Urodynamic and Clinical Efficacy of Mirabegron for Neurogenic Bladder Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Urodynamic and Clinical Efficacy of Mirabegron for Neurogenic Bladder Patients (NCT02044510), a randomized phase 2, phase 3 study. The primary outcome is Bladder Capacity.

2. Clinical Question

The trial asked whether mirabegron changed urodynamic bladder capacity in adults with neurogenic bladder compared with placebo. The registry describes a planned study in patients with multiple sclerosis or spinal cord injury and a primary outcome of increased urodynamic bladder capacity. Posted results report least-squares mean capacity at 10 weeks for the mirabegron and placebo groups.

The clinical question is narrower than whether symptoms or quality of life changed. The record lists additional outcomes, including voiding diary measures, urinary quality-of-life measures, patient-reported measures, adverse events, and other urodynamic characteristics. Those outcomes address related aspects of bladder function, but the posted primary result concerns bladder capacity in mL.

3. Trial Design

The registry describes a randomized, parallel-group, placebo-controlled trial with quadruple masking. It lists Phase 2 and Phase 3 and identifies the sponsors as London Health Sciences Centre Research Institute or Lawson Research Institute of St. Joseph's. The study status is terminated. The recorded start is 2014-07, and primary completion is recorded as 2018-01.

The planned design described in the registry summary was a multicenter study lasting 12 weeks, including a 1-4 week run-in without active treatment or placebo. The treatment description assigns mirabegron 25mg daily for two weeks followed by 50mg daily for eight weeks, or matching placebo with placebo escalation. The summary says that treatment arms would be stratified according to whether participants were already taking an anticholinergic medication. Whether that stratification was implemented is not reported in the registry record.

The registry summary describes a planned total of 144 participants, with 72 assigned to placebo and 72 to mirabegron. Recorded enrollment is 32, and the posted primary endpoint results show 16 participants in each arm. These figures describe different aspects of the record: planned enrollment in the study summary, recorded enrollment, and the group counts attached to the posted primary result. The reason enrollment was lower than planned is not reported in the registry record.

The primary outcome is urodynamic bladder capacity at 10 weeks. The summary describes urodynamic measurements near enrollment and at the end of study. The posted endpoint is presented as a least-squares mean with a 95% confidence interval. Specific analysis-population definitions, the statistical model behind the least-squares means, and details of any protocol changes 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:

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 Bladder Capacity, measured over 10 weeks.

The primary endpoint is urodynamic bladder capacity, measured in mL at 10 weeks. It describes the volume recorded during urodynamic assessment and is a direct measure of bladder capacity under the study's testing conditions. The registry summary identifies an increase in capacity as the intended primary outcome. That stated hypothesis explains the endpoint's role in the trial; it does not establish that an increase occurred or that any observed difference was caused by treatment.

The posted results give a least-squares mean for each group, together with a 95% confidence interval. A least-squares mean is a model-based estimate, rather than necessarily the simple arithmetic average of the individual measurements. The registry record does not report the model specification or covariates, so the adjustments used to obtain these means are not clear from the record.

Urodynamic capacity is one part of bladder function. It does not by itself describe symptoms, quality of life, voiding patterns, or adverse effects. The registry lists other outcome measures intended to address some of those dimensions, but the primary result should be interpreted as a measurement of capacity at the stated assessment time, not as a complete account of clinical experience.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary results are continuous measurements, reported in mL. The registry describes each arm's result as a least-squares mean and gives a 95% confidence interval. Several statistical ideas help distinguish what these summaries show from what they do not establish.

What does a least-squares mean represent?

A least-squares mean is generally a model-based estimate of a group mean. Depending on the analysis, it may account for other variables or features of the design. It can differ from a simple arithmetic mean of the observed measurements. The registry record does not report the model, included covariates, or estimation procedure, so the exact interpretation of these particular least-squares means cannot be reconstructed from the posted record. They should be described using the registry's label rather than assumed to be unadjusted averages.

How should the confidence intervals be read?

A confidence interval expresses uncertainty in an estimate using a method with a stated long-run coverage property, assuming the method's conditions hold. In repeated use of the same procedure under its assumptions, intervals constructed in this way would contain the underlying quantity at the stated rate. For an individual study, the interval is not a probability statement that the true value lies within its particular endpoints. It conveys which values are reasonably compatible with the observed data and analysis, subject to the method's assumptions.

The mirabegron estimate is 305.0 mL, with a 95% confidence interval of 234.0 to 376.0 mL. The placebo estimate is 369.0 mL, with a 95% confidence interval of 298.0 to 440.0 mL. Each interval pertains to its own arm mean. A direct treatment comparison would ordinarily be expressed as an estimated contrast, such as the difference between group means, with its own uncertainty interval and possibly a test. None is posted in the registry record. The arm-specific intervals should not be treated as if they were the confidence interval for that contrast.

Why is a direct comparison important?

Randomization supports a comparison between assigned groups, but the statistical result needs to quantify that comparison. Separate arm means are useful descriptions; they do not tell the reader the uncertainty around the treatment contrast. A formal comparison can also reflect the analysis model and any planned adjustments. In this record, a p-value and an interval for the between-arm effect are not reported. No statistical significance conclusion can be drawn from the two arm estimates alone.

What does the small posted group size imply?

The endpoint results include 16 participants in each group. With a limited number of observations, estimates can be sensitive to the measurements contributed by individual participants, and uncertainty may remain substantial. The confidence intervals are the posted indication of uncertainty for each mean. The record does not include individual observations or additional distributional summaries, so the shape of the outcome distribution and the influence of unusually high or low values cannot be assessed from the posted results.

General statistical consideration: continuous outcomes may be analyzed using methods that assume a particular distribution or variance structure. If observations vary more than the model allows, standard errors and confidence intervals can be miscalibrated; this is one reason model diagnostics and clear analysis reporting matter. The registry record does not report such diagnostics, whether variance assumptions were checked, or whether an alternative method was used.

What can planning calculations tell readers?

General statistical consideration: a sample-size calculation depends on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is retrospective and hypothetical; it does not establish the probability that the completed trial detected an effect. It is not observed power, and it does not replace the missing treatment-effect estimate or its uncertainty. The record's planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It is explicitly not the trial's own design calculation.

The study summary's planned total enrollment is 144, while recorded enrollment is 32. The registry does not report a sample-size justification, the assumptions behind the original target, or a revised target after enrollment. It is not appropriate to infer a design rationale from the planning illustration, which is distinguished in the record from the original trial design.

What is not reported about the analysis?

The record reports zero analyses and does not provide a formal primary comparison. It does not report the statistical model, analysis population, missing-data method, baseline adjustment, multiplicity strategy, or sensitivity analyses. These omissions limit reproducibility and make it difficult to assess whether the posted group means answer the originally planned hypothesis in the intended way. Statistical interpretation should remain limited to the endpoint summaries and uncertainty intervals that are actually posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and posts 12 secondary outcomes in addition to the primary endpoint. These include a 3 Day Voiding Diary, 24hr Urinary Pad Weights, bladder-specific and incontinence quality-of-life measures, patient-reported measures, adverse events, and secondary urodynamic characteristics. Considering multiple outcomes can raise the chance of finding at least one apparently notable result by chance when many tests are performed. Whether and how that issue was addressed is not reported in the registry record.

The record does not report a prespecified multiplicity procedure, a hierarchy of outcomes, or which secondary outcomes were confirmatory versus exploratory. It also reports zero analyses, so no secondary-outcome effect estimates or tests are available in the posted analysis information. The presence of outcome names alone does not show that results were collected, analyzed, or interpreted according to a particular plan.

Missing-data handling is also not reported in the registry record. Although 16 participants appear in each arm's primary endpoint result and recorded enrollment is 32, the record does not describe assessment completion, exclusions, withdrawals, or how missing measurements were treated. It does not specify whether the analysis followed an intention-to-treat principle, a per-protocol definition, or another analysis population. Equal group counts do not establish that all randomized participants had complete outcome data or that no observations were excluded.

The record also does not report a statistical analysis plan, sensitivity analyses, or procedures for handling protocol deviations. These are important for understanding which analyses were intended and how robust the findings are to reasonable alternatives. Without these details, readers should not assume that missing outcomes were absent, that a particular method was used, or that multiple comparisons were controlled.

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.

The posted safety figures list 16 participants at risk in each arm. Serious adverse events affected 0 participants in the mirabegron group and 0 in the placebo group. Other adverse events affected 0 participants in each group, and deaths were 0 in both groups.

These are counts in the posted registry results, not proof that no adverse events occurred outside the recorded categories or reporting period. The registry record does not explain the methods used to collect or classify adverse events, the length of safety follow-up, or whether all participants completed safety assessment. It also does not provide event-level descriptions in the serious adverse event list, which is empty.

Zero recorded events in these groups should be interpreted in the context of the number of participants and the information reported. A small group with no recorded events cannot precisely characterize uncommon harms. The figures are descriptive and do not support a broad comparison of safety risks or a conclusion about safety in populations beyond the participants represented in the record.

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

The posted primary outcome results describe urodynamic bladder capacity at 10 weeks. They report a least-squares mean of 305.0 mL in the mirabegron arm and 369.0 mL in the placebo arm, each based on 16 participants, with a 95% confidence interval for each arm mean. These are the observed registry summaries, not a reported treatment-effect estimate.

The record does not post a direct comparison between groups, a confidence interval for the contrast, or a p-value. It therefore does not establish how precisely the groups differed, whether any difference met a statistical criterion, or whether the result was consistent with the trial's stated hypothesis. No conclusion that mirabegron works or does not work follows from the two group means alone.

The record also does not provide enough analysis detail to determine the model behind the least-squares means, what participants were included in the analysis, or how missing outcomes were handled. Nor does it explain why the trial was terminated or how that status affected conduct and outcome reporting. Those gaps restrict interpretation of the endpoint summaries.

The registry includes multiple secondary outcomes, but does not report analyses for them. As a result, the posted primary summaries do not describe symptom scales, quality of life, diary outcomes, or the broader set of urodynamic measures. The posted safety counts report no serious adverse events, other adverse events, or deaths in either arm, but the limited group size and unspecified safety methods constrain what those zero counts can establish.

Overall, the result is best treated as a limited descriptive record of group-specific capacity estimates. It is not a complete statistical evaluation of the randomized comparison, and it does not by itself provide a basis for clinical decisions.

13. Why This Trial Matters Statistically

This trial illustrates a distinction that matters in clinical biostatistics: reporting results for each randomized arm is not the same as reporting the randomized treatment comparison. The least-squares means and their confidence intervals describe capacity estimates within each group. Without an estimated between-group contrast and its uncertainty, readers cannot directly evaluate the primary comparative question.

The record also puts the size of the available endpoint data in context. It describes a planned total of 144 participants, while recorded enrollment is 32 and the primary results include 16 per arm. The reason for the difference is not reported. This makes it especially important to distinguish the original plan from the participants represented in the posted endpoint results, rather than infer a design change or explanation.

The trial's listed outcomes span urodynamic measurements, symptoms, voiding diaries, quality of life, and safety. Such a broad set can address more than one dimension of an intervention's effects, but it also makes transparent reporting of the analysis plan and multiplicity approach important. Neither is reported in the registry record, and no analyses are posted.

Finally, the zero event counts demonstrate why safety summaries need context as well as counts. When group sizes are limited, no recorded events are informative as a description of these participants but cannot precisely characterize uncommon outcomes. Taken together, this record is a useful example of how endpoint definition, direct contrasts, uncertainty, missing-data reporting, and trial status all shape the interpretation of registry results.

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 record's primary results are limited to arm-specific least-squares means and confidence intervals. No treatment contrast, p-value, or analysis results are posted, even though the study summary states a comparative hypothesis. The model used to produce the least-squares means is not described, limiting interpretation and reproducibility.

Recorded enrollment is 32, while the planned total in the registry summary is 144. The reason for the difference is not reported in the registry record. The trial is marked terminated, but the reason for termination and whether it affected the timing or completeness of assessments are not reported. These details should not be inferred from the status alone.

The record does not identify the analysis population, explain whether all randomized participants were analyzed, or describe missing-data handling, exclusions, withdrawals, or protocol deviations. It also does not report whether baseline capacity was included in the model, whether the stated stratification by anticholinergic use was implemented, or whether diagnostic checks and sensitivity analyses were performed.

Multiplicity procedures and a statistical analysis plan are not reported. Although many outcome measures are listed and secondary outcomes are posted, analyses are not reported. Therefore, the record does not allow an assessment of how the primary endpoint was prioritized relative to other outcomes or whether all planned outcomes were analyzed.

Safety results list zero serious adverse events, other adverse events, and deaths in both arms, but safety assessment methods and follow-up completeness are not described. The small posted group counts limit the information available about uncommon events. These limitations do not invalidate the posted summaries, but they restrict the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Urodynamic and Clinical Efficacy of Mirabegron for Neurogenic Bladder Patients — NCT02044510.
• Registry record last updated 2019-02-05; status last verified 2019-01.
• Results first posted 2019-01-07.
• 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

NCT02044510 is a randomized, parallel, placebo-controlled trial listed as Phase 2 and Phase 3 and marked terminated. The registry records enrollment of 32. Its planned study summary describes mirabegron compared with matching placebo in adults with neurogenic bladder, with a primary outcome of urodynamic bladder capacity.

At 10 weeks, the posted least-squares mean capacity was 305.0 mL for mirabegron and 369.0 mL for placebo, with 16 participants in each arm and a 95% confidence interval for each mean. The registry record does not report a formal between-arm analysis. No serious adverse events, other adverse events, or deaths are posted in either group. The reason for termination, the analysis population, missing-data methods, and statistical analysis plan are not reported in the registry record.