A Non-invasive Intervention (BreEStim) for Management of Phantom Limb Pain (PLP) After Limb Amputation (Experiment 1): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Non-invasive Intervention (BreEStim) for Management of Phantom Limb Pain (PLP) After Limb Amputation (Experiment 1) (NCT04750525), a non-randomized na study. The primary outcome is Change in Pain Level as Measured by the Visual Analog Scale (VAS)..

2. Clinical Question

The question is about a short-term pain-score change in people with phantom limb pain, rather than a long-term outcome. The primary endpoint is defined as the baseline VAS score minus the score 10 minutes after intervention. Under that definition, a positive change means the score decreased. This describes how the endpoint is constructed; it does not establish how participants’ scores changed in the study.

The crossover designation and the sequence labels indicate that intervention order is relevant to the design. However, the record does not provide enough detail to establish how the sequence was assigned, whether the same participants contributed outcome data after both interventions, or how any order or carryover effects were handled. The reported comparison should therefore be read in light of the non-randomized allocation and the absent outcome analysis.

3. Trial Design

The registry identifies this as a completed, non-randomized crossover study of BreEStim and EStim for phantom limb pain after limb amputation. Enrollment is 15. The record lists two sequence labels: BreEStim 120, then EStim 120; and EStim 120, then BreEStim 120. It describes BreEStim as voluntary breathing-controlled transcutaneous electrical nerve stimulation and EStim as transcutaneous electrical nerve stimulation. The unit or operational meaning of 120 is not reported in the registry record.

Non-randomized allocation matters because treatment order or assignment may be related to participant characteristics or other factors. The registry itself notes that the arms are not a like-for-like control comparison. Although the study model is recorded as crossover, the record does not report the sequence-assignment procedure or explain whether participants experienced both conditions. It also does not describe a washout period, intervention timing beyond the primary outcome timeframe, or measures to address carryover. These details are not reported in the registry record and should not be assumed.

Masking is listed as single, but the record does not state who was masked or how masking was maintained. The phase is listed as NA. The sponsor is The University of Texas Health Science Center, Houston. The study status is completed, with a start date of 2021-04-02 and a primary completion date of 2023-03-10.

The primary measure is change in VAS pain score from baseline to 10 minutes after intervention. The listed secondary outcomes are change in sensation threshold on the amputated limb measured by electrical sensation threshold and change in pain threshold on the amputated limb measured by electrical pain threshold. The record lists 4 outcome measures but 0 analyses. It does not report participant flow, analysis populations, or results for these outcomes.

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.

First Intervention (15-30 Minutes)

Washout (About 3-14 Days)

Second Intervention (15-30 Minutes)

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: 0 participants were assigned to the EStim 120, then BreEStim 120 arm.

6. Primary Endpoint

The registry lists the primary outcome as Change in Pain Level as Measured by the Visual Analog Scale (VAS)., measured over Baseline, 10 minutes after intervention.

The primary endpoint is change in pain level measured by the Visual Analog Scale. The scale runs from 0 to 10, with 0 meaning no pain and 10 meaning worst pain; higher scores indicate higher pain. The registry defines change as the baseline score minus the score 10 minutes after intervention. With this direction of subtraction, a positive value represents a lower score after intervention.

A pain scale provides a way to quantify a participant’s reported pain at specified assessment times. Comparing the score after intervention with baseline can describe short-term change while retaining the scale’s direction and units. The endpoint is a score on a scale, and the registry specifies a mean and standard deviation as its summary format. Those summaries can describe the average change and the spread of participant-level changes if the data and analysis are reported.

The record does not include baseline or post-intervention scores, mean changes, standard deviations, confidence intervals, or a comparison between BreEStim and EStim. Therefore, the endpoint definition alone does not show the magnitude, direction, or precision of any observed difference. The timing also limits what this measure addresses: the specified post-intervention assessment is 10 minutes after intervention, not a later follow-up. Other measurement timepoints are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint measure?

The primary endpoint is a continuous measure: the VAS score difference defined as baseline score minus score 10 minutes after intervention. The registry specifies a mean and standard deviation for this outcome. A mean describes the average of the measured changes, while a standard deviation describes how dispersed individual changes are around that average. These summaries answer different questions: the mean concerns the average change, and the standard deviation concerns variability among observations.

The endpoint’s subtraction order determines its sign. A positive value means the later score is lower than baseline according to the registry’s definition. A negative value means the later score is higher. These are interpretations of the defined measure, not descriptions of the trial’s findings. The record supplies no mean change or standard deviation, so the summaries cannot be evaluated for this study.

What would a treatment comparison require?

A comparison of the interventions would need to specify which outcome observations are being contrasted and how they relate to the crossover design. In a crossover study, a participant may contribute observations under more than one intervention, so an analysis may need to account for the relationship between observations from the same participant. This is a general statistical consideration, not a statement about the analysis used in this study. The registry records the study model as crossover but does not report the statistical model, the treatment contrast, or whether the analysis used paired participant-level data.

Order may also matter in a crossover design. A participant’s outcome after an intervention could depend on the sequence or on effects that persist from an earlier intervention. General crossover analyses may consider period, sequence, or carryover effects when the design and data support doing so. The registry record does not describe whether such effects were assessed or how they were handled. It would be inappropriate to assume that a particular adjustment or test was performed.

Interpretation also depends on allocation. Here, allocation is recorded as non-randomized, and the record cautions that the arms are not a like-for-like control comparison. In general, non-random allocation can leave groups different for reasons related to who received each sequence or when. Statistical adjustment can sometimes address measured differences, but cannot automatically remove unmeasured differences. The registry record does not report adjustment variables or an adjusted analysis.

How should uncertainty be understood?

A confidence interval is a statistical summary of uncertainty around an estimated effect. Its width reflects the precision of that estimate under the analysis assumptions; a narrower interval generally indicates greater precision, while a wider interval indicates less. A confidence interval also helps readers assess which effect values remain compatible with the observed data and method. No confidence interval or effect estimate is reported in the registry record.

A p-value, if reported, would describe how compatible the observed data are with a specified null model, given the analysis assumptions. It would not measure the probability that an intervention is effective, nor would it describe the size or importance of an effect. No p-value is reported. The record also does not state the statistical test or model used for the primary endpoint.

The primary endpoint is continuous and is described using a mean and standard deviation. In general, a mean-based analysis may be sensitive to skewness or unusual observations, depending on the data and method. The registry record does not provide outcome distributions, diagnostic checks, or details about how the assumptions of any analysis were assessed. No specific assumption check can be attributed to this study.

What does the planning approach say?

The registry describes sample-size assumptions as a planning illustration rather than the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The record does not include the resulting planning estimates or identify a sample-size justification used to design the study.

A planning calculation asks how many participants might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. Such a calculation depends on the effect size and variability assumed, as well as design and analysis choices. Since the record does not report the observed effect or the resulting planning values, no numerical planning conclusion can be drawn. These calculations are not observed power, and they do not indicate whether the completed study detected an effect.

For a crossover design, planning assumptions would ordinarily need to reflect the within-participant structure and intended analysis. The record’s stated illustration instead specifies equal allocation between two arms and a normal approximation; it does not explain how that illustration relates to the crossover sequences. This relationship is not reported in the registry record. The illustration should therefore be read as a stated planning framework, not as evidence that a particular design calculation or analysis was used.

What can be concluded from the posted analysis information?

The registry lists 4 outcome measures and 0 analyses. In statistical terms, a listed outcome identifies something to be measured, but does not provide an estimate or test of that outcome. Without reported results, readers cannot assess the observed effect, its uncertainty, the number of participants included in the analysis, or how well the analysis followed the planned design. The record does not report a statistical analysis plan, model specification, missing-data method, or analysis population.

These absences are important because the endpoint definition and design label alone do not determine the appropriate analysis. A transparent report would connect the outcome definition to the analyzed observations, identify the treatment contrast, describe how the crossover structure and non-random allocation were handled, and provide effect estimates with uncertainty. Those details are not reported in the registry record. General statistical considerations can explain what such information would mean, but cannot substitute for the study’s own analysis.

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("BreEStim 120", "EStim 120")
n   <- c(15, 15)
m   <- c(1.38, 1.27)
sp  <- c(1.24, 1.13)
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  BreEStim 120  15  1.380  1.240  0.693  2.067
CARM  EStim 120  15  1.270  1.130  0.644  1.896

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary VAS pain-change outcome and two secondary outcomes: change in sensation threshold measured by electrical sensation threshold, and change in pain threshold measured by electrical pain threshold. It lists 4 outcome measures overall and 0 analyses. The record does not report how the listed outcomes were analyzed or whether additional comparisons were planned.

Multiplicity arises when several outcomes, timepoints, groups, or statistical tests are examined. As the number of tests grows, the chance of finding at least one apparently notable result by chance can increase. General approaches include identifying a primary outcome in advance, adjusting inference for a defined family of tests, or clearly treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among the outcomes, or an analysis plan. No correction or testing hierarchy should be assumed.

Missing-data handling is also not reported in the registry record. The enrollment is 15, but the record does not give the number with observed baseline and post-intervention VAS scores, the number included in any analysis, reasons for missing observations, or a method for handling missing data. Enrollment should not be treated as the analyzed sample size. The record does not report whether all enrolled participants were included in an analysis or how incomplete crossover observations were treated.

Analysis populations are not described. The record does not identify an intention-to-treat, per-protocol, or other population, and does not explain whether participants were analyzed according to sequence, intervention received, or available outcome data. These details matter for interpreting the target of an estimate and potential selection effects. In their absence, neither the population represented by any analysis nor the consequences of missingness can be assessed from the registry 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for both sequence groups. For BreEStim 120, it reports 15 participants at risk, 0 affected by serious adverse events, and 0 deaths. For EStim 120, it reports 15 participants at risk, 0 affected by serious adverse events, and 0 deaths. No serious adverse-event terms are listed among the leading terms.

The record also reports other adverse events for each group: 15 participants at risk and 15 affected in the BreEStim 120 group, and 15 at risk and 15 affected in the EStim 120 group. The record does not provide event terms or describe the nature, severity, timing, or relationship of these other events. A count of affected participants does not indicate the number of events per participant.

These are registry safety counts, not a complete clinical interpretation of risk. Enrollment is 15 and 15 participants are listed at risk in each group, but the record does not clarify participant overlap between the sequence groups or how the crossover design was reflected in these summaries. The counts should not be treated as evidence that the groups are independent. The absence of reported serious events in these entries does not establish that no adverse experiences occurred; the other-event counts are reported separately and are not described in detail.

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

The registry record establishes that a completed study was designed to compare BreEStim and EStim for phantom limb pain after amputation. It specifies a short-term primary pain measure and lists electrical sensation and pain thresholds as secondary outcomes. It also records an enrollment of 15, a non-randomized allocation, a crossover model, and two sequence labels.

What it does not establish is the result of the comparison. The record reports 0 analyses and does not include primary or secondary outcome estimates. There is no reported mean change in VAS score, treatment contrast, confidence interval, or p-value. Without these, the direction, magnitude, and precision of any observed outcome cannot be assessed. The endpoint definition tells readers how to interpret a value if one is reported, but does not show that the score changed.

The design labels also do not resolve all questions needed to interpret a comparison. Non-randomized allocation means the registry cautions against treating the arms as a like-for-like control comparison. The crossover designation and order labels make within-participant structure and treatment sequence relevant, but the record does not explain assignment, carryover handling, or the statistical model. These are limitations on what can be inferred from the registry entry, not evidence for or against a particular treatment effect.

The safety entries report 0 serious adverse events and 0 deaths in each listed group, alongside 15 participants affected by other adverse events in each group. The other events are not described, and the record does not clarify overlap across sequence groups. Those counts cannot characterize the kinds or severity of events.

Accordingly, the record supports a description of the trial’s question, design, and registered outcome definitions. It does not support a conclusion about comparative efficacy, equivalence, or safety. Missing results should not be interpreted as a finding of no effect.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registry combines a crossover model with non-randomized allocation. A crossover design can permit comparisons within participants, which may help account for stable differences between people. That potential advantage depends on the actual sequence assignment, repeated measurements, and analysis. The record does not report whether participants contributed data under both interventions or how the within-participant relationship was modeled.

Non-randomized allocation places a separate constraint on interpretation. The registry expressly states that the arms are not a like-for-like control comparison. If outcomes differed between sequence groups, differences might reflect allocation or other factors rather than intervention alone. The record does not report adjustments or methods intended to address such differences.

The endpoint definition is also consequential. It specifies baseline VAS minus the score 10 minutes after intervention, so positive values represent a decrease in the score. Stating the direction of subtraction helps avoid reversing the meaning of an estimate. Yet the registry does not report an estimate or analysis, leaving readers unable to apply that interpretation to observed results.

Finally, the record lists multiple outcome measures but no analyses. This distinction matters: registered outcomes identify intended measurements, whereas analyzed results are needed to evaluate effect size, uncertainty, and the treatment comparison. The absence of those results makes the record more useful for understanding the study’s design than for judging its statistical findings. It also makes clear why sequence details, analysis populations, missing-data handling, and multiplicity methods are important for a transparent interpretation.

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 main limitation for interpretation is the absence of posted outcome analyses. The registry lists 4 outcome measures but 0 analyses, and does not provide estimates or uncertainty for the primary VAS endpoint. The number of participants with usable outcome data is not reported in the registry record. Enrollment of 15 alone cannot establish the analyzed sample size or the precision of an estimate.

The allocation is non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. The crossover model and sequence labels do not supply the missing details about assignment, the observations contributed by each participant, or the analysis of treatment order. The record does not report whether potential carryover was considered or how it was handled.

Important protocol and analysis details are also absent. The registry does not identify who was masked, define the unit or meaning of 120 in the sequence labels, describe a washout period, or report the statistical model. It does not state the analysis population, missing-data method, multiplicity approach, or whether the listed secondary outcomes were analyzed. The rationale for the enrollment target is not reported in the registry record; the stated sample-size assumptions are described as an illustration and do not provide calculated estimates.

For safety, the record provides counts but no descriptions of the other adverse events, and does not clarify whether participants appear in both sequence-group summaries. These omissions prevent a detailed assessment of the safety data. Together, the limitations mean that the registry record supports a design-level account, not a quantitative assessment of treatment effects or their precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Non-invasive Intervention (BreEStim) for Management of Phantom Limb Pain (PLP) After Limb Amputation (Experiment 1) — NCT04750525.
• Registry record last updated 2025-03-12; status last verified 2025-02.
• Results first posted 2025-03-12.
• 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

NCT04750525 is a completed, non-randomized crossover study sponsored by The University of Texas Health Science Center, Houston. The registry lists enrollment of 15, phase NA, and single masking. Its stated purpose is to compare breathing-controlled electrical stimulation, BreEStim, with conventional electrical stimulation, EStim, for phantom limb pain after amputation.

The primary outcome is change in VAS pain score from baseline to 10 minutes after intervention, defined as baseline score minus the later score. Secondary outcomes concern sensation and pain thresholds measured by electrical thresholds. The registry lists 4 outcome measures and 0 analyses. It does not report outcome estimates or statistical tests. The safety entries report 0 serious adverse events and 0 deaths in each listed group, as well as 15 affected by other adverse events in each group; descriptions of those other events are not reported in the registry record.