vary substantially relative to the difference between group means, the comparison may remain uncertain even when the estimated means are close. Here, the reported standard deviations are much larger than the absolute value of the reported mean difference. This is a descriptive comparison of the posted statistics, not a separate test or a newly calculated measure.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model underestimates variation, standard errors can be too small and inferential conclusions can appear more certain than warranted. The posted primary result is summarized by means and standard deviations, and the registry record does not report a model-based analysis or an assessment of over-dispersion. This general issue should not be mistaken for evidence that over-dispersion occurred in this trial.

What is and is not specified about analysis?

The record identifies the Per Protocol population and says it included randomized participants who took at least 1 dose. It further says that the Intention to treat and Per Protocol populations were the same. The posted outcome counts are 38 and 37. The record does not report the statistical test, covariate adjustment, handling of missing outcome values, treatment of protocol deviations, or a prespecified analysis plan. These omissions limit the degree to which the posted summary can be used to reconstruct the analysis.

The record lists five outcome measures, one posted secondary outcome, and zero posted analysis entries. The absence of posted analysis entries does not prove that no analyses were conducted; it means that analysis details are not available in the registry record. Likewise, the registry does not report whether the primary outcome was adjusted for multiple comparisons or whether any interim analyses took place.

General statistical interpretation distinguishes an estimate from the method used to obtain it. The arm means and the mean difference summarize the outcome, while the standard deviations describe observed spread and the confidence interval describes uncertainty in the contrast. The p-value addresses compatibility with a null model. None of these quantities alone establishes clinical importance, confirms the assumptions of an unreported test, or resolves limitations from unreported analysis details.

10. Confidence Intervals and Precision

The estimated mean difference is -0.3 points, comparing the MF0434 + Gabapentin-labelled arm with gabapentin. Its confidence interval extends from -8.009 to 7.409 points. The interval crosses zero, the value corresponding to no mean difference. Its endpoints also allow for possible differences in either direction, rather than concentrating narrowly around the estimate.

Confidence intervals are useful because they show uncertainty around an estimate, not just its direction. In general, a narrower interval means the estimate is more precise, while a wider interval leaves more possible values consistent with the data and the interval method. The reported interval is broad relative to the point estimate. Accordingly, the near-zero difference should not be read as a precise demonstration of no difference.

The arm-level standard deviations, 17.39 and 16.67, indicate appreciable spread in pain scores among participants. The outcome groups contain 38 and 37 participants. Both the amount of score variation and the number of participants contribute to uncertainty in a group comparison. The registry record does not give the confidence level or method used to form this interval, so those features cannot be described more specifically.

The interval is not a range containing a known proportion of individual participant scores, and it is not a prediction interval for a future participant. It pertains to uncertainty in the mean difference. The registry record also does not provide a clinically meaningful threshold against which to judge the interval. Its statistical breadth can be described, but the clinical implications of particular values within it cannot be determined from the posted record alone.

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.

The planning values are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design justification. The assumptions stated for this planning exercise are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 50,638 participants per arm for 80% power and 67,789 participants per arm for 90% power. For planning at 75% of the observed effect, they are 90,022 participants per arm for 80% power and 120,514 participants per arm for 90% power. For planning at 50% of the observed effect, they are 202,549 participants per arm for 80% power and 271,156 participants per arm for 90% power.

In plain terms, the 80% power column gives the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is present. The 90% power column applies the corresponding 90% target. These are design-planning concepts, not probabilities that the observed trial result is correct. Smaller effects require more participants to detect under otherwise unchanged assumptions, as reflected in the increasing planning values when the effect fraction is reduced.

This is not observed power. It is a planning illustration computed from the observed effect, not evidence about the trial’s original recruitment target or its original design choices. The registry record does not report the original sample-size justification or assumptions used to plan enrollment.

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 z_1−α/2 = 1.960) and the desired power (z_1−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

1. Observed difference Δ = -0.300; pooled standard deviation σ = 17.039.
2. n = 2 × (1.96 + 0.842)² × 17.039² / -0.300² = 50,637.2, rounded up to 50,638 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 <- -0.299999999999997                      # observed difference in means
sigma <- 17.0387343169406                     # 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(1263132)
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 = 50,638 (80% power), 67,789 (90% power)
 75% of observed effect: n per arm = 90,022 (80% power), 120,514 (90% power)
 50% of observed effect: n per arm = 202,549 (80% power), 271,156 (90% power)
power.t.test: 50638.2 
Simulated power at n = 50,638 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 lists five outcome measures, including the primary mean neuropathic pain score at Visit 3 (Week 1) and a secondary quality-of-life outcome assessed with the Short Form 36 questionnaire. One secondary outcome is posted, and no analysis entries are posted. Multiple outcomes can raise multiplicity concerns when several hypotheses are tested, because the chance of at least one apparently notable result can increase as more tests are considered. Whether that concern applies in a particular way depends on the prespecified analysis strategy.

The registry record does not report a multiplicity adjustment, a testing hierarchy, or a plan for interpreting secondary outcomes alongside the primary endpoint. It also does not report whether additional outcomes were analyzed but not posted. The reported unadjusted p-value should therefore be understood as unadjusted, rather than assumed to account for testing across outcomes or analyses.

For the primary outcome, the record defines the analysis population as Per Protocol: randomized participants who took at least 1 dose of study medication. It states that the Intention to treat and Per Protocol populations were the same. The posted group summaries contain 38 participants for gabapentin and 37 for the combination-labelled arm, while overall enrollment was 104. The registry does not give a participant disposition account explaining those numbers.

Details of missing-data handling are not reported in the registry record. It is not stated whether any Week 1 scores were missing, how missing observations were handled, whether participants were excluded after randomization, or whether sensitivity analyses were used. The record also does not provide protocol-deviation criteria or an explicit account of how the analysis populations were constructed beyond the stated definition. These omissions make it difficult to assess whether the posted summaries could be affected by missing observations or analysis-population choices.

The registry record does not report interim analyses or a detailed statistical analysis plan. That absence should not be interpreted as evidence that interim analyses or a plan did not exist; the record simply does not report them. As a result, the posted mean comparison can be described, but its relationship to any broader prespecified testing strategy cannot be established.

14. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures report zero affected participants in each arm: zero of 38 in the gabapentin arm and zero of 37 in the MF0434 + Gabapentin-labelled arm. No serious adverse event terms are listed. Death counts are not reported in the registry record.

These figures describe the posted serious adverse event summaries for the outcome groups. They do not establish that no serious events occurred in all enrolled participants or outside the reporting represented by these entries. The record does not provide a detailed definition of the observation period, event collection procedures, or a participant flow account that would explain the relation between the adverse-event counts and total enrollment.

The record also lists other adverse events affecting 22 participants in the gabapentin group and 23 in the combination-labelled group. Those figures are not serious adverse event counts and should not be conflated with them. The registry does not list the individual terms for serious events, and the zero counts should be read as the posted participant counts, not as proof of equal safety between the arms.

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

The posted data show similar Week 1 mean neuropathic pain scores in the two outcome groups: 51.0 for gabapentin and 50.7 for the arm labelled MF0434 + Gabapentin. The estimated mean difference is -0.3, and the unadjusted p-value is 0.939. The confidence interval, from -8.009 to 7.409, includes zero and a range of values on either side. The result therefore does not identify a precise difference between the group means.

That is not the same as proving that the treatments have equal effects. A failure to distinguish the means statistically does not establish equivalence or non-inferiority, particularly when the registry record does not report an equivalence margin, a non-inferiority margin, or an analysis plan for either question. The interval’s breadth leaves uncertainty about the size and direction of a possible difference.

The registry describes the trial as intended to assess efficacy, safety and superiority, but the posted primary result addresses only a specific continuous outcome at Visit 3 (Week 1). It does not establish what happened at other time points or on the Short Form 36 quality-of-life measure. The registry lists one secondary outcome, but no secondary numerical result is included in the stated details.

Nor does the primary result answer every safety question. The posted serious adverse event counts are zero in each group, but death counts are not reported, and other adverse events affected participants in both groups. The available summaries do not establish comparative safety across all possible events or periods.

Overall, the statistics support a cautious description: the recorded Week 1 group averages were close, but the estimated difference is imprecise. The record does not report a clinically meaningful difference threshold, detailed analysis methods, missing-data handling, or the original design rationale. Those gaps restrict stronger conclusions about clinical importance or the broader effects of the interventions.

16. Why This Trial Matters Statistically

This trial illustrates the distinction between an observed point estimate and the information contained in its uncertainty interval. The mean difference is close to zero, but its confidence interval extends across values in both directions. Statistical interpretation should account for that range rather than relying on the point estimate or p-value alone.

The outcome is continuous and includes participant-reported pain descriptors. Means provide a compact summary, while standard deviations show the spread of participant scores. When score variation is substantial relative to the estimated difference, the comparison can be imprecise. The posted results make this issue visible through the combination of close means, sizeable standard deviations, and a broad interval.

The trial also highlights why non-significant evidence is not evidence of equivalence. A conclusion that two treatments are sufficiently similar requires an appropriate margin and analysis; neither is reported in the registry record. A large p-value by itself does not establish that any possible difference is negligible.

Registry interpretation also depends on transparency about populations and analysis choices. Here, the record describes a Per Protocol population and states that it was the same as the Intention to treat population, but the outcome group counts are smaller than overall enrollment. Without participant disposition and missing-data details, readers cannot fully trace how the posted summaries relate to enrollment.

Finally, the intervention labels vary within the registry record, and the record does not explain the differences. That matters for accurate description of what was compared. Together, these features make this trial a useful example of reading a registry result narrowly: identify the outcome, population, time point, estimate and uncertainty, then distinguish what those data support from questions the record does not answer.

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 posted primary outcome is limited to Visit 3 (Week 1). The registry record does not report primary pain-score results at other visits, so the result cannot describe the trajectory of scores over time. The record also lists a quality-of-life secondary outcome but does not include its numerical result in the stated details.

The intervention naming is inconsistent across the registry entries. The brief summary refers to F0343, the intervention listing names F0434, and the posted arm is labelled MF0434 + Gabapentin. The summary describes a combination with B vitamins, but the record does not explain the differing labels. This makes it important to retain the posted arm terminology rather than silently assuming all labels are identical.

Overall enrollment was 104, while the primary outcome summaries include 38 participants in the gabapentin group and 37 in the combination-labelled group. The registry record does not provide a participant flow account that explains the difference, nor does it report missing-data handling or reasons for any unavailable outcomes. Although the record states that the Per Protocol and Intention to treat populations were the same, further details about population construction are not reported.

The registry record does not report treatment doses, allocation concealment, the method of random sequence generation, an original sample-size justification, or detailed analysis methods. It also does not report the confidence level for the interval, a clinically meaningful difference threshold, multiplicity procedures, interim analyses, or a full statistical analysis plan. These omissions limit assessment of the design and analysis beyond the posted summary statistics.

Finally, the serious adverse event entries report no affected participants in either arm, but death counts are not reported. The record does not give detailed safety observation procedures or event terms. Safety interpretation is therefore limited to the posted counts rather than a comprehensive assessment of harms.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Neuropathic Pain Management — NCT01263132.
• Registry record last updated 2014-02-13; status last verified 2014-01.
• Results first posted 2011-10-27.
• 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.

21. Record Summary

NCT01263132 is a completed randomized, double-blind, parallel-group Phase 3 trial titled “Neuropathic Pain Management.” It enrolled 104 participants and compared gabapentin with a combination-labelled arm for neuropathic pain in chronic distal diabetic polyneuropathy. The primary outcome was mean neuropathic pain score at Visit 3 (Week 1), reported for 38 participants receiving gabapentin and 37 receiving MF0434 + Gabapentin.

The means were 51.0 and 50.7, respectively; the posted mean difference was -0.3, with a confidence interval from -8.009 to 7.409 and an unadjusted p-value of 0.939. The interval is broad and includes zero, so the estimate is not precise enough to establish a narrow range of possible differences. The record lists a Short Form 36 quality-of-life outcome, but no numerical result for it is stated. Details of missing-data handling, multiplicity, the original sample-size justification, and the full analysis plan are not reported in the registry record.