Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL (NCT02609724), a randomized na study. The primary outcome is Lymphoedema Volume at the Level of the Arm/ Hand.

2. Clinical Question

The trial asked whether fluoroscopy-guided manual lymph drainage (MLD), when used as part of decongestive lymphatic therapy, differed from traditional MLD or placebo MLD for people with breast cancer-related lymphoedema (BCRL). The registry identifies the primary outcome as lymphoedema volume at the level of the arm and hand, expressed as an inter-limb ratio. Its primary assessment was after 3 weeks of intensive treatment. The record does not report the primary outcome values or an inferential comparison among the three groups, so the magnitude and precision of any observed difference cannot be described from the registry record.

3. Trial Design

This was a randomized, parallel-group trial with three arms: fluoroscopy-guided MLD, traditional MLD, and placebo MLD. The registry records triple masking; its brief summary describes the study as double-blinded. These are the registry's descriptions, and the record does not explain the masking procedures or clarify the difference in wording. The trial is identified as multicentric in its brief summary and as completed in its status field. Phase is listed as NA.

Enrollment was 194. Each arm description includes information, skin care, compression therapy, exercises, and the assigned MLD approach. Intensive treatment lasted 3 weeks and comprised 14 sessions of 60 minutes. This was followed by 6 months of maintenance treatment comprising 18 sessions of 60 minutes, then 6 months of follow-up. The primary endpoint was assessed after the intensive treatment period, rather than at the end of maintenance or follow-up.

The registry lists a start date of 2016-01 and primary completion of 2020-03. Universitaire Ziekenhuizen KU Leuven is listed as the sponsor. Although the record reports enrollment and describes three treatment groups, it does not report the randomization method, allocation concealment, group-specific enrollment at assignment, or reasons for discontinuation apart from the follow-up information stated for the primary assessment. Those details should not be inferred from the randomized, parallel-group labels.

The intervention comparison is embedded within a broader care program: the assigned MLD approach varied, while the arm descriptions share the other listed components and treatment schedule. The record does not provide enough detail to determine how consistently each component was delivered or whether participants received additional care outside the listed interventions.

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: At the post-intensive assessment, 5 patients dropped-out of which 4 patients (2%) were lost to follow-up.

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 Lymphoedema Volume at the Level of the Arm/ Hand, measured over Primary endpoint = After 3 weeks of intensive treatment.

The primary endpoint is lymphoedema volume at the level of the arm and hand, expressed as an inter-limb ratio. The registry defines the ratio using the combined volume of the arm and hand on the affected side divided by the corrected combined volume of the arm and hand on the healthy side. Arm volume is estimated from circumference measurements using the truncated cone formula; hand volume is measured by water displacement. The healthy-side arm volume is corrected for hand dominance because the registry notes an average size difference between dominant and non-dominant limbs.

This relative measure compares the affected limb with the opposite limb rather than relying only on an absolute volume. In general, a within-person comparison can account for some differences in body size between participants. However, it also depends on the healthy-side measurement and the stated correction. The registry does not report the actual ratio values, how they changed from baseline, or the comparison between treatment groups.

The designated primary assessment was after 3 weeks of intensive treatment. The record also describes the ratio at different time points, but does not provide a single reported result for the primary outcome. Therefore, the measure and its intended assessment are clear, while the observed endpoint value and its uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial's randomized, parallel-group design means participants were assigned to one of three treatment groups, with each group receiving its assigned MLD approach alongside the other listed components of decongestive lymphatic therapy. In general, random assignment is used to reduce systematic differences between groups at the start of a study. The registry does not report how the sequence was generated, how assignment was concealed, or whether the groups were balanced on baseline characteristics. Those aspects of the randomization process cannot be assessed from the record.

What does the primary measure represent?

The primary measure is a continuous quantity: the mean arm/hand inter-limb ratio. It is formed from the combined volume of the affected arm and hand relative to the corrected combined volume of the healthy arm and hand. The registry describes circumference-based arm volume estimates using the truncated cone formula and hand volume measurement by water displacement. It also specifies correction of the healthy-side arm volume for hand dominance. In general, a ratio places two measurements on a relative scale, but its interpretation depends on how both sides are measured and on the correction applied.

The primary assessment time is after 3 weeks of intensive treatment. Although the registry describes the ratio at different time points, it does not post a set of endpoint values or an analysis comparing the groups. A statistical description of a continuous endpoint would ordinarily include group summaries and an estimate of the between-group contrast, together with uncertainty. The record specifies a mean and 95% confidence interval as the outcome format, but does not report the numerical estimates or intervals.

How should a confidence interval be understood?

In general, a confidence interval describes the uncertainty associated with an estimate under the statistical method used. A narrower interval indicates greater precision in that estimate, while a wider interval indicates less precision. A 95% confidence interval is the level named for this outcome in the registry; the actual interval limits are not reported. Without an estimate and its interval, the direction, magnitude, and precision of a group difference cannot be evaluated.

Statistical significance and clinical importance are different ideas. In general, a significance test assesses compatibility between observed data and a specified null hypothesis under its assumptions; it does not by itself establish whether a difference matters to patients. This trial's registry record does not report the primary test, its p-value, a clinically meaningful threshold, or a statistical analysis plan. None should be inferred from the design description alone.

What does the treatment structure imply for interpretation?

All three arm descriptions include information, skin care, compression therapy, and exercises, with the MLD approach differing across groups. A comparison between groups would therefore concern the assigned MLD approaches within the listed treatment program, rather than comparing the entire program with no treatment. The record does not report how these shared components were standardized or measured, so their delivery cannot be assessed from the registry description.

In general, a placebo comparison can help distinguish the effect associated with the active treatment approach from effects associated with attention or the broader care setting, depending on what the placebo entails. The registry labels one group as placebo MLD but does not describe the placebo procedure in enough detail to characterize its similarity to the other MLD approaches. The exact interpretation of that contrast consequently depends on details not reported in the registry record.

What can planning calculations tell readers?

Planning sample-size calculations are illustrations of how many participants might be needed under stated assumptions; they are not observed power and do not describe the achieved precision of a completed trial. The registry's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. The registry record does not report the primary observed effect or the analysis results needed to interpret such calculations as evidence about the trial's findings. They should not be read as a substitute for the unreported endpoint estimates.

In general, a planning estimate depends on assumptions about the effect size, variability, allocation, and statistical method. Changing those assumptions changes the illustrative sample size. A planning calculation cannot establish that a study was adequately powered for every outcome, especially when the analysis method, variance assumptions, and outcome-specific targets are not reported. The registry does not provide the trial's own sample-size justification, so it is not possible to determine from this record how enrollment of 194 was selected.

Why do distributional assumptions matter?

Continuous outcome analyses often rely on assumptions about how measurements behave and how their variability is represented. In general, unusually skewed data or unequal variability between groups can affect the validity of simple model-based standard errors and confidence intervals. The registry does not report the observed distribution of the inter-limb ratio, group variances, diagnostic checks, transformations, or robust methods. There is therefore no basis in the record to assess those assumptions for this endpoint.

These methodological principles explain what a complete analysis would help readers assess; they do not supply missing trial results. The registry identifies the endpoint, its stated summary format, the intervention groups, and the assessment time. It does not report the primary estimates, statistical test, detailed analysis method, or relevant diagnostics.

10. Multiplicity, Missing Data and Analysis Populations

The trial includes a primary outcome and a range of secondary outcomes. The secondary outcomes listed in the registry cover extracellular fluid in the upper limb; ultrasound measurements of cutis and subcutis thickness of the arm and trunk; functioning related to BCRL; tissue elasticity; quality of life; erysipelas episodes; and overall and MLD-specific treatment satisfaction. The record reports 14 outcome measures in total, but it does not give a complete analysis account for those measures.

In general, testing many outcomes or multiple time points creates a multiplicity issue: the chance of at least one apparently notable result can rise when many comparisons are examined. Statistical plans may address this by defining a hierarchy, adjusting inference, or identifying exploratory analyses. The registry does not report whether any multiplicity procedure was planned or used, which outcomes were confirmatory, or how the different time points were handled. No adjustment should be assumed.

The primary endpoint description refers to the ratio at different time points, and the registry indicates that the primary outcome has several categories or time points rather than a single comparison reduced for reporting. No primary comparison is reported. The record also lists no analyses, so it does not provide an analysis population, model specification, or details of the estimand for the primary endpoint.

For missing data, the registry reports 5 dropouts by the post-intensive assessment, including 4 patients (2%) lost to follow-up. It does not report their group distribution, reasons for all dropouts, how missing measurements were treated, or whether sensitivity analyses were conducted. It is also not reported in the registry record whether analyses followed an intention-to-treat principle, included only participants with observed measurements, or used another population definition. These omissions limit assessment of attrition and the robustness of any outcome estimate.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group. The numbers at risk for serious adverse events were 63 for fluoroscopy-guided MLD, 63 for traditional MLD, and 64 for placebo MLD. The record also reports zero deaths in each group. These are the counts recorded during the trial; they do not establish that no unrecorded or unreported events occurred.

Other adverse events were reported for 5 participants in the fluoroscopy-guided MLD group, 8 in the traditional MLD group, and 7 in the placebo MLD group. The registry does not specify the event terms, severity, timing, or whether individuals could contribute more than one event. It also does not provide exposure-adjusted rates or a statistical comparison. The counts should therefore be read as descriptive entries, not as evidence that one group had a higher or lower risk.

In general, a safety comparison needs clear event definitions, follow-up coverage, participant exposure, and uncertainty around group estimates. The registry does not report those details for these adverse-event figures. The absence of recorded serious events in the listed groups is distinct from a demonstration that the groups have equivalent safety.

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

The registry record describes a randomized comparison of fluoroscopy-guided MLD, traditional MLD, and placebo MLD within a broader decongestive lymphatic therapy program. It identifies the primary outcome as the arm/hand inter-limb ratio after 3 weeks of intensive treatment and explains how the ratio is measured. It also records enrollment of 194 and reports limited information about losses by the post-intensive assessment.

What the record does not provide is the primary outcome result: no group means, confidence intervals, between-group estimates, or primary statistical test are reported. As a result, the direction and size of any differences, and the precision with which they were estimated, cannot be described. The record likewise does not establish whether the groups were similar at baseline or how missing primary measurements were handled.

These omissions matter because the existence of a randomized design and a specified endpoint is not itself evidence of an effect. In general, an estimate and its uncertainty are needed to judge how compatible the observed data are with different possible group differences. A p-value alone, if available, would not express the size or practical importance of a difference; in this record, neither the p-value nor the estimate is reported.

The adverse-event entries offer descriptive counts, including zero serious adverse events and zero deaths in each group, but do not provide enough detail for a comparative safety assessment. The secondary outcomes broaden the questions considered by the study, yet their results and analysis methods are not reported in the registry record.

Accordingly, the available information is useful for understanding the trial's design, treatment schedule, endpoint definition, and selected safety counts. It does not establish whether any MLD approach produced a larger or smaller change in lymphoedema volume, whether any difference was precise, or how the approaches compare on the secondary outcomes. Those questions require outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, this trial is notable for comparing three MLD approaches while keeping a broader set of care components in each arm description. That structure makes the assigned MLD approach the stated point of contrast within a program that also includes information, skin care, compression therapy, and exercises. It also makes careful description of the placebo procedure and shared treatment delivery important for interpreting what a group comparison would represent; those procedural details are not reported in the registry record.

The endpoint is a relative arm/hand volume measure, not simply an isolated measurement of the affected limb. Its construction incorporates measurements from both sides and a correction for hand dominance. This gives readers a clear account of the intended outcome but also highlights why measurement procedures and endpoint estimates matter. Without the group summaries and uncertainty intervals, the endpoint definition alone cannot answer the comparative question.

The trial also illustrates the distinction between a completed trial record and a posted results account. The registry lists enrollment, the treatment schedule, outcome measures, and selected adverse-event counts, but does not report a primary statistical analysis. The absence of outcome estimates means that readers cannot assess effect size, precision, or consistency across outcomes from this record.

Finally, the specified post-intensive assessment focuses attention on an early endpoint in a schedule that continues through maintenance and follow-up. Results at that assessment would address the primary question at that time, while results from later assessments could address durability or other changes. The registry describes the longer schedule but does not report those outcome results. Distinguishing the assessment time from the full treatment and follow-up period is essential to interpreting what the primary endpoint was designed to capture.

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.

A central limitation of the available record is the absence of primary outcome estimates and statistical comparisons. Although the endpoint is defined as an arm/hand inter-limb ratio after 3 weeks of intensive treatment, group means and 95% confidence intervals are not reported. The record therefore cannot show the direction, magnitude, or precision of the group differences.

The registry notes that 5 patients dropped out by the post-intensive assessment and that 4 patients (2%) were lost to follow-up. It does not state the treatment groups involved, reasons for all losses, or how missing endpoint measurements were handled. The extent to which missingness could affect the primary comparison cannot be assessed.

The registry's masking descriptions differ: the design field says triple masking, while the brief summary calls the study double-blinded. It does not explain the roles or procedures behind either description. Randomization procedures and allocation concealment are also not reported. These limits prevent assessment of how assignment and masking were implemented.

Although the record lists 14 outcome measures and several secondary outcomes, it does not provide results, a multiplicity approach, or a complete analysis plan. The primary endpoint is described across different time points, but a single primary comparison is not reported. The registry also does not report the trial's own sample-size justification, detailed outcome distributions, or diagnostic checks for the statistical assumptions.

Finally, the other adverse-event counts are not accompanied by event descriptions, severity, or exposure-adjusted comparisons. The listed serious-event and death counts are descriptive and cannot resolve these broader safety limitations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL — NCT02609724.
• Registry record last updated 2022-03-17; status last verified 2022-03.
• Results first posted 2022-03-07.
• 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

NCT02609724 is a completed randomized, parallel-group trial of fluoroscopy-guided MLD, traditional MLD, and placebo MLD for breast cancer-related lymphoedema. The registry records triple masking, while the brief summary describes the trial as double-blinded. Enrollment was 194, and the listed sponsor is Universitaire Ziekenhuizen KU Leuven. The start date was 2016-01 and primary completion was 2020-03.

Each arm description includes information, skin care, compression therapy, and exercises, with 3 weeks of intensive treatment, 6 months of maintenance treatment, and 6 months of follow-up. The primary endpoint is the arm/hand inter-limb ratio after intensive treatment. The registry reports 5 dropouts by that assessment, including 4 patients (2%) lost to follow-up.

The record does not report primary outcome estimates, statistical comparisons, or the analysis methods used. It lists zero serious adverse events and zero deaths in each group, as well as other adverse-event counts of 5, 8, and 7 across the three groups.