PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy (NCT05246670), a randomized phase 2 study. The primary outcome is Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score.

2. Clinical Question

3. Trial Design

The registry describes NCT05246670 as a randomized, double-blind, parallel phase II pilot trial. Its official title identifies the study as treatment of established chemotherapy-induced neuropathy with N-palmitoylethanolamide, a cannabimimetic nutraceutical. Enrollment is listed as 88. The registry status is active, not recruiting. The recorded start date is 2022-05-16, and the primary completion date is 2024-02-12.

Four arms are described: lower-dose PEA, higher-dose PEA, once-daily placebo, and twice-daily placebo. Each regimen is described as lasting 8 weeks, with the PEA regimens conditional on there being no unacceptable toxicity. The primary outcome comparisons use a combined placebo group, rather than presenting separate primary comparisons against each placebo schedule. Random assignment and double masking are part of the recorded design; further details about how assignment or masking were implemented are not reported in the registry record.

The primary outcome is mean change in CIPN20 score at 8 weeks. The analysis description says the score is recorded at each time point, change from baseline is calculated, and means, standard deviations, and medians with ranges are calculated by PEA arm and for combined placebo. It further describes estimating the difference in change scores between each PEA arm and combined placebo with a 95% confidence interval. Participants who stop protocol treatment before 8 weeks are assigned a change based on their final observation, according to the outcome description.

The record lists adverse events and quality of life among secondary outcomes. The posted numerical results include mean change in quality of life, while numerical results for the listed grade 3+ adverse-event outcome are not reported in the registry record. The record does not report further details of the trial's original sample-size justification, allocation procedure, or full statistical analysis plan.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All evaluable participants were included in analysis

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 Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score, measured over 8 weeks.

The primary endpoint is mean change in the Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 score, or CIPN20, from baseline to 8 weeks. This measure asks participants to rate their experience of symptoms using 20 items. Each item is scored from 1, indicating no difficulty, to 4, indicating the most difficulty, and the responses are summed to a total score from 20 to 80. On that scale, a higher score corresponds to more reported difficulty across the items.

Change from baseline is used to describe how the score differs at follow-up relative to each participant's starting score. The group mean change gives an average summary, while the standard deviation describes how spread out individual changes are around that average. The registry's stated comparison is the difference in mean change between each PEA arm and the combined placebo group. A confidence interval around that difference describes the range of values compatible with the estimate under the analysis assumptions.

The outcome description says the score is summarized at each time point and that the analysis uses eligible randomized participants who initiated treatment and completed the baseline questionnaire. For participants stopping protocol treatment before 8 weeks, their final observation is used to calculate change. The registry does not report additional information about how the score was validated for this trial population or how any other missing questionnaire responses were handled.

7. Results Posted in the Registry

• Lower-dose PEA: mean -4.20 versus -6.40 on control; difference 2.20 (95% CI -1.25 to 5.65), standardized effect d = 0.34; z-test p = 0.211.
• Higher-dose PEA: mean -6.30 versus -6.40 on control; difference 0.10 (95% CI -5.09 to 5.29), standardized effect d = 0.01; z-test p = 0.970.

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.

Mean Change of Quality of Life

• 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:
  • Lower-dose PEA: mean 0.60 versus -0.60 on control; difference 1.20 (95% CI -0.04 to 2.44), standardized effect d = 0.51; z-test p = 0.058.
  • Higher-dose PEA: mean 0.60 versus -0.60 on control; difference 1.20 (95% CI -0.01 to 2.41), standardized effect d = 0.51; z-test p = 0.051.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lower-dose PEA and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Higher-dose PEA and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes listed in the registry include mean change in quality of life and the number of participants experiencing grade 3+ adverse events. The posted numerical secondary results cover mean change in quality of life at 8 weeks. The numerical results for the grade 3+ adverse-event outcome are not reported in the registry record. The quality-of-life comparisons show a directionally similar pattern across the two PEA schedules relative to combined placebo, but their estimates are also uncertain. This broad pattern does not resolve the uncertainty in the primary CIPN20 comparisons.

Quality of life is a separate outcome from the primary CIPN20 score. A secondary measure can add context about participants' experience, but it does not replace the prespecified primary outcome or change what the primary comparison estimates. Agreement or disagreement across measures may reflect differences in what they measure, their variability, and the amount of information available. The registry record does not give enough detail to assess whether the secondary measure was intended to confirm the primary finding or to explore other aspects of outcome.

Unadjusted secondary results carry less weight when several outcomes or comparisons are examined because the chance of observing an apparently notable result through random variation increases as analyses accumulate. A multiplicity adjustment can address some of this issue, but no such adjustment is reported in the registry record. The record lists multiple outcome measures and analyses, but it does not describe a hierarchy, a correction method, or which secondary outcomes were designated confirmatory. The secondary estimates should therefore be treated as exploratory evidence, not as independent confirmation of a treatment effect.

The adverse-event information is reported separately from the quality-of-life outcome. Serious adverse events and grade 3+ adverse events are not automatically the same classification, and the posted serious-event counts should not be substituted for the missing numerical results of the listed grade 3+ endpoint. The distinction matters when interpreting the safety information alongside secondary efficacy-related outcomes.

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

• Number of Participants Experiencing Grade 3+ Adverse Events
• Mean Change of Quality of Life

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: it is a numerical score, and the registry reports its mean and standard deviation. For this kind of outcome, a mean summarizes the average score change in a group. A standard deviation describes the spread of participant-level changes; it is not a confidence interval and does not directly describe uncertainty in the group mean or in the comparison between groups.

What does the mean difference represent?

The comparison is the difference between the PEA group's mean change and the combined placebo group's mean change. A value near zero indicates that the two observed group means changed by similar amounts. A positive or negative value indicates the direction of the difference under the comparison's stated group ordering. The difference is an estimate, not a known fixed treatment effect. In a randomized trial, random variation can make the observed group difference depart from the underlying difference the trial is intended to estimate.

The posted recalculations are identified as unadjusted re-calculations from summary statistics. They use the posted group means, standard deviations, and group sizes to estimate the mean difference and its uncertainty without an adjustment for other variables. An adjusted analysis can use a model or baseline covariates and need not produce exactly the same estimate or interval. The registry record does not report the method used for the sponsor's analyses.

Why does a confidence interval matter?

A confidence interval conveys the precision of an estimate by giving a range of values compatible with the data and the procedure's assumptions. It is not a list of all plausible values in a literal sense, and it does not measure the probability that the particular interval contains the true value. A wide interval means that the estimate is not very precise; a narrow interval indicates greater precision. For the posted primary comparisons, the intervals include zero and extend across values in both directions. The data therefore do not pin down the direction or size of the between-group difference with precision.

A p-value is a measure of how unusual results at least as incompatible with a specified null hypothesis would be if that null hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The recalculated unadjusted p-values accompany the recalculated comparisons. The registry's reported analyses do not include p-values. Because these are unadjusted calculations and the record does not describe a multiplicity procedure, the p-values should not be treated as a complete account of all inferential decisions in the trial.

What does over-dispersion mean for a continuous outcome?

In general, over-dispersion means that observed variation is greater than a model's assumptions allow. That can make standard errors too small and intervals too narrow if the model does not account for the extra variation. For a continuous endpoint, the spread of participant measurements matters because it affects the precision of a group mean and a mean difference. The registry reports standard deviations for the groups, but it does not report an over-dispersion assessment or a model-based adjustment. The recalculation is based on the posted summary statistics and does not establish whether any more complex model would be appropriate.

The outcome description says participants stopping treatment before 8 weeks are evaluated using their final observation. This is a specific rule for early discontinuation described for the primary measure. It does not, by itself, explain how all missing questionnaire data were handled, whether any other imputation was used, or whether sensitivity analyses assessed alternative assumptions. Those details are not reported in the registry record.

How should sample-size planning estimates be understood?

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between the two compared arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. For continuous outcomes in these calculations, the figures are participants per arm. The calculations are planning illustrations based on observed results, not a report of the trial's original design assumptions. The registry record does not report the original sample-size justification or the assumptions used for the trial's own planning.

In general, a power target describes the probability that a study would identify an effect of a specified size under the assumptions used for planning. The 80% and 90% columns show the required per-arm participant count for those respective planning targets, given the stated effect and assumptions. A higher power target requires more participants under otherwise identical assumptions. Smaller effects are harder to distinguish from random variation and therefore require more participants. These planning figures should be viewed alongside the uncertainty in the observed effect, rather than as confirmation that the trial had adequate power.

11. Confidence Intervals and Precision

The primary recalculated comparisons have broad 95% confidence intervals. For lower-dose PEA versus combined placebo, the estimate is 2.2 units and the interval runs from -1.249 to 5.649. For higher-dose PEA versus combined placebo, the estimate is 0.1 units and the interval runs from -5.087 to 5.287. Each interval includes zero and includes both negative and positive differences. The estimates consequently do not precisely establish the direction or magnitude of a difference.

Precision depends on the amount of information in the data, including the number of participants with outcome information and the variability of their scores. The posted primary group sizes are 27 for lower-dose PEA, 30 for higher-dose PEA, and 28 for combined placebo. The standard deviations are 5.42, 12.24, and 7.5, respectively. The higher-dose group has a more dispersed posted score change than the other groups, which contributes to uncertainty in that comparison. In general, greater variation makes it harder to estimate a mean difference precisely when other factors remain similar.

The registry's own analyses report 95% confidence intervals from -1.33 to 5.74 for lower-dose PEA versus combined placebo and from -5.23 to 5.41 for higher-dose PEA versus combined placebo. Those intervals also include zero and are broad. Their estimates are reported as mean differences in final values; the recalculated figures use the posted group summary statistics. The interval descriptions are therefore not interchangeable without regard to the analysis being represented.

Confidence intervals address statistical precision, not clinical importance. The registry record does not report a threshold for a clinically important CIPN20 difference, so it is not possible to use these intervals to decide whether every value they contain would matter to participants. Nor does an interval containing zero prove that the groups are equivalent. That conclusion would require a defined equivalence or non-inferiority framework, which is not reported in the registry record.

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 sample-size illustrations express the estimated number of participants needed for planning comparisons between two groups. Because the outcome is continuous, the displayed figures are participants per arm, not total events. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each calculation targets a stated fraction of the observed effect. The registry record does not report the assumptions underlying the trial's own original sample-size design.

The 80% power column indicates the per-arm participant count estimated to give an 80% chance of detecting the effect specified for that planning scenario, if the calculation's assumptions hold. The 90% power column gives the corresponding count for a 90% target. These are planning probabilities under assumptions, not guarantees about what a future study will find. A more demanding power target generally requires a larger sample, and smaller target effects require more participants because they are harder to distinguish from random variation.

The scenarios use the observed effect as a reference and also consider 75% and 50% of that observed effect. That makes the estimates sensitive to the observed effect size: when the observed difference is very small, the calculated sample requirements can be extremely large. This is particularly apparent for the higher-dose primary comparison, where the recalculated observed difference is 0.1 units. The very large figures in that scenario should be understood as a consequence of planning around a tiny observed estimate, not as a recommendation or as proof that such a difference is the right target.

These figures are planning illustrations, not observed power. Observed power is not a substitute for interpreting the estimated difference and its confidence interval. The trial's original planning rationale, including any target effect chosen before enrollment, is not reported in the registry record.

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 = 2.200; pooled standard deviation σ = 6.563.
2. n = 2 × (1.96 + 0.842)² × 6.563² / 2.200² = 139.7, rounded up to 140 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 <- 2.2                      # observed difference in means
sigma <- 6.56252424973058                     # 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(5246670)
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 = 140 (80% power), 187 (90% power)
 75% of observed effect: n per arm = 249 (80% power), 333 (90% power)
 50% of observed effect: n per arm = 559 (80% power), 748 (90% power)
power.t.test: 140.6 
Simulated power at n = 140 per arm: 0.797 (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. Analyses Reported by the Sponsor

The registry reports the sponsor's own primary comparisons as mean differences in final values. For lower-dose PEA versus combined placebo, the reported estimate is 2.21, with a 95% confidence interval from -1.33 to 5.74. For higher-dose PEA versus combined placebo, the estimate is 0.09, with a 95% confidence interval from -5.23 to 5.41. Both intervals include zero and cover differences in either direction.

The unadjusted recalculations use the posted group means, standard deviations, and sample sizes. They estimate differences of 2.2 and 0.1, with 95% confidence intervals from -1.249 to 5.649 and from -5.087 to 5.287, respectively. The estimates are numerically close to the sponsor-reported estimates, while the confidence limits differ. The record labels the sponsor analyses as comparisons of final values, while the outcome description says the primary analysis estimates differences in change scores. This distinction in description should be kept in mind when comparing the two sets of numbers.

The recalculations are simple, unadjusted calculations from posted summary statistics; they do not recreate an analysis whose method is not described in the record. The registry does not report the method behind the sponsor's comparisons or p-values for those comparisons. The sponsor's reported results and the recalculated summary-statistic results are therefore best read as distinct analyses, rather than treating one as a correction of the other.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study makes several statistical comparisons or evaluates multiple outcomes. Even if each individual test uses the same nominal threshold, examining many results increases the chance that at least one will appear notable through random variation. This is a general statistical concern, not evidence that any particular result in this trial is spurious.

The registry lists a primary outcome, secondary outcomes, 11 outcome measures, and 3 analyses. The posted primary comparisons include each PEA schedule against combined placebo, and the sponsor also reports a comparison between the two PEA arms. The registry record does not report whether the trial used a multiplicity adjustment, a testing hierarchy, a designated family of hypotheses, or a plan for interpreting secondary results. The reported p-values for the recalculations are unadjusted. Without a reported plan, those values should not be interpreted as controlling the overall false-positive risk across all outcomes and comparisons.

Information about missing data is also limited. For the primary measure, the record says the analysis dataset includes eligible randomized participants who initiated treatment and completed the baseline questionnaire. It says that a participant who stops protocol treatment before 8 weeks has a change calculated using the final observation. This describes one approach to early treatment discontinuation, but it does not fully specify how missing follow-up questionnaires, incomplete item responses, or other missing measurements were handled.

The registry record does not report sensitivity analyses under alternative missing-data assumptions, an imputation method, or details about participants excluded from the evaluable analysis. The planned enrollment is listed as 88, while the posted primary arm sizes are reported separately as 27, 30, and 28. Those figures do not by themselves explain all stages of participant flow or the reasons participants may not appear in the primary analysis.

Analysis populations require similar care. The record describes the primary analysis population in terms of eligibility, randomization, treatment initiation, and baseline questionnaire completion, and also states that all evaluable participants were included. It does not report a full intention-to-treat analysis population definition or explain whether the sponsor's analysis used the same population as the posted summary statistics. These omissions limit assessment of how missingness, treatment discontinuation, and analysis-population selection may affect the estimates.

16. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lower gastrointestinal hemorrhage (7.1%), superior vena cava syndrome (7.1%), dizziness (3.4%), infections and infestations - other, specify (3.4%).

The serious adverse-event figures are presented by four assigned groups. In lower-dose PEA, 2 of 29 participants at risk are listed as having a serious adverse event; in higher-dose PEA, 0 of 30 are listed. In once-daily placebo, 2 of 14 are listed, and in twice-daily placebo, 0 of 15 are listed. Deaths are recorded as 0 in each group. These counts describe the registry's reported serious adverse-event information and should be read in light of the group sizes.

The registry also lists serious-event terms with percentages, including lower gastrointestinal hemorrhage and superior vena cava syndrome at 7.1% each, and dizziness and infections and infestations - Other, specify at 3.4% each. The record excerpt does not provide enough detail to infer causation from these terms or to establish whether a particular event was related to study treatment. The listed percentages should not be interpreted as comparative risks without the relevant event definitions and analysis context.

Serious adverse events are distinct from the listed secondary outcome of grade 3+ adverse events. Numerical results for that secondary endpoint are not reported in the registry record. The posted serious-event counts alone therefore do not provide a complete account of all adverse events or of their severity distribution.

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

The posted results describe mean CIPN20 changes over 8 weeks in two PEA dosing groups and a combined placebo group. The recalculated between-group estimates are close to zero for higher-dose PEA and more positive for lower-dose PEA, but both 95% confidence intervals include zero and span differences in either direction. The registry's own reported comparisons likewise have intervals that include zero. The evidence in this record does not precisely determine whether the average change differed between either PEA schedule and placebo.

That interpretation is narrower than saying the treatments have no effect. A non-significant or uncertain comparison does not demonstrate absence of an effect; it means the observed data do not give a precise distinction from zero under the analysis presented. Conversely, the observed mean changes within groups do not establish that a change was caused by the assigned regimen. Changes can reflect multiple influences, and the between-group comparison is the relevant estimate for assessing relative change.

The result also does not establish equivalence. Equivalence requires a prespecified range of differences considered sufficiently small, along with an analysis designed to assess whether the interval lies within that range. No such margin or framework is reported in the registry record. Statistical uncertainty should also be separated from clinical importance: the record does not report a clinically important difference threshold for CIPN20.

The trial is a phase II pilot study with an enrollment listing of 88 and smaller posted analysis groups for the primary outcome. The estimates can inform the range and variability of results observed in this trial, but their precision is limited. The planning illustrations based on observed effects are not evidence that the original trial had a particular power or that a future trial must use those exact sample sizes.

The safety figures are descriptive. They include serious adverse events and deaths by group, but do not establish whether reported events were caused by PEA or placebo. Numerical results for the listed grade 3+ adverse-event secondary endpoint are not reported. Taken together, the record supports a cautious reading of the posted outcome summaries without a definitive claim about benefit, lack of benefit, or comparative safety.

18. Why This Trial Matters Statistically

This trial illustrates why an observed mean change and a between-group treatment comparison answer different questions. The group means describe change within each assigned group, while the primary comparison asks whether the change differed between a PEA schedule and combined placebo. A visible change in one group alone is not evidence of a treatment-specific difference.

It also illustrates the importance of uncertainty. The primary estimates are accompanied by confidence intervals that cover zero and extend in both directions. The point estimates alone could give an overly definite impression; the intervals show that the data are compatible with a range of possible differences. Small outcome groups and variable scores contribute to limited precision, particularly in the higher-dose comparison.

The record offers a useful distinction between sponsor-reported analyses and unadjusted recalculations from group summary statistics. Their estimates are numerically close, but the registry describes the sponsor results as differences in final values and describes the primary estimand as differences in change. The methods behind the sponsor's analyses are not reported. Readers should therefore avoid treating different analysis descriptions as if they were necessarily identical.

Finally, the planning illustrations make clear how sensitive sample-size estimates can be to the effect chosen for detection. A very small observed difference leads to very large calculated requirements when the target is a fraction of that estimate. Such calculations are useful for understanding planning trade-offs, but they are not a substitute for a prespecified target effect, a design justification, or a transparent statistical plan. Those original design details are not reported in the registry record.

19. 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 record leaves important details of the analysis unclear. Although the primary outcome description refers to changes from baseline, the sponsor analyses are labeled comparisons of final values. The registry does not report the sponsor's statistical method, so the relationship between those analyses and the stated change-score approach cannot be fully assessed. The unadjusted recalculations use the posted summary statistics and should not be treated as a reproduction of an undocumented model.

The primary analysis population is described as eligible randomized participants who initiated treatment and completed the baseline questionnaire, with final observation used for those stopping protocol treatment before 8 weeks. A full participant-flow account, detailed missing-data approach, and sensitivity analyses are not reported in the registry record. The enrollment listing and posted outcome group sizes alone do not explain which participants were absent from each analysis or why.

The record does not report the trial's original sample-size justification, the target effect used for design, or the assumptions behind its planned power. The planning illustrations available for interpretation are recalculations based on observed effects and should not be mistaken for that original design rationale. Nor does the record describe a multiplicity strategy across the many outcomes and analyses listed.

The trial is identified as a phase II pilot, and the primary outcome groups are relatively small. The confidence intervals reflect substantial uncertainty, and the higher-dose group has a larger posted standard deviation than the other primary groups. The registry does not state a threshold for a clinically important CIPN20 difference, limiting interpretation of the clinical relevance of values within the intervals.

Safety information is also incomplete for broad comparisons: the record posts serious-event counts and selected terms, but numerical results for the listed grade 3+ adverse-event outcome are not reported. Causal attribution and fuller adverse-event context are not established by the listed counts alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy — NCT05246670.
• Registry record last updated 2025-09-22; status last verified 2025-09.
• Results first posted 2025-01-24.
• 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.

23. Record Summary

NCT05246670 is a randomized, double-blind, parallel phase II pilot trial of PEA for established chemotherapy-induced peripheral neuropathy. The registry lists enrollment of 88 and four arms: lower-dose PEA, higher-dose PEA, once-daily placebo, and twice-daily placebo. The primary endpoint is mean change in CIPN20 score at 8 weeks, with the placebo arms combined for the posted primary comparisons.

The recalculated unadjusted mean differences are 2.2 for lower-dose PEA versus placebo and 0.1 for higher-dose PEA versus placebo. Both corresponding 95% confidence intervals include zero and span values in either direction. The sponsor's reported final-value comparisons also have confidence intervals that include zero. The record includes quality-of-life change as a secondary result and serious adverse-event counts, but does not report numerical results for the listed grade 3+ adverse-event endpoint. Important details about the original sample-size rationale, multiplicity, and some missing-data procedures are not reported in the registry record.