Combined Treatment for Mixed Incontinence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined Treatment for Mixed Incontinence (NCT01959347), a randomized phase 3 study. The primary outcome is Change From Baseline UDI Total Score.

2. Clinical Question

3. Trial Design

ESTEEM was a randomized, parallel-group, phase 3 trial. Its registered comparison assigned participants to midurethral sling surgery alone or to sling surgery combined with behavioral and pelvic floor therapy. The record identifies the trial as single-masked but does not specify who was masked. It lists the sponsor as the NICHD Pelvic Floor Disorders Network.

The registered trial start date was 2013-10-28, and the primary completion date was 2017-08-09. The study status is completed. The enrollment field reports 480; the brief summary describes the treatment objective in 472 women. The record does not explain the difference between these figures, so they should not be treated as interchangeable descriptions of the analyzed population.

The brief summary describes the central aim as estimating the effect of combined treatment compared with sling surgery alone on successful treatment of mixed urinary incontinence symptoms. It also lists secondary aims concerning overactive bladder and stress urinary incontinence outcomes, additional treatment, time to failure, and predictors of poor outcomes. The registered primary outcome, however, is change from baseline in UDI total score at 3, 6, and 12 months.

The registry describes an intent-to-treat analysis that included eligible randomized participants who provided outcome data after baseline. Data collected after retreatment for urinary incontinence were excluded. Further details about randomization procedures, masking implementation, allocation concealment, and the statistical analysis plan 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: An intent-to-treat (ITT) analysis which included all eligible participants who were randomized and who provided outcome data after baseline was performed. Data that was collected after a participant was retreated for urinary incontinence was excluded from the analysis.

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 Change From Baseline UDI Total Score, measured over 3, 6, and 12 Months.

The primary outcome was change from baseline in the Urogenital Distress Inventory total score, reported as a mean in units on a scale. The registry specifies assessment at 3, 6, and 12 months. The UDI is described as a standardized measure of overactive bladder symptoms and health-related quality of life. Its range is 0 to 300, with higher scores indicating greater distress.

Change was defined as the score at a follow-up visit minus the baseline score. Given that definition and the score direction, a negative change represents a lower score relative to baseline, while a positive change represents a higher score. This interpretation concerns score direction only; without numerical outcome estimates, it does not indicate what happened in either treatment arm.

A total score can summarize distress across the measure rather than focusing on one symptom domain. The record also lists separate secondary outcomes for changes in UDI stress, irritative, and obstructive scores. These are distinct outcomes and should not be substituted for the registered primary total score. The registry record does not report numerical primary outcome estimates or confidence intervals at the specified visits, so the size and precision of any between-group difference cannot be described from the available outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is randomized and parallel-group: participants were allocated to one of two treatment strategies, and the arms were followed as separate groups. Randomization is generally used to reduce systematic differences between groups at assignment. It does not guarantee that every characteristic is balanced, and it does not replace clear reporting of how the allocation sequence was generated or concealed. Those procedural details are not reported in the registry record.

The registered primary endpoint is continuous: it is a score, and the summary measure is the mean. For each participant with eligible data, change is defined as follow-up score minus baseline score. A group mean describes the average change among the participants included in the analysis; it does not describe every participant’s individual experience. The record specifies the UDI scale range and direction, which are important for interpreting the sign and magnitude of any reported change.

A between-group estimate would address the contrast between the two treatment strategies. A confidence interval would express uncertainty around that estimate. In general, the interval’s width reflects how precisely the effect is estimated under the analysis; the interval should be considered along with the point estimate rather than treated as a separate result. No primary estimates or confidence intervals for the registered visits are reported in the registry record, so these quantities cannot be interpreted for this trial from the information described.

The registry specifies an intent-to-treat analysis including eligible participants who were randomized and had outcome data after baseline. This description defines the intended analysis population, while also making clear that participants without post-baseline outcome data are not included in that stated population. The record further says that observations collected after a participant was retreated for urinary incontinence were excluded. It does not explain how missing values were handled, how many participants contributed data at each visit, or whether sensitivity analyses assessed the impact of missing data or retreatment.

The primary outcome is listed at multiple follow-up times. In general, testing several outcomes or time points can increase the chance of finding at least one apparently notable result by chance if each is interpreted independently. Statistical approaches to address this issue can include prespecified testing hierarchies or adjustments to significance thresholds. The registry record does not report a multiplicity strategy, a hierarchy among the primary time points, or a statistical analysis plan. The existence of multiple registered outcomes does not by itself tell readers which comparisons were formally tested or how their interpretation was controlled.

The registry describes the trial as single-masked, but does not identify who was masked or how masking was maintained. This limits interpretation of the practical safeguards against knowledge of treatment assignment influencing treatment delivery, outcome assessment, or reporting. The record does not give additional details about the masking procedure.

Sample-size planning and results should be distinguished. The planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. Such a calculation is a planning exercise, not observed power and not an outcome of the randomized comparison. The record does not report the trial’s own sample-size justification. It also does not report numerical primary estimates in the registry record, so no observed-effect-based planning values can be interpreted from the information described.

General statistical context: over-dispersion matters when count data vary more than a model’s assumed distribution allows, because standard errors and uncertainty estimates can then be misleading if the extra variation is ignored. That concept does not establish that over-dispersion was relevant to this trial. The registered primary outcome is a continuous score summarized by a mean, and the registry information described does not report an over-dispersion analysis or a model for the primary outcome.

General statistical context: a treatment estimate and its uncertainty answer different questions. The estimate describes the observed contrast under a specified analysis, while its uncertainty reflects the precision of that estimate. Neither a statistically significant test nor a confidence interval alone establishes clinical importance. Interpretation also depends on the outcome’s scale, the estimate’s size, the analysis population, missing-data handling, and the prespecified plan. The registry record does not report enough numerical primary-outcome information to make those judgments for this comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome at 3, 6, and 12 months, as well as secondary outcomes for changes in UDI stress, irritative, and obstructive scores. The brief summary also describes additional secondary objectives. Multiple outcomes and follow-up times create a multiplicity question: if many comparisons are tested, the chance of at least one result appearing notable by chance can rise. General approaches include prespecifying a primary comparison, setting an order for testing, or adjusting inference across comparisons. Which approach, if any, was used is not reported in the registry record.

The record does not provide a statistical analysis plan, adjustment method, or a stated hierarchy for the primary time points. The registry lists 50 outcome measures and reports no analyses in its analysis information. Those details do not establish that analyses were not performed; they mean that analysis details and numerical results are not reported in the registry record.

The described analysis population included eligible randomized participants with outcome data after baseline. Data collected after retreatment for urinary incontinence were excluded. Missing-data methods, counts with outcome data at each visit, reasons for missingness, and sensitivity analyses are not reported in the registry record. These omissions matter because the available observations may not represent all randomized participants if data availability is related to treatment or outcome.

The stated intent-to-treat label should therefore be read alongside the eligibility and outcome-data requirements and the exclusion of post-retreatment data. The record does not explain whether all randomized participants met the analysis criteria or how deviations from the assigned treatment were handled. These details are necessary to assess fully how closely the analysis reflects the randomized comparison.

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 0.00% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatitis acute (1.3%), gastritis (0.8%), pyelonephritis (0.8%), bladder neck suspension (0.8%), cellulitis (0.8%).

The safety information reports serious adverse events for two groups. In the “MUS Only” group, 28 participants were affected among 238 at risk; in the “MUS+BPTx” group, 21 were affected among 242 at risk. The record reports deaths as 0 in each group. It also reports other adverse events for 163 among 238 at risk in the sling-only group and 172 among 242 at risk in the combined-treatment group.

These are counts with their corresponding numbers at risk, not estimates of a causal treatment effect. No comparative confidence intervals or statistical tests for the safety figures are reported in the registry record. The record does not describe how event episodes were counted, whether an individual could contribute more than one event, or the observation period used for these safety summaries. The counts alone therefore should not be interpreted as a complete comparison of risk.

The registry lists acute pancreatitis at 1.3%, and gastritis, pyelonephritis, bladder neck suspension, cellulitis, and asthma at 0.8% each among the top serious-event terms. These selected terms do not describe every event or establish that a particular event was caused by treatment. The safety figures are separate from the primary UDI outcome and do not provide evidence about symptom-score changes.

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

The registry record establishes that ESTEEM was designed as a randomized comparison of sling surgery alone with sling surgery plus behavioral and pelvic floor therapy for mixed urinary incontinence. It defines the primary outcome, the score direction, and follow-up at 3, 6, and 12 months. It also gives the stated analysis-population criteria and selected safety counts. These details describe the question and some features of the study conduct.

They do not establish the magnitude or direction of the primary treatment contrast. The numerical UDI total-score changes and between-group estimates are not reported in the registry record. Without those estimates and their uncertainty, readers cannot determine how much the groups differed on the primary outcome or how precisely that difference was estimated. The absence of numerical results in this record is not itself evidence that there was no difference.

The record’s secondary aims and outcome listings also do not establish findings for those questions. The reported safety counts are descriptive information, not a substitute for an adjusted or otherwise specified comparison, and the selected serious-event terms do not by themselves establish causation. Likewise, the completed study status does not indicate whether a particular clinical outcome favored either strategy.

General interpretation: a trial result is specific to its population, treatment strategies, outcome definitions, follow-up, and analysis. A score change can be statistically distinguishable from no difference yet have uncertain practical importance, or it can be imprecisely estimated. The appropriate assessment depends on the observed estimate, its confidence interval, and relevant clinical context. Those numerical primary results and any clinical-importance threshold are not reported in the registry record.

Accordingly, the record supports a description of the randomized research question and the planned outcome framework, but not a conclusion about the comparative effect on UDI total score. It also does not support a recommendation about treatment. Interpretation of the primary question requires numerical results and analysis details beyond those reported in the registry record.

13. Why This Trial Matters Statistically

This trial’s statistical question is not simply whether two procedures were compared. It asks whether adding behavioral and pelvic floor therapy to midurethral sling surgery changes a patient-reported score for distress associated with urinary symptoms. The randomized, parallel-group design is relevant because it frames the comparison between treatment strategies, while the repeated follow-up times make clear that the outcome is assessed over more than one point in time.

The endpoint definition matters. The UDI total score has a stated direction, and change is defined relative to baseline. Without both details, a change estimate could be misread. The registry also lists separate stress, irritative, and obstructive score changes, illustrating that a total score and symptom-domain outcomes address related but distinct questions.

Multiplicity and missing data are important to this kind of outcome framework. Several follow-up times and outcomes can complicate interpretation unless the analysis plan establishes which comparisons are primary and how uncertainty is handled. Requiring post-baseline data and excluding observations after retreatment also makes the analysis population and missing-data approach consequential. The registry does not report the details needed to evaluate those issues fully.

The safety information illustrates another statistical distinction: descriptive counts are not the same as a comparative estimate with uncertainty. Counts can be useful for describing events, but their interpretation depends on definitions, follow-up, and the analysis approach. The registry’s selected event terms and group counts should not be conflated with the primary symptom endpoint.

Finally, a completed randomized trial and a defined primary outcome do not, by themselves, allow quantitative conclusions. Statistical interpretation depends on the actual effect estimate, its precision, and the analysis choices. Those primary outcome results are not reported in the registry record, making transparent outcome reporting central to understanding this comparison.

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 most consequential limitation for interpreting the registered primary question is that numerical results for the primary outcome are not reported in the registry record. There are no listed mean changes or between-group estimates at 3, 6, or 12 months, and no confidence intervals for those comparisons in the information described. The effect’s direction, size, and precision therefore cannot be assessed from this record.

The record also does not provide a statistical analysis plan, multiplicity strategy, detailed missing-data methods, or the number of participants contributing outcome data at each follow-up. Because the stated analysis included participants with post-baseline data and excluded data after retreatment, additional detail would be needed to understand how the analysis population changed over time and how those decisions affected the estimates.

Masking is described as single, but the record does not identify who was masked or explain the procedure. Randomization methods and allocation concealment are also not described. The record does not report how treatment adherence, deviations, or retreatment were handled beyond the exclusion of post-retreatment observations from the analysis.

Enrollment is reported as 480, while the brief summary describes 472 women in its account of the treatment objective. The record does not reconcile these figures or specify their relationship to the analyzed population. Safety information includes group counts and selected serious-event terms, but does not report comparative uncertainty or the event-counting and observation details needed for fuller interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combined Treatment for Mixed Incontinence — NCT01959347.
• Registry record last updated 2020-05-14; status last verified 2020-05.
• Results first posted 2020-05-14.
• 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

ESTEEM was a completed, randomized, parallel-group, phase 3 trial comparing midurethral sling surgery alone with sling surgery plus behavioral and pelvic floor therapy for mixed urinary incontinence. The registry describes the study as single-masked. Its primary outcome was change from baseline in UDI total score at 3, 6, and 12 months; higher scores indicate greater distress.

The record specifies an intent-to-treat analysis of eligible randomized participants with post-baseline outcome data and exclusion of data collected after retreatment for urinary incontinence. It reports enrollment as 480, while the brief summary describes 472 women, without explaining the difference. Serious-event counts, other-event counts, and deaths are reported by group. Numerical primary outcome estimates, confidence intervals, and further statistical-plan details are not reported in the registry record.