Safety and Efficacy Evaluation of Oxybutynin Topical Gel In Children With Neurogenic Bladder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Evaluation of Oxybutynin Topical Gel In Children With Neurogenic Bladder (NCT01192568), a randomized phase 4 study. The primary outcome is Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6.

2. Clinical Question

The primary outcome is a continuous measure: percentage of catheterizations without a leaking accident. Its change from baseline describes whether the recorded share of catheterizations without a leak increased or decreased over the assessment period. The registry also lists secondary measures related to urine volume and catheterization frequency.

The placebo comparison is tied to the double-blind, pre-Amendment 3 arms. The registry separately reports pre-Amendment 3 and post-Amendment 3 open-label gel arms, as well as a combined OTG summary. These groups do not all represent the same treatment contrast: the open-label arms do not have a concurrent placebo group described in their arm information.

The clinical question is therefore narrower than whether the treatment is beneficial in general. It concerns the recorded Week 6 change in a diary-based measure, within the stated pediatric population and trial structure. The registry record does not report further details of the eligibility criteria or the reason for the amendment.

3. Trial Design

The study is listed as Phase 4, randomized, quadruple-masked, and sequential. Enrollment is recorded as 52, and the status is completed. The start date is 2011-05-17 and the primary completion date is 2023-08-29. These record details describe the registry entry; they do not by themselves explain the study’s full operational history.

The brief summary describes a two-part treatment approach: children start at 0.75 g of gel per day for two weeks, then return for potential dose titration, with the dose possibly adjusted to 1 g/day, 0.5 g/day, or left at 0.75 g/day. The summary states a total treatment time of 14 weeks and a total study time of 16 weeks.

The arm descriptions provide additional detail. Before Amendment 3, the double-blind OTG and placebo arms are described as lasting 6 weeks, followed by 8 weeks of open-label OTG. The pre-Amendment 3 OTG starting dose is described as 0.75 g, with 0.5 g and 1 g sachets also listed. The post-Amendment 3 OTG arm is described as open-label treatment for 14 weeks. The registry does not report the reason for the amendment or a fuller account of how the sequential model operated.

The primary endpoint assessment is at Week 6, and the primary population is identified as ITT. The reported arm summaries include placebo, OTG before Amendment 3, OTG after Amendment 3, and combined OTG. The posted results include 16 participants for placebo, 17 for OTG before Amendment 3, 18 for OTG after Amendment 3, and 35 for combined OTG. These are outcome-specific arm figures, not a reconciliation of enrollment or of all study participation across treatment periods.

Although the registry identifies the study as quadruple-masked, the arm descriptions explicitly distinguish double-blind treatment from later open-label treatment. Further information on masking roles, randomization procedures, allocation concealment, and the original design assumptions is 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.

Before assignment: This 2-part pediatric study, was initiated as a double-blind (DB), placebo-controlled study with an open-label (OL) extension (Protocol Amendment 3). In Part 1 (Pre-Amendment 3), subjects were randomized into DB: Placebo (Pre-Amend 3) or DB: OTG (Pre-Amend 3) treatment groups for 6 weeks, then all subjects were placed into OL: OTG (Pre-Amend 3) for 8 weeks. In Part 2 (Post-Amendment 3), newly enrolled subjects were placed into OL: OTG (Post-Amend 3) for 14 weeks.

Double Blind Pre-Amendment 3

Open Label Pre-Amendment 3

Reasons for not completing this period:

Open Label Post-Amendment 3

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population

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 Percent of Catheterizations Without a Leaking Accident at Week 6, measured over Baseline (Week 0) up to Week 6.

The primary endpoint is the change from baseline to Week 6 in the percentage of catheterizations without a leaking accident. The registry describes it as the change at Week 6 of treatment or the last observation carried forward, using information recorded in a 2-day urinary diary. The measure is expressed as a percentage-point change, rather than as a count of accidents or a measure of urine volume.

In general, a change score puts the follow-up measure in relation to the participant’s baseline value. A positive group mean in this endpoint means that the average recorded percentage of catheterizations without a leak increased from baseline; a negative mean means that it decreased. This describes the direction of the recorded outcome and is not, by itself, a conclusion about treatment benefit.

The endpoint is clinically relevant to the stated study question because it focuses on catheterizations without a leaking accident, an outcome recorded in the urinary diary. Using a diary makes the outcome dependent on the completeness and accuracy of those records. The registry identifies the primary population as ITT, but it does not report further detail about diary completion, the handling of individual missing diary entries, or how the endpoint was aggregated for each participant.

For the posted Week 6 summaries, the placebo mean change was -0.45, with a standard deviation of 20.18. The OTG mean changes were 16.91 before Amendment 3, 13.82 after Amendment 3, and 15.32 for combined OTG. The combined OTG mean is a descriptive summary across the listed OTG group; the sponsor-reported comparison is a separate analysis.

7. Results Posted in the Registry

• OTG (Pre-Amend 3): mean 16.91 versus -0.45 on control; difference 17.36 (95% CI -2.68 to 37.40), standardized effect d = 0.58; z-test p = 0.090.
• OTG (Post-Amend 3): mean 13.82 versus -0.45 on control; difference 14.27 (95% CI -0.24 to 28.78), standardized effect d = 0.66; z-test p = 0.054.
• Combined OTG: mean 15.32 versus -0.45 on control; difference 15.77 (95% CI 1.75 to 29.79), standardized effect d = 0.58; z-test p = 0.027.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OTG (Pre-Amend 3): mean 14.33 versus -24.59 on control; difference 38.92 (95% CI 12.67 to 65.17), standardized effect d = 1.01; z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for OTG (Pre-Amend 3) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OTG (Pre-Amend 3): mean 14.18 versus -12.03 on control; difference 26.21 (95% CI -25.20 to 77.62), standardized effect d = 0.35; z-test p = 0.318.
  • OTG (Post-Amend 3): mean 29.78 versus -12.03 on control; difference 41.81 (95% CI -17.43 to 101.05), standardized effect d = 0.48; z-test p = 0.167.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTG (Pre-Amend 3) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTG (Post-Amend 3) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Average Number of Catheterizations Per Day at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • OTG (Pre-Amend 3): mean -0.03 versus 0.19 on control; difference -0.22 (95% CI -1.56 to 1.12), standardized effect d = -0.11; z-test p = 0.747.
  • OTG (Post-Amend 3): mean -0.67 versus 0.19 on control; difference -0.86 (95% CI -2.93 to 1.21), standardized effect d = -0.27; z-test p = 0.416.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTG (Pre-Amend 3) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTG (Post-Amend 3) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover average urine volume per catheterization, average volume per first morning catheterization, and average number of catheterizations per day. Across these measures, the posted group summaries do not form a uniformly consistent pattern. Some mean changes favor an increase in measured urine volume, while the catheterization-frequency summaries vary by OTG arm. The uncertainty is also uneven: some comparisons have broad intervals that include no difference, while the registry includes a reported analysis with an interval that does not.

These measures provide related but distinct information from the primary endpoint. Urine volume and catheterization frequency are not interchangeable with the percentage of catheterizations without a leaking accident. A direction of change on one secondary measure does not establish a corresponding change in the primary diary outcome, and it does not resolve the primary comparison’s uncertainty.

The registry reports an ANCOVA analysis for the pre-Amendment 3 urine-volume endpoint and for combined OTG on the first morning catheterization endpoint. It also reports separate analyses for pre- and post-Amendment 3 OTG on catheterizations per day, using ANCOVA and a two-sided t-test, respectively. The mix of groups and methods reinforces the need to interpret each secondary result as its own analysis rather than as a single confirmatory pattern.

In general, when multiple outcomes and comparisons are examined, nominal p-values can be less persuasive if no multiplicity strategy is specified. The registry does not report whether multiplicity was controlled or how the secondary outcomes were prioritized. These outcomes can help describe the breadth of the posted findings, but they carry less confirmatory weight than the primary endpoint and should not be used to override its sponsor-reported analysis.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6
• Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6
• Change From Baseline in Average Number of Catheterizations Per Day at Week 6

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measure, and the registry reports means and standard deviations by arm. The recalculated comparisons use posted arm-level summary statistics to estimate unadjusted mean differences. They do not reproduce the sponsor’s participant-level analysis. Because the discrepancy flag is true, the sponsor’s analysis takes precedence for interpretation of the primary comparison.

What does a mean difference represent?

In general, a mean difference is the difference between the average change in one group and the average change in the comparison group. For the primary endpoint, the units are percentage points. A positive contrast in the listed comparisons corresponds to a higher mean change in OTG than placebo. It does not mean that each participant had that change, and it does not describe the distribution of individual outcomes.

The posted standard deviations describe how spread out individual observations are around each arm mean. A larger standard deviation indicates more variability in the observed changes. In the primary endpoint, the reported standard deviations differ between arms, which is one reason that arm means alone cannot communicate how precisely a contrast is estimated.

Why are confidence intervals useful?

In general, a confidence interval communicates uncertainty around an estimate. Narrow intervals indicate greater precision under the analysis assumptions; wide intervals indicate less precision. An interval that includes zero is compatible with no mean difference as well as with effects on either side of zero within the interval. The sponsor-reported primary interval extends from -2.45 to 30.90, so it includes zero and also includes positive differences. The interval should be read alongside the analysis that produced it, not treated as a guarantee that the true effect lies within its endpoints.

How does the reported ANCOVA differ?

The registry reports an ANCOVA for the combined OTG and placebo primary comparison. ANCOVA is a regression-based method that can compare follow-up values while accounting for specified covariates, often including baseline values. The registry record does not identify the covariates, model details, or missing-data handling for this analysis. The reported estimate is a mean difference in final values. Its result is 14.22, with a 95% confidence interval from -2.45 to 30.90 and p = 0.093.

The recalculated mean differences instead use the posted group summaries and are unadjusted. Such a calculation may differ from an ANCOVA because the methods use different information and model assumptions. It should be treated as a simple comparison of posted summary statistics, not as a corrected or preferred result. The registry’s sponsor analysis remains the primary reference when it differs from the recalculation.

What does the primary population tell us?

The registry identifies the primary population as ITT, meaning the reported primary analysis is designated for the intention-to-treat population. In general, ITT analysis aims to retain participants in the groups to which they were assigned, regardless of later treatment changes. The exact operational definition, inclusion rules, and handling of post-randomization data are not reported in the registry record. The arm-level counts in the posted outcome summaries should not be taken as a complete account of participant flow.

The endpoint description says Week 6 or the last observation carried forward. In general, last observation carried forward fills a missing follow-up value with the participant’s most recently observed value. This can make assumptions about how outcomes would have changed after the last observation. The registry does not report how many observations were carried forward, why data were missing, or whether other missing-data analyses were conducted.

How should p-values be read?

In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that null model and the analysis assumptions were correct. It does not measure the size or clinical importance of a difference. Nor does a value above a conventional threshold prove that groups are identical. For the primary comparison, the sponsor-reported p-value is 0.093. The unadjusted recalculation has p = 0.027, but it is not a substitute for the sponsor’s analysis in light of the reported discrepancy.

The registry record does not report whether the primary or secondary analyses were adjusted for multiple comparisons, the prespecified testing hierarchy, or details of any interim analyses. Those omissions matter when reading several endpoints and analyses together, because repeated testing can increase the chance of finding a nominally notable result even when no true difference exists.

11. Confidence Intervals and Precision

Precision is limited by the outcome-specific group sizes and the spread of the primary outcome. The posted primary summaries include 16 participants in placebo, 17 in OTG before Amendment 3, and 18 in OTG after Amendment 3. The standard deviations range from 20.18 for placebo to 36.68 for OTG before Amendment 3. This variation means the group means should not be read as exact estimates of what would be seen in a larger population.

For the sponsor-reported combined OTG comparison, the estimated mean difference is 14.22, with a 95% confidence interval from -2.45 to 30.90. The interval spans zero and also includes positive values. Its width signals considerable uncertainty about the magnitude and even the direction of the underlying difference. The p-value of 0.093 is consistent with that imprecision; it does not establish that there is no difference.

The unadjusted recalculation yields a different estimate and interval: 15.77, with a 95% confidence interval from 1.752 to 29.79. Because the discrepancy flag is true, this recalculated interval does not displace the sponsor’s reported interval. Readers should not select the more favorable-looking result; the reported analysis takes precedence.

In general, confidence intervals are affected by both sample size and outcome variability. More information and less variability tend to improve precision, but the registry record does not report a precision target for this trial. Its original sample-size justification and design assumptions are not reported in the registry record. The posted intervals also depend on the statistical method used, so intervals from different methods are not interchangeable.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not a reconstruction of the trial’s original design. For these continuous-outcome comparisons, the figures are participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the illustrated participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect is real. The 90% power column gives the corresponding number for a 90% chance. These are planning probabilities under a model, not guarantees about a future study’s result. The figures are not observed power.

The rows describe planning for 100%, 75%, or 50% of the observed effect. A smaller assumed effect requires more participants per arm to reach the same target power. For example, the primary combined OTG comparison lists 48 participants per arm for 80% power when planning for 100% of the observed effect, compared with 85 for 75% and 190 for 50%. The corresponding 90% figures are 64, 113, and 254 participants per arm.

These illustrations rely on the observed effect from a small study, which may be an unstable basis for planning. The registry does not report the trial’s original sample-size justification, any adjustment for attrition, or other design assumptions beyond those stated for this planning illustration. The figures should therefore be read as conditional planning examples, not as evidence about the study’s actual power or its design process.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 17.360; pooled standard deviation σ = 29.857.
2. n = 2 × (1.96 + 0.842)² × 29.857² / 17.360² = 46.4, rounded up to 47 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 17.36                      # observed difference in means
sigma <- 29.8572990135929                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1192568)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 47 (80% power), 63 (90% power)
 75% of observed effect: n per arm = 83 (80% power), 111 (90% power)
 50% of observed effect: n per arm = 186 (80% power), 249 (90% power)
power.t.test: 47.4 
Simulated power at n = 47 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

For the primary comparison of combined OTG with placebo, the registry reports an ANCOVA mean difference in final values of 14.22, with a 95% confidence interval from -2.45 to 30.90 and p = 0.093. The sponsor-reported analysis is the analysis to prioritize for this comparison.

The simple recalculation from posted arm summaries gives a mean difference of 15.77, with a 95% confidence interval from 1.752 to 29.79 and p = 0.027. This is an unadjusted calculation, not a reproduction of the ANCOVA. Its estimate and interval differ from the sponsor’s result. Because the discrepancy flag is true, the sponsor’s own analysis takes precedence; the recalculation should be viewed as a secondary descriptive check, not as a competing final conclusion.

In general, an adjusted model and an unadjusted comparison can differ because they may use different outcome formulations, covariates, and assumptions. The registry record does not report enough model detail to identify the reason for this specific discrepancy. It does not report the ANCOVA covariates or the full analysis specification. No explanation should be inferred from the difference alone.

The distinction is important: the sponsor’s interval includes zero, while the unadjusted recalculation’s interval does not. Reporting only the recalculation would overstate the strength of evidence relative to the sponsor-reported primary analysis. The sponsor’s estimate also remains imprecise, and its interval permits a range of possible effects.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and lists secondary outcomes, but it does not report a multiplicity adjustment, a gatekeeping strategy, or a hierarchy for testing the outcomes. It also does not report whether interim analyses were planned or conducted. Without those details, the nominal p-values across multiple outcomes and comparisons should not be treated as though they each came from a single isolated test.

In general, testing multiple hypotheses increases the chance that at least one result appears notable by chance. Multiplicity procedures manage that issue by adjusting how evidence is evaluated across tests. The appropriate interpretation depends on the prespecified analysis plan, which is not reported in the registry record. This uncertainty is especially relevant to secondary endpoints, where analyses include different OTG groupings and more than one statistical method.

The primary endpoint description refers to Week 6 or the last observation carried forward. The registry does not report the amount or pattern of missing primary data, reasons for missingness, the number of values carried forward, or sensitivity analyses. In general, carrying the last observed value forward assumes that this value is a reasonable substitute for the unobserved follow-up outcome; that assumption may not hold in every setting. No conclusion about the actual impact of missing data can be drawn from the available description.

The primary population is named as ITT, but the registry record does not report a detailed analysis-population definition, participant disposition, or the reasons that outcome-level counts differ across listed arms and analyses. It also does not explain whether the combined OTG group was prespecified or how it was formed. The outcome counts should therefore be read as analysis-specific summaries rather than as a complete account of who entered, completed, or contributed data at each stage.

Further details of randomization, masking roles, protocol amendments, analysis covariates, and original sample-size justification are not reported in the registry record. These omissions constrain assessment of analysis choices and prevent a complete reconstruction of the planned statistical framework.

16. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: device malfunction (10.5%), urosepsis (5.3%), limb deformity (5.3%), inguinal hernia (3.0%), pyelonephritis (3.0%).

The registry reports serious adverse events by treatment period and arm. There were 0 serious adverse events among 16 participants at risk in the double-blind placebo group and 0 among 17 at risk in the double-blind OTG pre-Amendment 3 group. In the open-label OTG pre-Amendment 3 group, 3 serious adverse events were reported among 33 at risk; in the open-label post-Amendment 3 OTG group, 3 were reported among 19 at risk. No deaths were reported in any of these groups.

The registry lists device malfunction at 10.5%, urosepsis and limb deformity at 5.3% each, and inguinal hernia, pyelonephritis, and urinary tract infection at 3.0% each among the top serious-event terms. These terms describe events recorded in the registry; they do not establish that treatment caused them.

In general, safety counts require context about the period at risk, how events were collected, and whether participants contributed to more than one treatment-period group. The registry’s arm descriptions include transitions from double-blind to open-label treatment, so these group counts should not be treated as simple independent comparisons of risk. The registry does not report further detail on event adjudication, exposure-adjusted rates, or causal attribution. Counts alone cannot determine comparative safety.

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

The primary summaries describe a higher mean Week 6 change in the percentage of catheterizations without a leaking accident in the OTG groups than in placebo. The sponsor-reported ANCOVA comparison for combined OTG and placebo is 14.22, with a 95% confidence interval from -2.45 to 30.90 and p = 0.093. The interval includes zero and spans a broad range of possible differences, so the result is uncertain in magnitude and does not provide strong statistical evidence against no difference under conventional interpretation.

This does not prove that the groups are identical, nor does it establish that the treatment has no effect. It also does not establish that OTG improves the outcome. The result is one estimate from a registry-reported analysis, with limited precision and details of the analysis plan not reported in the registry record. The unadjusted recalculation differs and is not the result to prioritize because the discrepancy flag is true.

The endpoint is a diary-based measure of catheterizations without a leaking accident at Week 6. It does not represent every aspect of bladder function, safety, quality of life, or longer-term outcomes. The registry lists secondary measures of urine volume and catheterization frequency, but they address different outcomes and do not substitute for the primary endpoint.

Results from the open-label OTG groups should be interpreted separately from the placebo comparison. Open-label treatment does not provide the same concurrent placebo contrast described for the double-blind pre-Amendment 3 arms. The combined OTG summary is not itself evidence that all treatment periods or amendment groups had the same experience.

The registry reports serious adverse events in open-label groups and none in the listed double-blind groups, with no deaths reported. Those counts do not establish cause or comparative risk. Overall, the record describes observed measurements and uncertainty; it does not support broad conclusions beyond the specific groups, endpoint, and assessment period.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty should be read together. The combined OTG arm mean and the sponsor-reported contrast may look directionally positive, but the sponsor’s confidence interval extends from a small negative value to a sizeable positive value. That range conveys more than the estimate alone: it shows that the data do not pin down the size of the difference precisely.

It also illustrates why the named primary analysis matters. An unadjusted re-calculation from arm summaries gives a different inferential result from the sponsor-reported ANCOVA. Because the discrepancy flag is true, the sponsor’s analysis takes precedence. A re-calculation can be informative as a check on posted summaries, but it is not interchangeable with an analysis using the trial’s participant-level data and model.

The amendment and treatment-period structure adds another statistical consideration. The registry distinguishes double-blind placebo and OTG treatment from open-label OTG periods, and it reports separate amendment groups as well as a combined OTG summary. The resulting comparisons are not all equivalent. Clear separation of randomized comparisons from open-label descriptions is important when interpreting the estimates.

Finally, the record shows why multiplicity and missing-data information are essential to a complete reading. Several outcomes and analyses are listed, but the registry does not report a multiplicity strategy or detailed missing-data handling beyond the endpoint’s last-observation-carried-forward description. Those details affect how confidently individual results can be treated as confirmatory. The statistical value of the record lies in examining estimates, intervals, analysis distinctions, and limitations together, rather than relying on a single p-value.

19. 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 outcome-specific groups are small, and the primary endpoint has substantial spread within arms. This limits precision, as reflected in the broad sponsor-reported confidence interval. The registry record does not report the original sample-size justification, so the basis for the enrolled sample cannot be assessed from this entry.

The study structure changed across amendment groups. The pre-Amendment 3 arms include a double-blind period followed by open-label treatment, whereas the post-Amendment 3 OTG arm is described as open-label. The registry does not explain the amendment or report enough detail to determine how the amendment affected the planned comparisons. Combining OTG groups may obscure differences between those treatment periods.

The primary endpoint relies on a 2-day urinary diary, and its description permits last observation carried forward. The registry does not report diary completeness, missing-data amounts, reasons for missing observations, or sensitivity analyses. Consequently, the effects of missingness and the carry-forward approach cannot be assessed.

The sponsor-reported ANCOVA details are incomplete in the registry record: covariates and model specifications are not reported. The difference between that analysis and the unadjusted recalculation is flagged, but no explanation is reported. Multiplicity procedures, interim analyses, detailed participant flow, randomization methods, and masking roles are also not reported.

The safety summaries are organized by treatment-period groups, including open-label periods. The record does not provide the additional exposure and event-attribution detail needed to interpret the counts as comparative risks. These limitations do not invalidate the posted results, but they narrow the conclusions that can be drawn from them.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Evaluation of Oxybutynin Topical Gel In Children With Neurogenic Bladder — NCT01192568.
• Registry record last updated 2024-09-04; status last verified 2024-08.
• Results first posted 2024-09-04.
• 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.

23. Record Summary

NCT01192568 is a completed Phase 4 randomized study of oxybutynin chloride 10% topical gel in children with overactive bladder associated with a neurogenic condition. The registry describes a sequential, quadruple-masked study and includes double-blind and open-label treatment periods around Amendment 3.

The primary endpoint is change from baseline to Week 6 in the percentage of catheterizations without a leaking accident, recorded in a 2-day urinary diary. The sponsor-reported combined OTG comparison gives a mean difference of 14.22, a 95% confidence interval from -2.45 to 30.90, and p = 0.093. Because the registry flags a discrepancy with the unadjusted recalculation, the sponsor analysis takes precedence.

Secondary results address urine volume and catheterization frequency. Serious adverse events are reported in the open-label groups, none in the listed double-blind groups, and no deaths are reported. Important details—including multiplicity handling, fuller missing-data information, and the original design assumptions—are not reported in the registry record.