Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery (NCT03794388), a randomized phase 3 study. The primary outcome is Change in Neuropathic Pain Score at 2 Months (Numeric Rating Scale 0-10).

2. Clinical Question

The comparison is between two treatment strategies rather than between treatment and no treatment. The reported primary outcome is a numeric pain rating, so the result describes an average score and the uncertainty around the difference between group averages. It does not by itself describe how every participant's pain changed, or how many participants had a particular degree of improvement.

3. Trial Design

The registry record describes a phase 3, randomized, open-label, parallel-group study. It is titled as a multicentric comparison of topical capsaicin at 8% with oral pregabalin for early treatment of neuropathic pain after primary surgery for breast cancer. Masking is listed as none, so the record does not describe a blinded comparison. The study status is completed.

The registry lists enrollment as 140. The primary outcome summaries are reported for 65 participants in the capsaicin group and 51 in the pregabalin group. The record does not explain the relationship between the enrollment figure and the numbers represented in these outcome summaries. The number included in each analysis, the handling of participants without outcome data, and the analysis population are not reported in the registry record.

The capsaicin arm description specifies patches applied to the painful area, with a possible second application 3 months later. The pregabalin arm description gives a starting dose of 50 mg / day in 2 doses, with increases according to tolerance through 100 mg / day and 150 mg / day, up to a maximum dose of 600 mg / day. An interval of 3 to 7 days is described between increases. These are the registry's arm descriptions; details about adherence, treatment changes, and whether each participant followed the stated schedule are not reported in the registry record.

The study start is recorded as 2019-03-19, and primary completion as 2022-11-18. The sponsor is Institut Cancerologie de l'Ouest. The original design assumptions, including the justification for the planned enrollment, are not reported in the registry record. The record also does not report a protocol-level statistical analysis plan or an account of any interim analyses.

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.

Overall Study

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 Change in Neuropathic Pain Score at 2 Months (Numeric Rating Scale 0-10), measured over 2 months.

The primary outcome is titled as change in neuropathic pain score at 2 months and uses the Numeric Rating Scale, an 11-point scale from 0 to 10. A score of 0 indicates no pain, while 10 indicates the worst imaginable pain. Higher scores represent worse pain. A numeric pain scale provides a direct, ordered way to record a participant's reported pain intensity at a specified assessment time.

The posted group summaries give a mean of 4.1 with a standard deviation of 2.5 for capsaicin, based on 65 participants, and a mean of 4.6 with a standard deviation of 2.9 for pregabalin, based on 51 participants. The comparison is expressed as pregabalin minus capsaicin, with an estimated mean difference of 0.5. On a scale where higher scores mean worse pain, a positive difference means the reported average score was higher in the pregabalin group. This direction describes the score contrast only and does not establish a treatment effect.

There is an important reporting detail: although the endpoint title uses the word “change,” the description says the score was collected at 2 months. Baseline scores and the calculation of change are not reported in the registry record. The posted summaries therefore should be interpreted according to the outcome information available, without assuming how any baseline adjustment or change calculation was performed.

7. Results Posted in the Registry

• Arm PREGABALINE: mean 4.60 versus 4.10 on control; difference 0.50 (95% CI -0.50 to 1.50), standardized effect d = 0.19; z-test p = 0.328.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to 6 Months in Neuropathic Pain Score (Numeric Rating Scale 0-10)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Experimental ARM: mean -2.20 versus -2.70 on control; difference 0.50 (95% CI -0.50 to 1.50), standardized effect d = 0.19; z-test p = 0.328.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Experimental ARM and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome: change from baseline to 6 months in the Numeric Rating Scale pain score. The group summaries show negative changes in both arms, which indicates lower scores relative to baseline on a scale where higher scores represent worse pain. The estimated contrast follows the same direction as the primary comparison, while the uncertainty also includes no difference. This provides a broadly similar descriptive pattern across the posted primary and secondary assessments, rather than a clearly separated result at one time and a different result at the other.

The secondary outcome is related to the primary question, but it is not interchangeable with it. The primary outcome is titled as change at 2 months, while its description refers to a score collected at 2 months and does not provide baseline values or the change calculation. The secondary outcome explicitly refers to change from baseline to 6 months. The registry therefore does not provide enough detail to make a direct comparison of change over time or to conclude that the treatment contrast remained constant between assessments.

The registry reports an unadjusted comparison for the secondary outcome and lists no reported analyses. An unadjusted secondary result carries less weight than a prespecified primary result because multiple outcomes or time points can create more opportunities for apparently notable findings. Without a reported multiplicity plan, the chance of false-positive evidence across a set of analyses cannot be assessed. The secondary finding is best treated as supporting descriptive context, not as an independent confirmation of the primary comparison.

The secondary summaries do not establish that a particular participant improved, nor do they show the proportion reaching a meaningful improvement threshold. That threshold, individual response counts, and any formal analysis comparing the two assessment times are not reported in the registry record. The overall pattern is therefore limited to the direction and uncertainty of the posted group-level summaries.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline to 6 Months in Neuropathic Pain Score (Numeric Rating Scale 0-10)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean compare?

General statistical explanation: a mean is the arithmetic average of a set of measured values. Comparing group means gives a concise description of the difference in average outcome between groups. It does not show the full distribution of scores, the number of participants who improved, or whether every participant had a result close to the average. Here, the reported primary group means are 4.1 for capsaicin and 4.6 for pregabalin. The registry identifies the outcome as a continuous measure summarized by a mean and standard deviation.

The standard deviation describes how spread out individual values are around a group mean. It is not the uncertainty in the estimated mean difference. The reported standard deviations are 2.5 and 2.9 for the primary outcome. Greater variation among individuals can make it harder to estimate a group contrast precisely, especially when the number of observations is limited. A group mean and standard deviation alone do not show whether the score distribution is symmetric or contains unusual values.

How should the mean difference be read?

The primary comparison defines the mean difference as the pregabalin group mean minus the capsaicin group mean. Its estimate is 0.5 units. A positive result therefore indicates a higher average score in the pregabalin group, and higher scores represent worse pain on this scale. The direction depends on the stated subtraction order: reversing the order would reverse the sign while describing the same distance between group means. The comparison is unadjusted, so the reported contrast is not described as controlling for baseline scores or other participant characteristics.

General statistical explanation: an unadjusted comparison uses the reported group summaries without accounting for additional variables in a model. Randomization is intended to support a fair comparison of assigned groups, but a registry summary does not reveal whether chance differences in baseline characteristics occurred or how they were handled in analysis. Baseline outcome summaries, an adjusted estimate, and the analysis details are not reported in the registry record.

What does the confidence interval add?

General statistical explanation: a confidence interval gives a range of values that are reasonably compatible with the data under the assumptions of the statistical method. It expresses precision as well as direction. For the primary mean difference, the reported interval has a negative lower limit and an upper limit of 1.501. Since it crosses zero, the data are compatible with no mean difference as well as differences in either direction. The interval is not a range containing a stated proportion of individual participants' pain scores; it concerns the group mean difference.

The interval is more informative than looking only at the point estimate. The estimate of 0.5 is one value, while the interval indicates that uncertainty around it is wide enough to include both a lower score in the pregabalin group relative to capsaicin and a higher score. No threshold for a clinically important mean difference is reported, so the interval cannot be classified against such a threshold using the registry information alone.

What does the p-value say?

General statistical explanation: a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the statistical model were correct. The reported unadjusted p-value for the primary contrast is 0.328. It is not the probability that there is no treatment difference, and it does not measure the probability that the observed estimate occurred “by chance.” Nor does it show whether a difference is important to patients. Read together with the confidence interval, the p-value reflects that the estimate does not sharply distinguish the observed data from a zero mean difference.

The record does not provide a prespecified significance threshold for the primary analysis. A common planning assumption in the sample-size illustration is a two-sided significance level of 0.05, but that is stated as an assumption for that illustration, not as a confirmed original trial analysis rule. The original trial's significance threshold and test procedure are not reported in the registry record.

Why do the method details matter?

General statistical explanation: an analysis plan specifies how outcomes, missing observations, multiple comparisons, and departures from assumptions will be handled. These choices affect how estimates and uncertainty are calculated and how strongly findings can be interpreted. For example, a model that adjusts for a baseline score can target a different estimate from a simple comparison of follow-up means. A method for incomplete outcomes can also affect which observations contribute and what assumptions are needed. The registry record does not report the method used to handle missing primary outcomes, any baseline adjustment, the exact confidence-interval procedure, or a detailed analysis population.

The record lists no reported analyses. The posted primary and secondary comparisons nevertheless include estimates, confidence intervals, and unadjusted p-values. They can be read as the numerical summaries available in the registry, but the absence of a fuller analysis description limits assessment of how they were generated and whether they match a prespecified plan. The record does not indicate an interim analysis, and an interim-analysis plan is not reported in the registry record.

General statistical explanation: variation between individuals is relevant because pain scores can differ substantially even among people receiving the same treatment. Standard deviations describe that observed spread, while confidence intervals describe uncertainty in a group contrast. When variation is large relative to the separation of group means, a study may estimate the difference imprecisely. The mean difference and interval should therefore be considered together rather than treating the p-value as the sole summary.

11. Confidence Intervals and Precision

The estimated primary mean difference is 0.5 units, with pregabalin minus capsaicin as the comparison direction. Its 95% confidence interval has a negative lower limit and an upper limit of 1.501. Because zero lies within the interval, the data do not isolate a difference in one direction. The interval also makes clear that the point estimate should not be treated as an exact or highly precise measure of the contrast.

A confidence interval represents uncertainty about the group-level estimate, conditional on the analysis and its assumptions. It does not describe the range of individual pain scores, and it does not mean that there is a 95% probability that the true difference is inside this particular interval. General statistical explanation: in repeated studies using the same procedure, confidence intervals constructed in this way would cover the fixed true parameter at the stated rate if the method's assumptions were satisfied.

The reported standard deviations of 2.5 and 2.9 indicate variability in the group scores. The group counts contributing to the summaries are 65 and 51. The interval incorporates uncertainty in the comparison; it is not obtained by simply comparing the standard deviations or looking at the overlap of the groups' score distributions. The registry does not report the exact confidence-interval method or whether the primary outcome analysis used adjustment.

Precision and clinical importance are separate questions. An interval can be assessed for precision by its width and whether it includes zero, but judging clinical importance requires a meaningful-difference threshold. Such a threshold is not reported in the registry record. The interval therefore supports a cautious conclusion about uncertainty, not a determination that the possible differences are unimportant.

12. 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 figures are participants per arm, not total event counts. The outcome is continuous, so the illustration gives a required number of participants per arm for each assumed effect and target power. The listed assumptions 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 for 100% of the observed effect, the illustration gives 452 participants per arm for 80% power and 606 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 804 participants per arm for 80% power and 1,076 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 1,808 participants per arm for 80% power and 2,421 participants per arm for 90% power.

In plain language, 80% power means that, under the stated assumptions and if the specified effect were the true effect, the design would have an 80% chance of producing a statistically significant result using the assumed test. The 90% column applies the same idea with a higher target probability. Reaching a higher target power requires more participants for the same assumed effect. Assuming a smaller effect also requires more participants, because a smaller separation between group means is harder to distinguish from random variation.

These figures are a planning illustration based on the observed effect, not observed power. The illustration is not reported as the trial's original sample-size calculation. The original design assumptions and sample-size justification are not reported in the registry record. The displayed planning values should not be read as evidence that the completed study had the indicated power or that a result is valid because it matches one of these scenarios.

13. 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 = 0.500; pooled standard deviation σ = 2.683.
2. n = 2 × (1.96 + 0.842)² × 2.683² / 0.500² = 451.9, rounded up to 452 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 <- 0.5                      # observed difference in means
sigma <- 2.6827911624002                     # 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(3794388)
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 = 452 (80% power), 606 (90% power)
 75% of observed effect: n per arm = 804 (80% power), 1,076 (90% power)
 50% of observed effect: n per arm = 1,808 (80% power), 2,421 (90% power)
power.t.test: 452.9 
Simulated power at n = 452 per arm: 0.795 (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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or assessment times are examined. General statistical explanation: the more tests considered, the greater the opportunity for at least one result to appear statistically notable even when the underlying effects are absent. Prespecified primary outcomes and an analysis plan help distinguish the central question from secondary or exploratory analyses. When multiple tests are planned, methods such as adjustment or a hierarchy of hypotheses can control how the results are interpreted.

The registry lists a primary pain outcome at 2 months and a secondary pain-change outcome at 6 months. It reports no analyses in the analysis listing, and the multiplicity strategy is not reported in the registry record. It is therefore not possible to determine whether any adjustment was planned or performed, whether additional outcomes were analyzed but not posted, or how the primary and secondary findings were prioritized in the trial's original analysis plan. The unadjusted p-values should be understood as unadjusted rather than as results corrected for multiple testing.

Missing-data information is also limited. The posted primary summaries include 65 participants in the capsaicin group and 51 in the pregabalin group, while enrollment is listed as 140. The record does not describe why these figures differ, how many participants had missing outcomes, whether withdrawals occurred, or what methods were used for missing observations. It does not report whether the analysis included all randomized participants, only those with observed measurements, or another analysis population.

General statistical explanation: missing outcomes can affect an estimate if the participants without measurements differ in relevant ways from those with measurements. The consequences depend on why data are missing and the method used to address them. Without a missing-data description or sensitivity analyses, the impact cannot be evaluated from the registry record.

The handling of baseline measurements, protocol deviations, treatment discontinuation, and adherence is not reported in the registry record. These omissions limit assessment of whether the posted summaries represent the randomized comparison as planned. They do not establish that the analyses were incorrect; they mean that the relevant methods and checks cannot be evaluated from the information recorded.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 65 participants at risk in the capsaicin group and zero among 51 participants at risk in the pregabalin group. Deaths are reported as 0 in each group. No serious adverse-event terms are listed. These entries describe the serious-event counts recorded for the groups; they do not establish that no adverse experiences of any kind occurred.

Serious adverse events are a specific category, distinct from all other adverse events. The registry's serious-event figures should therefore be read separately from any non-serious adverse-event reporting. The record does not give further detail on the nature of adverse experiences, event timing, severity grading for non-serious events, relationship to treatment, or how adverse events were collected. Those details are not reported in the registry record.

A zero count in a group is a descriptive observation, not proof that an event cannot occur or that two treatments have identical safety profiles. The posted figures also do not provide a statistical comparison or an uncertainty interval for serious-event risk. They are limited to the serious-event counts and deaths recorded in the registry.

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

The posted primary result describes a modest point difference in average pain scores at 2 months, with a mean of 4.1 in the capsaicin group and 4.6 in the pregabalin group. The estimated mean difference is 0.5 units, defined as pregabalin minus capsaicin. Since higher scores indicate worse pain, the estimate points toward a higher average score in the pregabalin group. The confidence interval extends across zero, and the unadjusted p-value is 0.328. Taken together, these statistics leave substantial uncertainty about the direction and size of the group difference.

This does not show that the treatments are equivalent. Equivalence requires a prespecified margin defining differences small enough to count as practically equivalent, together with an analysis designed to test that question. The registry record does not report an equivalence margin or such an analysis. Nor does the result establish that either treatment does or does not work: the posted comparison is between active treatment groups, and the information reported does not estimate either treatment against no treatment.

The average score is a group-level summary. It does not indicate the number of participants who had a meaningful improvement, the number whose pain worsened, or the distribution of individual responses. No responder threshold or such counts are reported in the registry record. The primary outcome's wording also leaves a reporting ambiguity: it is titled as a change at 2 months, while the description says the score was collected at 2 months. Baseline results and the change calculation are not reported.

The secondary outcome supplies a 6-month change measure, but its unadjusted estimate also remains uncertain and does not resolve the primary finding. A consistent pattern across summaries can be useful context, but it does not replace a clear analysis plan or establish a difference between groups. The result should be understood as a registry-level estimate with limits in precision and reporting detail, not as a definitive ranking of the treatments.

17. Why This Trial Matters Statistically

This trial addresses a focused statistical comparison: two different treatment routes for neuropathic pain after breast cancer surgery, assessed using a patient-reported pain scale. Randomization is important because it is intended to reduce systematic differences between assigned groups and make a treatment comparison more interpretable. At the same time, the open-label design means participants and treatment providers were not masked according to the registry record. The record does not explain whether outcome assessors were masked.

The example also shows why a point estimate cannot be read alone. The primary mean difference is 0.5 units, but its confidence interval crosses zero and extends to values on either side. The p-value of 0.328 similarly does not supply a measure of clinical importance or establish equivalence. Reporting the estimate together with its uncertainty gives a more complete account than describing the finding only as significant or not significant.

Statistically, the trial also illustrates the difference between the number enrolled and the numbers represented in outcome summaries. Enrollment is listed as 140, while the primary summaries have group counts of 65 and 51. The registry record does not explain this relationship, so readers cannot assess the reasons for the available analysis counts or the potential effect of missing outcomes.

Finally, the planning illustration makes clear that sample-size requirements depend on the effect a study is designed to detect and the chosen power target. Its figures are not the original design justification and are not observed power. The original assumptions are not reported in the registry record. These distinctions matter when interpreting an uncertain estimate: a nonsignificant result alone cannot show whether the study was designed to detect a clinically meaningful difference.

18. 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.

Several trial-specific reporting limitations affect interpretation. The primary outcome title describes change in pain score at 2 months, but its description says the pain score was collected at 2 months. Baseline group scores and the method used to calculate change are not reported in the registry record. This makes it difficult to establish whether the posted values should be understood as follow-up scores, changes, or another summary.

The registry gives enrollment as 140 but reports primary outcome summaries for 65 participants in the capsaicin arm and 51 in the pregabalin arm. It does not explain the difference between the enrollment figure and those analysis counts. Participant flow, exclusions, withdrawals, missing observations, and the analysis population are not reported. The posted group summaries therefore cannot be used to infer why particular outcome data are represented or absent.

The record describes the study as randomized, open-label, and parallel group, but does not provide details of sequence generation or allocation concealment. It also does not report baseline characteristics, adherence, treatment discontinuation, or treatment received after assignment. As a result, the registry summary does not allow assessment of group comparability at baseline or of how closely the stated treatment schedules were followed.

The outcome data are limited to group means and standard deviations, without individual-level distributions or responder counts. A clinically important difference threshold is not reported. The registry also does not describe multiplicity control, missing-data methods, covariate adjustment, or a detailed statistical analysis plan. These gaps constrain evaluation of the analysis and its robustness; they do not by themselves demonstrate that the trial was conducted improperly.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery — NCT03794388.
• Registry record last updated 2026-05-05; status last verified 2026-03.
• Results first posted 2026-05-05.
• 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.

22. Record Summary

The registry record describes a completed, phase 3, randomized, open-label, parallel-group comparison of topical capsaicin patches at 8% and oral pregabalin for neuropathic pain after primary breast cancer surgery. Enrollment is listed as 140. The primary outcome is a pain score on a 0-to-10 Numeric Rating Scale at 2 months, with higher scores representing worse pain.

The posted primary means are 4.1 for capsaicin and 4.6 for pregabalin, with an estimated mean difference of 0.5 for pregabalin minus capsaicin. The confidence interval includes zero, and the unadjusted p-value is 0.328. The registry also posts a 6-month change outcome and serious adverse-event counts of zero in each group. Important analysis details, including the original sample-size assumptions, missing-data handling, analysis populations, and multiplicity approach, are not reported in the registry record.