Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer (NCT03139435), a na na study. The primary outcome is Tibial Nerve Cross-sectional Area.

2. Clinical Question

3. Trial Design

NCT03139435 is a completed pilot study sponsored by Wake Forest University Health Sciences. The registry describes a single-group model, with no allocation and no masking. Its enrollment is 20. The study is not a randomized comparison, so its participant group should not be interpreted as one arm of a randomized trial with a like-for-like control arm.

The intervention description says participants undergo peripheral nerve ultrasound and skin biopsy. Questionnaire administration is also listed. Ultrasound tomography is identified as the diagnostic test. The registry names nine outcome measures, including tibial nerve cross-sectional area, other nerve-response measures, skin nerve fiber density, a self-reported neuropathy score, and sural nerve cross-sectional area.

The primary outcome is tibial nerve cross-sectional area, measured by ultrasound up to 30 days. The planned comparisons use historical data from healthy patients and from patients with diabetic or oxaliplatin neuropathy. The record names a two-sample t-test for the healthy historical comparison, one-sample t-tests for the other historical comparisons, and a general linear model to evaluate factors that may be associated with nerve area.

The registry records a start date of 2017-05-11, a primary completion date of 2018-12-12, and a status of completed. Completion status is a record of study progress, not evidence that an outcome was measured in a particular way or that the planned analysis produced a particular result. Analysis results 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: Historical control information is a reference group only and were not active participants in this trial.

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 Tibial Nerve Cross-sectional Area, measured over Up to 30 days.

Tibial nerve cross-sectional area is the primary endpoint. It is an ultrasound measurement of the area of the tibial nerve, reported in mm^2. The registry specifies that it is measured up to 30 days. A continuous endpoint such as area retains information about the measured quantity rather than reducing it to a simple yes-or-no classification. In general, continuous measures can be compared between groups or against historical reference data using methods that assess differences in their means.

The endpoint is used to examine whether ultrasound-measured nerve area differs between the study sample and historical data from healthy patients, diabetic neuropathy patients, and oxaliplatin neuropathy patients. Those comparisons address the measurement’s potential relevance to detecting taxane-induced neuropathy; they do not, by themselves, establish diagnostic accuracy. Measures such as sensitivity, specificity, or a prespecified diagnostic threshold are not reported in the registry record.

The registry specifies a mean and standard deviation as the outcome summary, but does not report the observed mean, standard deviation, estimated differences, confidence intervals, or test results. The planned timeframe and statistical methods therefore describe how the endpoint was to be assessed, not what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods described in the registry record are plans for comparing a continuous measurement. They do not supply a result. The endpoint is tibial nerve cross-sectional area measured by ultrasound, summarized as a mean and standard deviation. The planned timeframe is up to 30 days. The record names comparisons with historical healthy patients, diabetic neuropathy patients, and oxaliplatin neuropathy patients.

What does a t-test assess?

In general, a t-test evaluates whether a difference in means is compatible with the variability observed in the data, under the assumptions of the test. A two-sample t-test compares the means of two groups. In this study plan, that method is named for the comparison between the study sample and historical healthy-patient data. The test does not adjust automatically for differences in other characteristics, and a test result alone does not communicate the size or practical importance of a difference.

A one-sample t-test compares the mean in one sample with a reference value. The registry names one-sample t-tests for comparisons with historical diabetic neuropathy and oxaliplatin neuropathy data. The record does not give the historical values or explain how the reference values were derived. It also does not report the test statistics, p-values, confidence intervals, or estimated differences. The stated method therefore cannot be used to reconstruct a finding.

Why does the historical comparison matter?

In general, a concurrent control group is measured in the same study context as the intervention group. Historical data come from observations collected earlier or in another setting. Differences in participant characteristics, measurement procedures, or data handling can influence a historical comparison. This is a potential source of bias, not proof that a particular comparison is biased. The registry record does not describe procedures for aligning the study sample with historical patients or accounting for differences between data sources.

The study is single-group, with allocation listed as NA and masking listed as none. It is therefore not a randomized, masked comparison of ultrasound against a concurrent control condition. This design can describe measurements in the enrolled group and compare them with historical reference data, but the design alone does not establish that an observed difference is caused by taxane exposure or that ultrasound distinguishes individual patients with neuropathy from those without it.

What would the general linear model add?

The registry says a general linear model would be used to evaluate factors, with age given as an example, that may be associated with nerve cross-sectional area. In general, a model can estimate the association between an outcome and one or more explanatory variables. Adjustment may help describe how measured characteristics relate to the outcome, but it does not guarantee that all relevant differences are controlled. Interpretation depends on the model specification, available observations, and assumptions. The detailed model, included factors, estimates, and diagnostics are not reported in the registry record.

For continuous outcomes, variation around the mean matters. The standard deviation describes the spread of individual measurements in the sample; it is not the same as the uncertainty around the estimated mean. A confidence interval, when reported, expresses uncertainty in an estimate under the analysis assumptions. No primary-endpoint standard deviation or confidence interval is reported, so neither the variability of the measurements nor the precision of a mean comparison can be evaluated from the registry record.

What does over-dispersion mean in general?

Over-dispersion is a concern mainly for outcomes analyzed with count-based models when the observed variability exceeds what the model assumes. It can make standard errors too small if not addressed. The primary outcome in this study is a continuous area measurement, and the registry names t-tests and a general linear model rather than a count model. No count-based primary analysis or over-dispersion assessment is reported. This general concept should not be mistaken for a reported feature of this trial’s data.

The registry lists nine outcome measures and 0 analyses. That information does not show which measures were collected or whether the named methods were ultimately applied. The analysis results and any departures from the planned methods are not reported in the registry record.

How should the sample-size illustrations be read?

The registry describes sample-size illustrations based on a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. In general, such calculations estimate the sample size associated with stated assumptions for a future planning scenario. The registry explicitly distinguishes these illustrations from the trial’s own design. They are not observed power, do not describe the single-group study’s actual allocation, and do not establish whether a result was detected. No calculated sample-size values are reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Case", "Control")
n   <- c(20, 60)
m   <- c(13, 14)
sp  <- c(3.6, 4.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Case  20  13.000  3.600  11.315  14.685
CARM  Control  60  14.000  4.300  12.889  15.111

11. Multiplicity, Missing Data and Analysis Populations

The registry record names nine outcome measures, while the number of analyses recorded is 0. It does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment to account for testing multiple outcomes. In general, testing multiple outcomes can increase the chance of at least one apparently notable result arising by chance. Whether and how that issue was addressed in this study is not reported in the registry record.

The primary endpoint is identified as tibial nerve cross-sectional area. The record also lists measures of nerve responses, nerve fiber density, self-reported neuropathy, and sural nerve area. Naming a primary outcome helps distinguish it from other measures, but does not show how results for the other outcomes were interpreted or whether analyses were prespecified in detail.

Handling of missing measurements, withdrawals, or incomplete questionnaires is not reported in the registry record. The analysis population is also not described. In general, missing data can affect estimates when the availability of measurements is related to participant characteristics or outcomes. Without counts of missing observations and a stated handling method, readers cannot assess whether the reported analysis—if any—used all enrolled participants or a subset.

The registry does not report an interim-analysis plan, imputation methods, or sensitivity analyses. These omissions should be read as information not reported in the registry record, rather than evidence that a particular procedure was or was not performed outside the record.

12. 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 adverse-event record identifies the group as Case. It reports serious adverse events for 0 of 20 participants at risk and other adverse events for 3 of 20 participants at risk. No deaths are reported. No serious adverse-event terms are listed, and the record does not name the other adverse events in the available summary.

These figures describe the adverse-event entries recorded for this group; they do not establish that every event was caused by ultrasound, biopsy, questionnaire administration, or another aspect of the study. The registry summary does not provide event descriptions, timing, severity details for the other events, or a causal assessment. The absence of listed serious-event terms should not be interpreted as a detailed account of event monitoring.

In general, safety counts are most informative when the event definitions, observation period, severity, and relationship to study procedures are clear. Those details are not reported in the registry record. The counts should therefore be read narrowly as the recorded serious and other adverse-event figures, not as a complete characterization of safety.

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

The registry record establishes that NCT03139435 was a completed pilot study with a single-group design and an ultrasound-based primary endpoint. Its planned statistical approach compared tibial nerve cross-sectional area with historical data and proposed a model to evaluate factors associated with that measure. These design details describe the research question and analysis plan; they are not evidence of an observed result.

No primary endpoint estimate, group variability, comparison result, confidence interval, or p-value is reported in the registry record. It is therefore not possible from this record to determine whether the study sample’s measured nerve area differed from any historical group, how large any difference was, or how precisely it was estimated. The record also does not report a diagnostic threshold or measures of diagnostic accuracy.

Even if a difference from historical data were reported, a difference in group means would not by itself show how well ultrasound classifies individual patients. In general, diagnostic performance requires information about how a test result relates to an appropriate reference assessment across individuals. Those details are not reported in the registry record. The historical-comparison design also does not provide a randomized, concurrent control group for attributing differences to a particular cause.

The enrollment of 20 and the pilot designation indicate the scale and stated purpose of the study, but do not determine whether a measurement is reliable or clinically meaningful. The sample-size illustrations are planning scenarios, not observed power and not evidence of a detected effect. The adverse-event counts are separate from the efficacy or diagnostic question and cannot fill the gap left by missing endpoint results.

Accordingly, the record supports a description of what the study planned to measure and compare, but not a conclusion about the success, failure, or accuracy of ultrasound for detecting taxane-induced neuropathy.

14. Why This Trial Matters Statistically

This study raises a statistical question that is common in diagnostic research: how should a new measurement be interpreted when its comparator information comes from historical data? The planned endpoint is a continuous ultrasound measurement, and the record names mean-based comparisons. Those methods can assess differences in average measurements, but their interpretation depends on how comparable the study observations are to the historical reference data.

The design makes the distinction between measurement and diagnosis especially important. A group-level difference in mean nerve area, if one were reported, would not by itself establish how accurately the measurement identifies neuropathy in an individual. Diagnostic evaluation generally requires participant-level comparisons against a clearly defined reference and reporting of performance measures. Such results are not reported in the registry record.

The study also illustrates why a stated analysis plan is not a substitute for an analysis result. The record names a primary endpoint and several statistical methods, but does not report estimates, uncertainty intervals, or test results. Without those, readers cannot assess the magnitude or precision of the measurement differences. A completed status does not resolve that uncertainty.

Finally, the registry lists multiple outcomes and planning illustrations, while its design is single-group. Keeping those elements distinct matters: the planning assumptions do not describe the observed design, and sample-size illustrations are not observed power. The record is therefore useful for understanding the intended measurement strategy, while leaving the central statistical evidence about the primary endpoint unavailable.

15. 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 primary limitation for interpreting the study statistically is that outcome estimates and analysis results are not reported in the registry record. The record identifies tibial nerve cross-sectional area and planned tests but provides no observed mean, standard deviation, comparison estimate, confidence interval, or p-value. The magnitude and precision of the primary finding therefore cannot be assessed.

The study uses historical comparison data rather than concurrent randomized controls. In general, historical groups may differ from the study sample in characteristics or measurement context, and such differences can complicate interpretation. The registry does not describe the source selection, matching, or harmonization of the historical data. The absence of allocation and the listing of no masking also mean that this is not a randomized, masked comparison.

The enrollment is 20 and the study is described as a pilot. The registry does not report a trial-specific sample-size justification. Its sample-size assumptions describe planning illustrations using equal allocation between two arms, which does not match the recorded single-group model. Those illustrations should not be treated as observed power or as evidence that the study was adequately powered for its primary question.

The record lists nine outcome measures and 0 analyses, but does not report a multiplicity approach, an analysis population, or procedures for missing data. It does not provide a detailed model specification or diagnostic performance measures. These omissions limit assessment of how the planned comparisons were carried out and what conclusions the data could support.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer — NCT03139435.
• Registry record last updated 2024-04-08; status last verified 2024-04.
• Results first posted 2024-04-08.
• 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.

19. Record Summary

NCT03139435, titled “Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer,” is a completed pilot study sponsored by Wake Forest University Health Sciences. The registry records a single-group model, no allocation, no masking, and enrollment of 20. The start date is 2017-05-11, and the primary completion date is 2018-12-12.

Participants undergo peripheral nerve ultrasound and skin biopsy; questionnaire administration is also listed. The primary outcome is tibial nerve cross-sectional area, measured in mm^2 up to 30 days. Planned comparisons use historical healthy, diabetic neuropathy, and oxaliplatin neuropathy data. The registry names t-tests and a general linear model but does not report outcome estimates or analysis results.

The adverse-event summary records 0 serious adverse events and 3 other adverse events in the Case group. Event details are not reported in the registry record. The record lists nine outcome measures and 0 analyses.