Treatment of Breast Cancer-related Lymphedema With a Negative Pressure Device: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Breast Cancer-related Lymphedema With a Negative Pressure Device (NCT03252145), a randomized na study. The primary outcome is Recruitment Rates.

2. Clinical Question

The central statistical question is whether the study could recruit participants to a randomized comparison of these two approaches and provide descriptive information about the resulting groups and outcomes. The registry reports 28 enrolled participants. The primary result is reported as a recruitment rate for each group, but the registry does not provide a two-arm comparison estimate for that endpoint. The stated reason is that the values were missing or not estimable for a two-arm comparison of a count-type endpoint.

Secondary measurements included limb volume, L-DEX® scores, skin induration, and shoulder range of motion. Posted secondary results include selected measurements at baseline and at 4 weeks. These outcomes can help describe what was measured in the feasibility study, but they are not a substitute for the primary recruitment endpoint, and the registry does not report a confirmatory analysis plan tying them to a treatment-effect conclusion.

3. Trial Design

The registry describes a randomized, parallel-group study with single masking and an enrollment of 28. The study status is completed. Its brief description calls it a 4 to 6 week randomized, controlled, assessor-blinded trial in breast cancer patients with chronic upper-extremity lymphedema. The masking field itself says single; the record does not specify further which people were masked beyond the assessor-blinded description.

Participants were assigned to negative-pressure massage using PhysioTouch or to manual lymph drainage. Both arm descriptions specify treatment to the lymphedematous upper limb 3 times a week for 4 weeks. The record lists 13 participants in the manual lymph drainage group and 15 in the negative-pressure group. The study is listed as phase NA.

The record gives a start date of 2017-10-31 and a primary completion date of 2020-01-31. It identifies recruitment rates as the primary endpoint, with a timeframe of 4 weeks. Secondary measures include limb volume, L-DEX® ratio scores and scores, skin induration, and shoulder range of motion. Some of these measures appear at more than one time point or as separate measures, and the record includes many outcome measures and analyses.

This is a small feasibility study, and its primary endpoint concerns recruitment rather than a clinical change measure. The record does not report a formal sample-size justification, a prespecified treatment-effect threshold, or enough detail to reconstruct the full analysis protocol. The sample-size planning illustrations associated with the posted secondary comparisons are based on observed effects; they are not evidence of the study’s original design target or of observed power.

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: Of the 130 who expressed interest in the study, only 28 met all inclusion criteria.

Overall Study

Reasons for not completing this period:

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 Recruitment Rates, measured over At 4 weeks.

The primary endpoint is recruitment rate at 4 weeks. The registry defines it as the number of women who were screened and then enrolled divided by the total number of women screened overall. Recruitment is a feasibility outcome: it describes how well the study enrolled people from those screened, rather than measuring the effect of treatment on limb volume, symptoms, or function.

The registry reports a rate value of 32.5 for the manual lymph drainage group and 37.5 for the negative-pressure group. The corresponding group counts are 13 and 15. No spread or interval estimate is posted for this endpoint. The record also does not provide the screened denominators needed to independently interpret the recruitment rates as a proportion of all screened women.

Although the primary endpoint is reported by group, a two-arm comparison is not available. The registry states that values were missing or not estimable for a two-arm comparison of this count-type endpoint. Therefore, the posted numbers are descriptive recruitment results; they do not establish a statistically estimated difference between groups. The record does not report an inferential test, confidence interval, or other comparative estimate for recruitment.

In general, a feasibility trial may use recruitment to assess whether a larger study can enroll participants and carry out its procedures. That general purpose does not establish whether recruitment would be adequate for a future study: the record does not report a target recruitment rate or a prespecified feasibility threshold against which these values could be judged.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies recruitment rates as the primary endpoint and reports selected continuous secondary outcomes as group means with standard deviations. Different statistical questions apply to these outcome types. Recruitment is a count-type feasibility measure, while limb volume and L-DEX® scores are continuous measurements. The registry does not post a comparative analysis for the primary recruitment endpoint, so the interpretation of the primary result is limited to the reported group values.

What does a mean difference describe?

For the continuous outcomes, a mean difference expresses the difference between the group means in the units of the outcome. A positive estimate in the posted comparisons indicates a higher mean in the negative-pressure group than in the manual lymph drainage group, given the comparison direction used. It is a difference between group summaries, not an adjusted estimate of change over time. In particular, the baseline comparisons describe group values at baseline; they do not estimate a treatment effect.

The posted comparisons include intervals around the mean differences. In general, a confidence interval describes a range of estimates compatible with the observed data under the analysis assumptions. An interval that includes no difference indicates that the data do not sharply separate a difference from no difference. A wide interval indicates limited precision. The confidence level for the posted intervals is not reported in the registry record, so it should not be assigned a level that the record does not state.

How should the p-values be read?

A p-value describes how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It does not give the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry reports two-sided t-tests for the selected continuous comparisons. A two-sided test evaluates departures in either direction. The record does not report further details of the test implementation or adjustment for covariates.

The posted unadjusted recalculations use the group means, standard deviations, and sample sizes to form comparisons. Those recalculated values differ from the registry-reported p-values for the displayed outcomes. The record’s reported test results and the unadjusted recalculations are therefore best treated as distinct analyses. The recalculations do not reproduce an unreported protocol analysis and do not replace the study’s recorded test results.

Why does over-dispersion matter in general?

General statistical principle: when count data vary more than a simple count model assumes, uncertainty can be understated if that extra variability is ignored. This is called over-dispersion. A suitable analysis should account for the distribution and variability of the counts. The registry does not report a comparative model for recruitment, so there is no basis to say whether or how over-dispersion was assessed for the primary endpoint.

What do the planning illustrations mean?

The planning illustrations are derived from the observed secondary-outcome effects, not from the study’s documented design justification. They use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with scenarios based on detecting the full observed effect or a stated fraction of it. The displayed estimates are participants per arm for 80% or 90% power under those assumptions. They are hypothetical planning quantities, not observed power, and they should not be interpreted as the study’s enrollment target or as evidence that the study was adequately powered for its endpoints. The record does not report the original sample-size assumptions or justification.

General statistical principle: power is a property of a planned design under specified assumptions, not a retrospective probability that a result is correct. A planning calculation based on an observed effect is particularly sensitive to the observed estimate, which may be unstable in a small feasibility sample. Such illustrations can help frame future-study planning, but they cannot repair missing design documentation or turn exploratory results into confirmatory evidence.

How should baseline and follow-up measurements be distinguished?

Baseline values describe the groups before the four-week treatment endpoint. A baseline comparison can reveal imbalance in the observed group summaries, but it is not an estimate of improvement or worsening under treatment. A follow-up comparison at 4 weeks is also a difference between group means at that time unless an analysis explicitly models change or adjusts for baseline. The registry does not report such an adjusted analysis for the selected outcomes. No change score should be inferred by subtracting the posted baseline and follow-up means.

In general, uncertainty reflects both the variability in measurements and the number of participants contributing data. Standard deviations describe variation among participants within groups; they are not standard errors or confidence intervals. The registry provides group sizes and standard deviations for the selected continuous outcomes, but does not report outcome-specific missingness or the number analyzed for every result. That limits assessment of how much data contributed to each comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures and 43 analyses, and it reports 28 secondary outcomes posted. This is a broad set of measures and analyses. The record does not report whether the investigators prespecified a hierarchy among outcomes, selected a limited family of comparisons for inference, or adjusted for multiple testing. Without that information, nominal p-values from secondary analyses should be interpreted cautiously: examining many outcomes can increase the chance of at least one apparently unusual result even when no corresponding effect exists.

Missing-data methods are not reported in the registry record. The record does not state how missing measurements were handled, whether participants with incomplete follow-up were included in particular analyses, or whether any imputation or sensitivity analysis was used. It also does not report the number analyzed for every endpoint and time point. As a result, the completeness of the secondary data and the assumptions behind each analysis cannot be assessed from the posted information.

The analysis populations are not reported in the registry record. It is not stated whether the analyses followed assignment regardless of treatment received, included only participants who completed treatment, or used another population definition. The record also does not describe exclusions, protocol deviations, or how adherence was handled. These details matter because exclusions after randomization can affect the balance created by random assignment.

The primary recruitment endpoint has an additional limitation: the registry says a two-arm comparison was not available because values were missing or not estimable for this count-type endpoint. The screened denominators and a comparative estimate are not reported. Therefore, the primary endpoint cannot be evaluated inferentially from the record, and the posted group values should not be mistaken for a tested treatment contrast.

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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among the 13 participants at risk in the manual lymph drainage group and among the 15 participants at risk in the negative-pressure group. No deaths are reported in either group. The serious adverse event terms list is empty.

Other adverse events are recorded for 1 participant in the manual lymph drainage group and 4 participants in the negative-pressure group, among 13 and 15 participants at risk, respectively. These are registry counts of participants affected; the record does not provide event descriptions in this summary or state how events were attributed to treatment. The figures should be read as recorded safety counts, not as evidence that an intervention caused or prevented an event.

Zero recorded serious events in these small groups does not establish that serious events cannot occur. Safety counts in a feasibility study are descriptive, and the record does not report a comparative safety analysis or the duration and completeness of safety follow-up beyond the stated study treatment period. The absence of listed serious-event terms should not be expanded into a broader claim about safety.

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

The record supports a limited description of a completed randomized feasibility study with 28 enrolled participants, comparing negative-pressure massage with manual lymph drainage. The primary endpoint was recruitment rate, and the reported group values were 32.5 and 37.5. A comparative estimate for recruitment is not available in the registry record, so the figures do not establish a difference between the groups.

Selected secondary measurements provide descriptive information about limb volume and L-DEX® scores at baseline and at 4 weeks. The posted estimates are uncertain, and the reported tests and summary-statistic recalculations are not identical. These results do not establish that one approach is superior, equivalent, or ineffective. The registry does not report a prespecified margin for equivalence or a complete confirmatory analysis plan, and failure to show a clear difference is not evidence that the approaches are the same.

General statistical principle: a nonsignificant result can arise when the true difference is small, when measurements are variable, or when the study has limited precision. It cannot by itself distinguish among those possibilities. Likewise, an estimated difference is not necessarily clinically important; clinical importance requires context and criteria that are not reported for these comparisons.

The planning illustrations based on observed secondary effects may help frame possible future-study sizes under their stated assumptions. They are not observed power, and they do not establish what sample size the investigators originally intended. The record does not report the original sample-size rationale, analysis populations, missing-data methods, or multiplicity strategy.

Accordingly, the defensible interpretation is that the registry records a feasibility study and a set of descriptive secondary results with substantial limitations for confirmatory inference. The data do not support medical advice or a treatment recommendation.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial statistics: a feasibility endpoint and a clinical outcome answer different questions. Recruitment rate concerns whether eligible people can be enrolled from those screened. It does not directly measure whether a treatment changes lymphedema. Here, recruitment is the primary endpoint, but the record does not provide the screened denominators or a two-arm comparative estimate. That makes clear reporting of the endpoint definition and its denominator especially important.

The study also shows why small feasibility studies need cautious interpretation of secondary outcomes. Group means and standard deviations can describe observed data, but a small sample can leave estimates imprecise. A p-value alone does not express precision or clinical importance. Intervals around estimates are informative because they show the range of differences compatible with the data under the analysis assumptions; in these results, uncertainty is substantial.

Another statistical lesson is that the analysis record matters. The registry includes many outcomes and analyses, but does not report the multiplicity plan, missing-data handling, or analysis populations. Without those details, it is difficult to distinguish planned confirmatory comparisons from exploratory ones or to determine how incomplete observations were handled. The registry also reports test p-values that differ from unadjusted summary-based recalculations, so careful attribution of each result to its analysis is necessary.

Finally, sample-size calculations based on observed effects are planning illustrations, not retrospective proof that a study had adequate power. Their assumptions should be explicit, and the resulting quantities should not be confused with the original design justification. These points are broadly useful when reading feasibility trials: focus first on the stated feasibility question, then treat clinical outcome comparisons in light of their precision and reporting limitations.

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 study enrolled 28 participants, with group sizes of 13 for manual lymph drainage and 15 for negative-pressure massage. The small sample limits the precision of group comparisons, as reflected in the uncertainty around the posted continuous-outcome estimates. The record does not provide a formal original sample-size rationale, so it is not possible to judge the intended precision for the primary or secondary endpoints against a documented target.

The primary recruitment result is incomplete for comparative interpretation. Although group rates are reported, screened denominators and an inferential comparison are not available. The registry explicitly notes that values were missing or not estimable for a two-arm comparison of the count-type endpoint. There is no reported target or threshold for deciding whether recruitment was feasible.

The study description says 4 to 6 weeks, while the arm descriptions specify treatment 3 times a week for 4 weeks and selected follow-up outcomes are reported at 4 weeks. The record does not provide further detail on timing beyond these descriptions. It also does not report the full masking procedures beyond the single-masking field and the assessor-blinded summary description.

Secondary outcomes are numerous, and the record does not report a multiplicity plan, missing-data methods, or analysis populations. Some outcomes appear more than once in the measure list, and only selected measures have detailed posted results in the summary. The reported analyses and the unadjusted recalculations are not identical for the displayed comparisons, reinforcing the need to keep their sources distinct. Finally, the safety counts are descriptive, and the registry does not provide detailed event terms or a comparative safety analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Breast Cancer-related Lymphedema With a Negative Pressure Device — NCT03252145.
• Registry record last updated 2021-01-15; status last verified 2020-12.
• Results first posted 2021-01-08.
• 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.

18. Record Summary

NCT03252145 is a completed randomized, parallel-group feasibility study of negative-pressure massage and manual lymph drainage for breast cancer-related upper-extremity lymphedema. The registry lists single masking, phase NA, and an enrollment of 28. Treatment in both arms was described as occurring 3 times a week for 4 weeks.

The primary endpoint was recruitment rate at 4 weeks. The registry reports group values but does not provide a comparative estimate because the count-type endpoint was not estimable for a two-arm comparison. Posted secondary results include limb volume and L-DEX® measurements. Serious adverse events and deaths are recorded as zero in both groups; other adverse events are recorded in each group.

The registry does not report the original sample-size justification, multiplicity strategy, missing-data methods, or analysis populations. Secondary comparisons and planning illustrations should therefore be interpreted as descriptive or exploratory rather than as definitive evidence about treatment effects.