Topical Menthol for the Treatment of Chemotherapy Induced Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Menthol for the Treatment of Chemotherapy Induced Peripheral Neuropathy (NCT01855607), a randomized phase 2 study. The primary outcome is Change in Brief Pain Inventory-Short Form Score.

2. Clinical Question

3. Trial Design

This was a Phase II trial registered as a randomized, placebo-controlled study of topical menthol for chemotherapy-induced peripheral neuropathy. The record lists triple masking and two interventions: topical menthol and placebo lotion. Its stated primary objective was to assess six-week treatment, using twice daily application, among patients receiving or having received chemotherapy for breast, gastrointestinal, or gynecologic cancer. The brief summary specifies taxane- or platinum-based regimens. The trial was sponsored by Columbia University.

The registry lists enrollment of 12 and a start date of 2013-08, with primary completion in 2016-11. The study status is terminated. The primary outcome record attributes termination to poor enrollment and states that no data was collected from participants. It also says participants were not randomized, so results are reported as a combined total and cannot be presented per arm. Thus the listed randomized, masked design describes the intended comparison, while the posted outcome record does not contain a completed randomized comparison.

Secondary objectives included changes in patient-reported measures, dose delivery and early treatment discontinuation, quantitative neurosensory testing, and an exploratory evaluation of whether treatment effects interacted with chemotherapy type. Secondary outcomes listed include change in EORTC-CIPN20 score and change in sensorimotor function. The registry lists 3 outcome measures, but no analyses are reported. Further details of allocation procedures, masking implementation, protocol deviations, recruitment by arm, and reasons for the enrollment difficulty beyond poor enrollment 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: The study was terminated before randomization could be assigned, therefore all participant data is presented as a combined total and cannot be presented per Arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The study was terminated due to poor enrollment; no data was collected from participants. Participants were not randomized, therefore results are reported as a combined total and cannot be presented per Arm.

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.

Population: The study was terminated before randomization could be assigned, therefore all participant data is presented as a combined total and cannot be presented per Arm. 12 participants were enrolled, and 1 withdrew consent, therefore 11 participants are presented in the Baseline Analysis.

6. Primary Endpoint

The registry lists the primary outcome as Change in Brief Pain Inventory-Short Form Score, measured over Baseline and 6 weeks.

The primary endpoint was change in the Brief Pain Inventory-Short Form (BPI-SF) score, assessed at baseline and 6 weeks. The brief summary identifies worst pain score as the measure used to address the primary objective. The BPI-SF is described in the registry as a validated tool for assessing pain severity and its effect on daily functions in people with neuropathy. It includes ratings of pain intensity and severity, as well as pain interference with activity, mood, sleep, relationships with others, and work.

The questionnaire uses a 0-10 scale, with higher scores indicating a worse outcome. A change from baseline is intended to describe how the reported score shifts over the treatment period. Comparing change between the menthol and placebo groups would address the stated treatment question more directly than describing either group alone, because a comparative estimate accounts for change in both groups. However, the record reports no collected participant data and no endpoint results. It provides no observed score change, between-group estimate, measure of precision, or test result. The endpoint’s clinical role can therefore be described, but its result cannot be interpreted for this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can only be assessed to the extent that they are described in the registry record. The intended design was a randomized, placebo-controlled, triple-masked Phase II trial, but the primary outcome record states that participants were not randomized and no participant data were collected. No analysis of the planned treatment comparison is reported. The registry record does not report a statistical analysis plan, an estimation method, a model for repeated measures, or a method for handling incomplete outcomes.

What would a treatment contrast represent?

For the planned primary question, the relevant quantity would be the difference in BPI-SF change between the menthol and placebo groups from baseline to 6 weeks. A group-specific change describes movement within that group; a between-group contrast asks whether the movement differed between assigned treatments. The latter is the quantity aligned with the comparative objective. Here, neither group-specific changes nor a between-group contrast are reported, so no treatment effect can be interpreted.

In general, an effect estimate is more informative when accompanied by an interval describing its uncertainty. A confidence interval gives a range of values compatible with the observed data and the method’s assumptions. A narrow interval indicates greater precision than a wide interval; an interval spanning values that would have different practical interpretations may leave the result inconclusive. These are general statistical principles, not reported analyses for this trial. The registry record contains no estimate or confidence interval for the primary endpoint.

What does the significance threshold mean?

The sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. In general, a significance level is a preselected rule for assessing how unusual data would be under a specified null hypothesis. A two-sided approach considers departures in either direction. It does not measure the probability that a treatment effect is real, and it does not describe the size or clinical importance of an effect. The registry record does not report whether these assumptions were part of the trial’s own protocol or analysis plan; the assumptions are identified as belonging to a planning illustration, not the trial’s design.

The sample-size illustrations are described as based on fractions of an observed effect. Such calculations are planning exercises: they explore the number of participants per arm that might be needed under stated assumptions to detect an effect of a chosen size. They are not observed power, and they do not show that the trial had adequate or inadequate power. Since no primary outcome data were collected according to the outcome description, the registry record does not report an observed primary treatment effect to interpret. The underlying numerical planning results are not included in the record details summarized for this analysis.

Why can over-dispersion matter?

In general, over-dispersion occurs when the variability in data is greater than a model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. If variability is modeled appropriately, uncertainty estimates better reflect the observed spread. This concept is not a reported feature of the trial’s analysis: no analysis model, outcome distribution, variance estimate, or evidence of over-dispersion is reported in the registry record. It would be inappropriate to claim that over-dispersion was tested or corrected.

What does the registry report about outcomes?

The registry lists 3 outcome measures and describes secondary measures including change in EORTC-CIPN20 score and sensorimotor function. It reports 0 analyses. That combination does not provide estimates of secondary outcomes, their uncertainty, or any tests. The record does not report whether other planned measures were collected, whether analyses were attempted outside the registry, or how any such analyses were conducted. No claims about secondary effects can be made from outcome names alone.

The registry’s description that results are combined and cannot be presented per arm is important for interpretation. A combined total cannot recover a treatment contrast when the randomized groups are not available as separate outcome groups. Randomization is valuable because it supports causal comparisons when implemented and followed by an appropriate analysis, but the design label alone does not establish that such a comparison occurred. In this record, the stated absence of randomization and participant outcome data prevents estimation of the planned arm difference.

10. Multiplicity, Missing Data and Analysis Populations

The trial listed several objectives beyond the primary BPI-SF question. These included other BPI-SF scales, EORTC-CIPN20, EORTC QLQ-C30, PROMIS-29, dose delivery, early treatment discontinuation, quantitative neurosensory testing, and an exploratory treatment interaction with chemotherapy type. The registry also lists change in EORTC-CIPN20 score and change in sensorimotor function as secondary outcomes. Considering many outcomes or subgroup questions can raise multiplicity concerns: when multiple statistical tests are performed, the chance of at least one apparently notable result can increase. In general, a prespecified hierarchy or adjustment can help interpret multiple tests, but the registry record does not report a multiplicity strategy or a statistical analysis plan.

No analyses are reported, and the primary outcome record states that no participant data were collected. Therefore, there are no reported tests for which to assess multiplicity adjustments, and no secondary estimates to interpret. Whether any outcomes were designated for formal testing, whether exploratory analyses were planned in detail, or whether an adjustment was intended is not reported in the registry record.

Missing-data methods are also not reported. The absence of collected participant data described for the primary outcome is different from an analysis in which some participants have missing follow-up measurements: the record does not give a dataset from which patterns of missingness or methods for handling it could be assessed. It does not report outcome completion, reasons for missing measurements, imputation, or sensitivity analyses.

The registry describes a randomized design but says participants were not randomized. It does not report an analysis population such as all randomized participants, all treated participants, or participants with complete measurements. The enrollment entry of 12 does not establish an analysis denominator. As a result, neither the population contributing to a treatment estimate nor the handling of participants after allocation can be evaluated. These omissions limit reproducibility and prevent assessment of whether the planned analysis matched the intended trial design.

11. 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.

The adverse-event listing gives an All Participants group. It reports 11 at risk for serious events, 0 affected by serious events, 11 at risk for other events, 0 affected by other events, and 0 deaths. These are the registry’s listed counts; they are not arm-specific and do not compare topical menthol with placebo lotion.

The count at risk is the denominator associated with the listing, while the affected count records the number listed as having an event. A zero affected count means no affected participants are recorded in that category in this listing. It does not establish that a treatment has no safety risks, particularly when the primary outcome record says the trial was terminated for poor enrollment and no participant data were collected. The safety counts should not be converted into a treatment comparison or used to infer which intervention participants received.

The primary outcome record says participants were not randomized, and the registry reports enrollment of 12 while the adverse-event listing gives 11 at risk in each category. The record does not explain the relation between these entries, or provide participant-level details. It is therefore safest to report the safety counts as recorded and note that the registry record does not provide a randomized, arm-by-arm safety analysis.

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

The registry record establishes that a Phase II trial was intended to compare topical menthol with placebo lotion for chemotherapy-induced peripheral neuropathy, using change in BPI-SF score from baseline to 6 weeks as the primary endpoint. It also establishes that the study was terminated because of poor enrollment. The primary outcome description says no participant data were collected and that participants were not randomized. These registry entries make the trial’s intended question clear, but they do not yield an answer about the relative outcome of the two interventions.

The record does not show that menthol improved pain, worsened pain, or produced outcomes similar to placebo. It also cannot establish that the interventions were equivalent, because equivalence requires a suitable design, prespecified criteria, and analyzable outcome data. No treatment effect, interval estimate, or primary statistical test is reported. The absence of an estimate should not be interpreted as a zero effect or as evidence in favor of either group.

The adverse-event listing reports zero affected participants in its serious-event and other-event categories, with 11 at risk in each category and zero deaths. Because the listing is combined, it does not compare safety by treatment. The record does not establish what participants received or clarify how these counts relate to the statement that no participant data were collected.

In general, a trial can answer a comparative question only when it yields usable outcome data from groups that can be contrasted under an appropriate analysis. That general principle helps explain why the planned randomized, masked design is not itself a treatment result. In this instance, the registry record describes the intended design but also states that randomization and outcome data did not occur. Thus, conclusions about efficacy, comparative safety, precision, or clinical importance are not supported by the posted results. The appropriate reading is that the registry documents an incomplete trial and an unanswered treatment question.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a planned design and an estimable result. Randomization, masking, a comparator, and a defined endpoint can set up a useful treatment comparison, but those features do not substitute for observed outcomes. The registry describes a randomized, placebo-controlled, triple-masked design, yet the primary outcome record says participants were not randomized and no participant data were collected. The contrast the trial intended to estimate therefore is not available.

The record also shows why outcome definitions and analysis populations need to be read together. BPI-SF change from baseline to 6 weeks is a defined outcome, and the registry explains the score’s direction and purpose. But a well-specified measurement cannot answer a treatment question without scores from participants in the relevant groups. Similarly, the enrollment entry of 12 does not establish that 12 participants contributed measurements or that any treatment comparison could be made.

There is also a practical interpretive lesson about safety summaries. A combined event listing can report counts, but without arm-specific data it cannot support a comparison between interventions. Counts should be described as recorded, alongside the limitations of their source and context, rather than treated as evidence about relative risk.

Finally, planning calculations and observed trial results answer different questions. A sample-size illustration based on an assumed or observed effect is not an outcome analysis and is not observed power. When a trial stops before collecting outcome data, statistical planning cannot recover the missing treatment effect. Clear reporting of termination and unavailable outcomes is therefore essential for readers to distinguish an unanswered question from a negative finding.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation is that the registry says the study was terminated because of poor enrollment and no participant data were collected. Participants were not randomized, according to the primary outcome record. Although the study is described as randomized and triple masked, the posted outcome information does not document implementation of those planned features. The intended comparison cannot be reconstructed from a combined total.

The record lists enrollment of 12, but does not report how that number relates to the safety listing of 11 at risk. It does not provide participant flow, numbers treated in each group, follow-up completion, or reasons for any difference in counts. The primary endpoint has no reported score summaries, change estimates, treatment contrast, uncertainty interval, or test result. Secondary outcomes are listed, but no analyses are reported.

The record also does not report the statistical analysis plan, sample-size justification for the trial itself, interim analyses, missing-data procedures, analysis populations, multiplicity strategy, or model details. These omissions mean it is not possible to evaluate whether a completed analysis followed the protocol or how results would have been handled. The record does not provide enough detail to assess the reasons for poor enrollment beyond that statement.

The safety listing is combined rather than arm-specific and reports no affected participants in the listed categories. That information cannot support a comparison between treatments, and its relationship to the primary outcome statement is not explained. These limitations concern the available registry record; they do not establish what might be present in other records or documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Topical Menthol for the Treatment of Chemotherapy Induced Peripheral Neuropathy — NCT01855607.
• Registry record last updated 2024-07-11; status last verified 2022-10.
• Results first posted 2024-07-11.
• 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.

18. Record Summary

The registry describes a Phase II randomized, placebo-controlled, triple-masked trial of topical menthol versus placebo lotion for chemotherapy-induced peripheral neuropathy. The primary endpoint was change in BPI-SF score from baseline to 6 weeks, with a stated objective focused on worst pain score. The planned application period was six weeks, with twice daily topical treatment.

The record lists enrollment of 12, a start date of 2013-08, primary completion in 2016-11, and terminated status. The primary outcome description says the trial was terminated for poor enrollment, no participant data were collected, and participants were not randomized. No analyses are reported. The record therefore provides no treatment-effect estimate or arm-by-arm comparison.

The adverse-event listing gives 11 at risk for serious events and 11 at risk for other events, with 0 affected in both categories and 0 deaths. The registry record does not explain how these counts relate to its primary outcome statement or provide a comparison by intervention.