Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder (NCT00439140), a randomized phase 3 study. The primary outcome is Change From Baseline in Forced Vital Capacity (FVC).

2. Clinical Question

The study summary frames the clinical question around safety and efficacy of botulinum toxin Type A for urinary incontinence associated with overactive bladder in people with spinal cord injury or multiple sclerosis. The registry describes a randomized, parallel-group, quadruple-masked phase 3 trial. Its stated primary measure, however, is FVC rather than a bladder symptom measure. FVC is the maximum amount of air exhaled after taking the deepest breath possible, and the registry says a positive change from baseline indicated improvement.

Other registered outcomes include change from baseline in urinary incontinence episodes, maximum detrusor pressure, and maximum cystometric capacity. These measures address bladder symptoms or function, while FVC measures respiratory function. The registry record does not report why FVC was selected as the primary endpoint or how it was intended to relate to the study’s broader clinical question.

The listed treatment schedules include active treatment and placebo on Day 1, with later injections described as applicable after a minimum of 12 weeks. The registry does not provide a single posted comparison of the primary endpoint, so the direction, size, and precision of any treatment difference cannot be described from the record.

3. Trial Design

This was a phase 3, randomized, parallel-group trial with quadruple masking. The registry lists enrollment of 41 and identifies Allergan as the sponsor. The study status is terminated. The start date is 2007-06, and the primary completion date is 2012-12. The reason for termination is not reported in the registry record.

The intervention descriptions specify botulinum toxin Type A injections into the detrusor. They include a 200U regimen and a 300U regimen on Day 1, each followed by a repeat injection after a minimum of 12 weeks if applicable. Placebo schedules describe Normal Saline injection into the detrusor on Day 1 followed by active treatment after the same minimum interval if applicable. One placebo-to-300U description notes that the subsequent dose would be 200U after discontinuation of 300U. The registry does not report the allocation ratio, the reason for the dose schedules, or the circumstances that determined whether a repeat injection was applicable.

Randomization is intended, in general, to reduce systematic differences between treatment groups at the point of assignment. Masking can reduce the influence of treatment knowledge on care or assessment, although the registry does not identify which roles were masked or explain how masking was maintained. A parallel-group design assigns participants to a treatment schedule that is followed alongside the other schedules, rather than describing a crossover between treatments.

The safety results use groups titled Botulinum Toxin Type A 200U, Botulinum Toxin Type A 300U, and Placebo/Botulinum Toxin Type A. The registry’s safety group labels do not separately show the placebo-to-200U and placebo-to-300U schedules described in the intervention information, so the record does not establish how those schedules map to the safety groups. It also does not report group-specific enrollment or the number randomized to each schedule.

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: Botulinum toxin Type A 300U was discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) received botulinum toxin Type A 200U instead.

Treatment Cycle 1

Reasons for not completing this period:

Treatment Cycle 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population included all randomized participants who received treatment.

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 in Forced Vital Capacity (FVC), measured over Baseline, Week 6.

The primary endpoint is change from baseline in forced vital capacity (FVC), measured in liters at baseline and Week 6. FVC is the maximum amount of air exhaled after a person takes the deepest breath possible. The registry states that spirometry followed American Thoracic Society standards and that a spirometer was used for measurement. It also defines a positive change from baseline as indicating improvement.

FVC is a continuous measure of respiratory function. In general, a continuous endpoint can describe both the direction and magnitude of change on a measurement scale. The registry lists the endpoint summary as a mean and its dispersion as a standard deviation. A mean describes the average observed measurement or change; a standard deviation describes variation among observations, not the precision of the mean itself.

The registry record does not report a numerical mean change, a standard deviation, or a treatment comparison for FVC. It also does not state why this respiratory measure was selected as the primary endpoint for a study whose summary focuses on urinary incontinence associated with overactive bladder. The endpoint’s measurement procedure and timepoints are described, but its clinical rationale and the posted results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as randomized, parallel-group, and quadruple-masked. In general, random allocation aims to make treatment groups comparable with respect to both measured and unmeasured characteristics on average, although chance imbalances can remain, especially in a small trial. A parallel-group design compares groups assigned to different schedules. Masking is intended to limit the effects of knowing treatment assignment, but the registry record does not identify the masked roles, the randomization procedure, or the method used to preserve masking.

What does the primary measure represent?

FVC is a continuous measurement in liters, collected at baseline and Week 6. The outcome is defined as change from baseline, with a positive change indicating improvement according to the registry description. In general, analysis of change compares a follow-up measurement with a baseline measurement for each participant, then summarizes those changes. The registry identifies the summary as a mean and the spread as a standard deviation. It does not provide the group means, standard deviations, or a treatment contrast, so the magnitude and precision of the observed change cannot be assessed.

A standard deviation describes how dispersed individual measurements or changes are around their mean. It is not the same as a confidence interval, which is a way to express uncertainty about an estimated quantity. General statistical interpretation of a treatment effect would consider both the estimated difference and its uncertainty; a small or large point estimate alone cannot show how precisely it was estimated. No confidence interval or other uncertainty measure for the primary comparison is reported in the registry record.

What can randomization and masking establish?

Randomization supports a comparison based on assigned treatment, but an interpretable randomized comparison also depends on how participants are analyzed, how missing measurements are handled, and whether outcome measurement is consistent. The record defines the Safety Population as all randomized participants who received treatment. It does not report how many participants from each group were in that population, how many completed the Week 6 measurement, or whether the primary endpoint was analyzed using another population. Quadruple masking is recorded, but the identities of the masked groups of people and any assessment of masking success are not reported in the registry record.

How should the absence of analysis results be understood?

The registry record reports zero analyses. This means that the record contains no posted statistical analysis results; it does not establish that no analyses were conducted elsewhere. The primary outcome is also flagged as having several categories or time points and not being reduced to one comparison. Although its description names baseline and Week 6, there is no single posted numerical comparison to interpret. The specific statistical model, any adjustment for baseline values, the treatment contrast, the handling of repeated measurements, and the approach to missing values are not reported in the registry record.

Why do outcome types matter?

FVC is continuous, so methods for continuous outcomes commonly summarize the location and spread of measurements and estimate a difference between groups. In general, assumptions about the distribution of measurements and the model used affect the interpretation of estimates and uncertainty. The registry names a mean and standard deviation but does not identify a test, model, or assumption checks.

Some listed outcomes have different statistical forms. Urinary incontinence episodes are counts over a measurement period, while detrusor pressure and cystometric capacity are measurements. In general, count data may show over-dispersion, meaning that variability exceeds what a simple count model assumes; accounting for it can be important for valid uncertainty estimates. The registry record does not report the modeling approach for these outcomes, the observation period for episode counts, or whether over-dispersion was assessed. No statistical method should be inferred from the outcome names alone.

The planning assumptions described in the registry concern illustrations based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, normal approximation, and detection of a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event illustrations are described as total event counts. These are planning illustrations, not observed power. The effect estimate used as their starting point and any sample-size justification for the original trial are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary FVC measure and secondary measures of urinary incontinence episodes, maximum detrusor pressure, and maximum cystometric capacity. Multiple outcomes or comparisons can raise a multiplicity issue: in general, testing many hypotheses can increase the chance of at least one apparently positive result by chance. A prespecified hierarchy or adjustment can help address that issue, but the registry record does not report a multiplicity strategy, a testing hierarchy, or a statistical analysis plan.

The primary endpoint entry refers to baseline and Week 6, while the registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. The record does not state which comparison would be primary if multiple comparisons were possible, nor does it provide analysis results for any of the listed outcome measures.

Missing-data handling is also not reported in the registry record. There is no description of how missing FVC measurements or missing secondary-outcome data were treated, whether participants with incomplete follow-up were included, or whether any sensitivity analyses were conducted. These details matter because analyses based on different assumptions about missing observations can produce different estimates.

The primary endpoint population is defined as the Safety Population, consisting of all randomized participants who received treatment. The record does not report the number analyzed for FVC or clarify whether this definition also applies to each secondary outcome. Enrollment of 41 is not a substitute for the number with an observed endpoint or the number included in a particular analysis. The registry reports zero analyses, so the analysis populations and missing-data procedures cannot be evaluated from posted results.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (14.3%), septic shock (8.3%), urinary tract infection pseudomonal (8.3%), urosepsis (8.3%), calculus ureteric (8.3%).

The registry reports serious and other adverse events for three safety groups. For serious events, the number affected and the number at risk are 4 of 15 for Botulinum Toxin Type A 200U, 6 of 14 for Botulinum Toxin Type A 300U, and 1 of 12 for Placebo/Botulinum Toxin Type A. For other adverse events, the corresponding counts are 12 of 15, 12 of 14, and 10 of 12. These figures describe participants affected in each listed group; they are not counts of all individual event episodes.

The serious-event terms and percentages listed in the record are urinary tract infection (14.3%), septic shock (8.3%), urinary tract infection pseudomonal (8.3%), urosepsis (8.3%), calculus ureteric (8.3%), and lower respiratory tract infection (7.1%). The registry does not specify a treatment group for each term in this listing, so these percentages should not be read as group-specific rates. The record also does not provide enough detail to determine event timing, recurrence, or how events were judged related to treatment.

These descriptive safety counts do not by themselves establish that a treatment caused an event or that groups differ reliably. The death entries are null; deaths are therefore not reported in the registry record, rather than confirmed as absent.

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

The record establishes that this was a randomized, quadruple-masked phase 3 trial of botulinum toxin Type A and placebo schedules in the stated neurogenic overactive bladder context. It identifies FVC change from baseline at Week 6 as the primary endpoint and lists bladder-related secondary measures. It also reports safety counts for three named groups. Those details describe the study’s design and the information registered, but they do not establish the size or direction of an efficacy effect.

No numerical primary-outcome comparison is reported. There is no mean FVC change by group, no estimated difference between groups, and no uncertainty interval or p-value in the registry record. The record consequently cannot show whether any observed difference was small or large, precise or imprecise, or compatible with a range of possible effects. The absence of posted results should not be interpreted as evidence of no effect.

The safety counts are descriptive and do not resolve causal questions. The groups are small in the context of the reported enrollment, and the registry does not provide an adjusted comparison, an account of event timing, or a group assignment for each listed serious-event term. These data should not be used alone to infer comparative safety.

More broadly, statistical significance and clinical importance are different concepts. In general, significance tests address compatibility with a statistical null under a specified model, while clinical importance requires judging the size and relevance of an effect in context. Neither judgment can be made for the primary endpoint from the posted record because its numerical results and analysis details are not reported. The trial’s terminated status also does not explain the missing analysis results; the reason for termination is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry record’s design information and its statistical results need to be read separately. Randomization, parallel groups, and quadruple masking describe features intended to support a fair comparison. They do not supply the endpoint estimates, uncertainty measures, or analysis details needed to assess the evidence for a treatment contrast. Here, the registry identifies a primary endpoint and a defined safety population, but reports zero analyses.

The choice and interpretation of the endpoint also matter. The study summary focuses on urinary incontinence associated with overactive bladder, while the registered primary outcome is FVC. The registry describes the FVC measurement procedure and how to interpret the direction of change, but does not report why this measure was selected as primary. Without that rationale or a numerical comparison, readers cannot judge how the primary result would relate to the study’s stated clinical focus.

The record also demonstrates the importance of keeping safety summaries distinct from efficacy analyses. Counts of participants affected by adverse events can describe what was registered in each safety group, but they do not quantify a reliable causal difference. Group sizes and event counts alone do not provide the uncertainty around a comparative effect.

Finally, planning illustrations are not a replacement for trial results. They depend on assumptions and an observed effect used as a reference; they do not show the precision actually achieved in this trial. Reporting a complete analysis, including estimates, uncertainty, populations, and missing-data methods, would be needed to support a statistical interpretation of the outcomes.

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 of the registry record is that it contains no posted analyses. The primary endpoint is identified, but no numerical outcome estimates or treatment comparisons are reported. The reason the trial was terminated is also not reported in the registry record, so the status cannot be used to infer why results are absent.

Enrollment is listed as 41, but the record does not give the number randomized to each treatment schedule or the number contributing FVC measurements at Week 6. The Safety Population is defined as randomized participants who received treatment, but its size by group is not reported. The record therefore does not permit assessment of attrition or of how many participants contributed to each endpoint.

The intervention descriptions include different active and placebo-to-active schedules, while the adverse-event summary uses a combined Placebo/Botulinum Toxin Type A label. The mapping between the schedule descriptions and the safety groups is not reported. The registry also does not state the allocation ratio, the protocol rationale for the dosing schedules, or which roles were masked.

Analysis details that would affect interpretation are not reported: the statistical model and test, any adjustment for baseline, the handling of missing data, the approach to multiple outcomes or timepoints, and any sensitivity analyses. The serious-event terms are listed with percentages without a group assignment in that listing, and death counts are not reported. These gaps limit both efficacy interpretation and comparative safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder — NCT00439140.
• Registry record last updated 2014-01-24; status last verified 2013-12.
• Results first posted 2014-01-24.
• 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

The registry record describes a randomized, parallel-group, quadruple-masked phase 3 study sponsored by Allergan, with enrollment of 41. It concerns botulinum toxin Type A for urinary incontinence associated with overactive bladder in people with spinal cord injury or multiple sclerosis. The study is listed as terminated; its start date is 2007-06 and its primary completion date is 2012-12.

The primary outcome is change from baseline in FVC, measured in liters at baseline and Week 6. Secondary outcomes include changes in urinary incontinence episodes, maximum detrusor pressure, and maximum cystometric capacity. The registry record reports zero analyses, so it does not provide numerical outcome comparisons. It does include serious and other adverse-event counts for three safety groups, but these descriptive data do not establish comparative treatment effects.