Clinical Trial Comparing Two Bladder Instillations for IC/BPS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial Comparing Two Bladder Instillations for IC/BPS (NCT03463915), a randomized phase 3 study. The primary outcome is Change From Baseline in Treatment Response as Measured by the Total Score on the O'Leary-Sant Questionnaire.

2. Clinical Question

The registry describes a comparison of two bladder-instillation regimens for women with interstitial cystitis/bladder pain syndrome (IC/BPS). Both regimens used the standard cocktail; triamcinolone acetonide was included in one and omitted from the other. The central statistical question is whether the mean change in O’Leary-Sant total score from baseline to week 6 differed between the groups.

3. Trial Design

The registry classifies this as a phase 3, randomized, double-masked, parallel-group trial. The study is marked completed. Its recorded start date is 2019-01-25, and its primary completion date is 2020-10-23. Planned enrollment was 90.

Participants were assigned to bladder instillations with or without triamcinolone acetonide. Both arms were described as receiving six weekly instillations of the standard cocktail. The registry does not explain the allocation procedure beyond identifying the study as randomized, and details of how masking was maintained are not reported in the registry record.

The primary measure was change from baseline to week 6 in the O’Leary-Sant total score. The outcome description says assessments were made at baseline, 3 and 6 weeks, with the change to week 6 reported. The primary outcome summaries list a mean change and standard deviation for each group. The registry also names patient-reported questionnaires and adverse events as secondary outcomes. The posted secondary results include change scores for the PUF Questionnaire, OAB-q, and PFDI; other named secondary outcomes do not have numerical summaries in the record described.

The trial design information does not state the original sample-size rationale, the intended primary analysis model, or the analysis population. Those details are not reported in the registry record. The outcome summaries alone do not establish how participants were handled if they did not complete treatment or an assessment.

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

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 Treatment Response as Measured by the Total Score on the O'Leary-Sant Questionnaire, measured over Assessed at baseline, 3 and 6 weeks; change from baseline to week 6 reported.

The primary endpoint is the change from baseline to week 6 in the total score on the O’Leary-Sant Questionnaire. The registry describes a score range of 0–36, with 0 representing no symptoms and 36 representing the most severe symptoms. A change score expresses how much the measured symptom score shifted over the assessment period. A negative change indicates a decrease in the score relative to baseline; the score description therefore gives context for the direction of the reported means.

This endpoint is used to compare average symptom-score changes between the randomized groups. A between-group comparison is more informative for the treatment question than considering either group’s change in isolation, since change over time within a group does not by itself show whether the regimens differed. The result remains a questionnaire-based measure, not a direct measure of every aspect of IC/BPS or of an individual participant’s experience.

The record reports group means and standard deviations for the change score, but does not report a clinically important difference threshold or explain how such a threshold was selected. Thus, the numerical comparison describes the size and uncertainty of the average difference, but does not by itself establish whether a difference would be meaningful to patients.

7. Results Posted in the Registry

• Bladder Instillation WITHOUT Triamcinolone Acetonide: mean -5.80 versus -6.70 on control; difference 0.90 (95% CI -2.23 to 4.03), standardized effect d = 0.12; z-test p = 0.572.

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.

Pelvic Pain and Urgency/Frequency (PUF) Questionnaire

• 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:
  • Bladder Instillation WITHOUT Triamcinolone Acetonide: mean -2.70 versus -5.30 on control; difference 2.60 (95% CI 0.10 to 5.10), standardized effect d = 0.49; z-test p = 0.042.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Bladder Instillation WITHOUT Triamcinolone Acetonide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Overactive Bladder Questionnaire (OAB-q)

• 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:
  • Bladder Instillation WITHOUT Triamcinolone Acetonide: mean -18.80 versus -24.20 on control; difference 5.40 (95% CI -5.07 to 15.87), standardized effect d = 0.25; z-test p = 0.312.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Bladder Instillation WITHOUT Triamcinolone Acetonide and the control. The interval gives the range of effects that remain compatible with the data.

Pelvic Floor Distress Inventory (PFDI)

• 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:
  • Bladder Instillation WITHOUT Triamcinolone Acetonide: mean -6.40 versus -5.30 on control; difference -1.10 (95% CI -6.04 to 3.84), standardized effect d = -0.11; z-test p = 0.663.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Bladder Instillation WITHOUT Triamcinolone Acetonide and the control. The interval gives the range of effects that remain compatible with the data.

The registry names several secondary domains, including pelvic pain and urgency/frequency, overactive bladder symptoms, pelvic floor distress, sexual function, pain response, and adverse events. Numerical change-score summaries are posted for the PUF Questionnaire, OAB-q, and PFDI. The other named secondary measures are not accompanied by numerical summaries in the record described. This leaves the secondary evidence incomplete across the full set of outcomes named in the registry.

Across the posted continuous secondary results, the comparison estimates and their precision do not form a uniform pattern. One unadjusted secondary comparison has a confidence interval that excludes zero and an unadjusted p-value of 0.042, while the intervals for other posted secondary comparisons include zero. The secondary results therefore do not all point to the same level of certainty. They concern different instruments and symptom constructs, so they should not be treated as repeated measurements of one identical outcome.

The primary O’Leary-Sant comparison does not clearly distinguish the groups. The secondary findings may provide context about other measured domains, but they do not replace the primary result. Nor does an apparent difference on a secondary questionnaire establish a corresponding difference in the primary endpoint or in overall treatment response.

Unadjusted secondary results carry less weight because the registry does not report a multiplicity strategy or identify which secondary comparisons, if any, were intended as confirmatory. When many outcomes are tested, the chance of observing at least one nominally unusual result can increase. This is a general statistical concern; the record does not report how the trial’s investigators addressed it. The secondary p-values should consequently be viewed as exploratory signals rather than conclusive evidence, particularly without a prespecified hierarchy, adjustment method, or full analysis record.

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

• Pelvic Pain and Urgency/Frequency (PUF) Questionnaire
• Overactive Bladder Questionnaire (OAB-q)
• Pelvic Floor Distress Inventory (PFDI)
• Sexual Function Measured by the Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) Questionnaire
• Change From Baseline in Treatment Response as Measured by the Visual Analogue Scale (VAS) for Pain
• Number of Participants With at Least One Adverse Event

9. Statistical Interpretation

10. Statistical Methods Explained

The posted continuous outcomes are summarized by a mean change and standard deviation for each group. A mean is the arithmetic average of the observed change scores among the participants included in that outcome summary. The standard deviation describes how spread out those scores are around the mean. It reflects variation among observed participants; it is not itself a confidence interval for the mean or for the treatment contrast.

What does the between-group mean difference represent?

The primary comparison is expressed as the mean change in the group without triamcinolone acetonide minus the mean change in the group with triamcinolone acetonide. The reported estimate is 0.9. With this ordering, a positive estimate means the average change in the comparator group is numerically higher, or closer to zero, than the average change in the triamcinolone group. The sign depends on the stated order of subtraction, so it is important to read the group order as well as the value.

The comparison is unadjusted: it uses the posted group summaries rather than accounting for other variables in a reported model. The record does not report an adjusted primary analysis or its specification. An unadjusted comparison is a straightforward description of the observed group difference, but it does not answer whether an adjusted analysis would yield the same estimate.

How should the confidence interval and p-value be read?

A confidence interval gives a range of values compatible with the observed estimate under the method used to construct it. For the primary mean difference, the interval is -2.225 to 4.025. It crosses zero, the value corresponding to no difference in mean change. The interval therefore indicates uncertainty in both the direction and size of the group difference. It does not mean that every value in the interval is equally plausible, and it does not provide a probability that a particular treatment effect is true.

The unadjusted p-value is 0.572. A p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a complete analysis plan, so the result should be understood as the unadjusted comparison recorded with the summary statistics.

Why do spread and sample size affect precision?

In general, estimates tend to be less precise when outcome values vary substantially or when fewer observations contribute to an estimate. The standard deviations in the primary group summaries describe the observed spread, while the interval for the mean difference reflects uncertainty in the contrast. These concepts are related but not interchangeable. A standard deviation describes participant-level variation; a confidence interval describes uncertainty about an estimated quantity.

The primary summaries list 45 participants in each arm. The participant counts for secondary outcomes differ, so their estimates need to be read in light of their own contributing group sizes rather than assuming the same analysis set for every measure. The reason for those differences is not reported in the registry record. They could reflect availability of outcome measurements or other analysis decisions, but the registry does not state the explanation.

The standardized effect size listed for the primary comparison is 0.119. A standardized effect expresses a mean difference relative to a measure of outcome variability, making it less tied to the original score units. It does not replace the original-scale estimate or the confidence interval. In this trial, the original score units and the interval remain important for understanding the actual reported contrast. The record does not provide a threshold for interpreting the standardized value as clinically important.

What is and is not established by the reported analyses?

The registry lists no reported analysis records. The numerical comparisons accompanying the posted summaries are unadjusted and do not document a model for repeated assessments, covariate adjustment, or handling of missing outcomes. Although measurements were assessed at baseline, 3 and 6 weeks, the primary result reported is change from baseline to week 6; the registry summary does not describe a longitudinal analysis using all assessment times.

The comparison also does not establish that the study was designed to test equivalence or noninferiority. A confidence interval that includes zero is not an equivalence finding. To make an equivalence claim, an analysis would need a prespecified margin and a suitable design and interpretation; those details are not reported in the registry record. The summary supports a description of the estimated difference and its precision, but not a stronger claim about equality of the regimens.

11. Confidence Intervals and Precision

The primary mean difference is 0.9, with a confidence interval from -2.225 to 4.025. Because the interval includes zero, the posted primary comparison is compatible with no difference in mean change. It also includes negative values and positive values, corresponding to possible differences in either direction under the reported contrast ordering. The range is broad enough that the point estimate alone should not be read as a precise estimate of the treatment contrast.

For context, the group means were -6.7 with triamcinolone and -5.8 without it, and the corresponding standard deviations were 7.1 and 8.0. The means describe average observed changes; the standard deviations describe variability across participants. The confidence interval addresses uncertainty in the difference between the means. These summaries answer different questions and should not be substituted for one another.

The record does not report a threshold for a clinically important difference on the O’Leary-Sant score. Consequently, it is not possible from these summaries alone to determine whether all or part of the interval represents differences that would matter to patients. The interval’s inclusion of zero is also not proof that the treatments have the same effect. It indicates that the observed data do not precisely rule out no difference, while leaving uncertainty about the size and direction of any underlying difference.

Confidence intervals depend on the analysis method and assumptions. The registry does not provide a full statistical analysis plan or enough detail to assess every assumption underlying the comparison. The interval is therefore best read as the uncertainty summary accompanying the posted unadjusted comparison, not as a complete account of uncertainty from every possible source.

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 for these continuous outcomes are participants per arm, rather than a total number of events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record; these figures are planning illustrations based on the observed comparison, not a description of the trial’s design process.

The 80% power column gives the participants per arm estimated to provide an 80% chance of detecting the chosen effect under the stated assumptions if that effect is real and the assumptions hold. The 90% power column uses a higher target chance of detection. Higher target power generally requires more participants for the same effect and assumptions. These are prospective planning quantities, not a measure of how likely the completed trial was to detect an effect after its results were observed. This is not observed power.

The rows that plan for 100%, 75%, and 50% of the observed effect use progressively smaller target differences. Smaller effects are harder to distinguish from random variation and therefore require more participants. The figures should be interpreted as illustrations tied to the observed effect and the stated calculation assumptions, not as recommendations or as a reconstruction of the trial’s original enrollment decision.

The sample-size curve expresses the same planning relationship across effect assumptions: a smaller effect corresponds to a larger required sample under otherwise unchanged assumptions. Neither the curve nor the listed planning figures resolves the uncertainty in the trial’s observed estimate, and they do not account for unreported features of the original design or analysis.

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 = 0.900; pooled standard deviation σ = 7.563.
2. n = 2 × (1.96 + 0.842)² × 7.563² / 0.900² = 1,108.6, rounded up to 1,109 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 <- 0.9                      # observed difference in means
sigma <- 7.56339870693064                     # 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(3463915)
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 = 1,109 (80% power), 1,485 (90% power)
 75% of observed effect: n per arm = 1,971 (80% power), 2,639 (90% power)
 50% of observed effect: n per arm = 4,435 (80% power), 5,937 (90% power)
power.t.test: 1109.6 
Simulated power at n = 1,109 per arm: 0.797 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, but does not report how the analyses were organized or whether any adjustment was made for testing multiple outcomes. It also lists no reported analysis records. The primary endpoint is identified, but the statistical plan for the primary and secondary comparisons, including any hierarchy or decision rules, is not reported in the registry record.

Multiplicity matters because each additional statistical test creates another opportunity for a result to appear unusual by chance, even when no underlying difference exists. A nominal p-value for an individual secondary comparison does not by itself account for the full set of outcomes examined. Without a reported adjustment or a prespecified strategy, secondary findings should be interpreted cautiously and are not equivalent to a single confirmatory test.

The outcome summaries also do not describe missing-data handling. Counts contributing to the primary and secondary outcomes differ across measures. The record does not explain why participants are absent from particular outcome summaries, whether values were imputed, or whether analyses used all randomized participants. The analysis population and any exclusions are not reported in the registry record. This prevents a full assessment of whether the reported estimates could be affected by missingness or selection into the available outcome data.

The registry describes assessments at baseline, 3 and 6 weeks, but reports the primary change from baseline to week 6. It does not state whether intermediate measurements were included in a repeated-measures model, how deviations from the planned assessment schedule were treated, or whether sensitivity analyses were conducted. Such details are not reported in the registry record and should not be inferred from the available summaries.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event summaries list 45 participants at risk in each group, with 0 serious adverse events attributed in each group. Deaths are listed as 0 in both groups. These figures describe the recorded serious events in the registry; they do not establish that no other harms occurred or that the regimens have identical safety profiles.

The record separately lists other adverse events for 5 participants in the group receiving triamcinolone and 1 participant in the group without it, with 45 at risk in each group. Those figures are not serious adverse events and should not be combined with the serious-event counts. The registry’s summary does not provide event descriptions in the listed serious-event terms, and it does not give enough detail to assess event severity, timing, or causal attribution beyond the reported categories.

Safety summaries are descriptive. The absence of recorded serious events in these group summaries does not prove that the risk is zero, particularly when the registry does not provide further detail about follow-up duration, event ascertainment, or analysis procedures. The figures should be read as reported counts, not as a comprehensive safety conclusion.

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

The primary result describes average change in O’Leary-Sant symptom scores from baseline to week 6 for participants represented in the posted summaries. The mean changes were negative in both groups, and the estimated between-group difference was small relative to the uncertainty represented by its confidence interval. The unadjusted comparison did not clearly distinguish the groups on this endpoint.

This result does not establish that the two regimens are equivalent, that they have identical effects, or that either regimen is effective or ineffective. The registry does not report an equivalence margin or a noninferiority framework. A non-significant or uncertain comparison is not a test of sameness. The interval allows for a range of possible differences, including values in either direction, and no clinically important difference threshold is reported.

The trial compared two active instillation regimens that shared the described standard cocktail; the contrast concerned inclusion or omission of triamcinolone acetonide. It does not compare bladder instillation with no instillation, and the findings cannot answer questions beyond this particular contrast and measured outcomes. The registry describes the study population as women with IC/BPS, so the results should not automatically be generalized to populations or treatment settings not described by the record.

The secondary outcomes provide additional but incomplete context. They cover other symptom domains, and their unadjusted results are less conclusive when the multiplicity approach and analysis plan are not reported. The safety counts likewise describe recorded events but do not prove an absence of risk. Overall interpretation should remain tied to the posted estimates, their precision, and the information the registry record actually reports.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an observed change within each group and a comparative treatment estimate. Both groups had negative mean changes on the primary score, but the study question concerns whether those changes differed between randomized groups. The mean difference and its confidence interval address that comparative question more directly than either group’s mean viewed alone.

The confidence interval is important because the primary point estimate is not an exact description of the underlying difference. Its range includes zero and values on both sides, making clear that the data leave uncertainty about the direction and size of the contrast. The unadjusted p-value should not be interpreted as proof of no effect, just as an isolated secondary result should not be treated as definitive without a reported multiplicity strategy.

The record also makes visible a common distinction between trial enrollment and outcome-specific analysis counts. The primary summaries list 45 participants in each arm, while counts differ among secondary outcome summaries. Without an explanation of missing data or analysis populations, readers cannot determine from the posted summaries why those denominators vary. This is a limitation in interpreting precision and potential selection effects.

Finally, the registry’s planning illustrations show how required enrollment depends on the effect size a future study aims to detect. They use the observed effect as a planning reference, rather than reporting the original study’s sample-size rationale. Separating those planning calculations from the trial’s actual design assumptions helps avoid treating post-result calculations as evidence about the trial’s original power or intent.

18. 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 available registry information does not report the original sample-size calculation or justification, so it is not possible to assess whether the planned enrollment was chosen to detect a particular clinically important difference. The planning illustrations based on the observed effect are separate from that original design question.

The record provides group means, standard deviations, and unadjusted comparisons, but no reported analysis records. It does not describe covariate adjustment, the analysis population, treatment of protocol deviations, or missing-data methods. Outcome-specific participant counts vary, and the reasons for those differences are not reported in the registry record.

The primary endpoint is reported as a baseline-to-week-6 change, although assessments were scheduled at baseline, 3 and 6 weeks. The registry summary does not explain whether the intermediate measurements contributed to any analysis or how repeated measurements were handled. A clinically important difference threshold for the O’Leary-Sant score is also not reported, limiting interpretation of the size of the estimate.

The registry does not report a multiplicity plan for the secondary outcomes. Several domains are named, but numerical summaries are not available for every named measure. Thus, the secondary findings are incomplete and should not be considered a comprehensive evaluation of all listed outcomes. The safety record gives summary counts without detailed descriptions, timing, or follow-up information sufficient for a broad safety assessment.

Finally, the registry’s description of the intended population is women with IC/BPS and the comparison is between two instillation regimens sharing the standard cocktail. The record does not establish how well the results apply to other populations, regimens, or comparisons. These limitations do not negate the posted summaries, but they constrain the conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Clinical Trial Comparing Two Bladder Instillations for IC/BPS — NCT03463915.
• Registry record last updated 2021-09-01; status last verified 2021-08.
• Results first posted 2021-09-01.
• 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.

22. Record Summary

The registry describes a completed, randomized, double-masked, parallel-group phase 3 trial comparing six weekly bladder instillations with and without triamcinolone acetonide in women with IC/BPS. Planned enrollment was 90. The primary endpoint was change from baseline to week 6 in O’Leary-Sant total score.

The posted primary mean changes were -6.7 with triamcinolone and -5.8 without it. The mean difference was 0.9, with a confidence interval from -2.225 to 4.025 and an unadjusted p-value of 0.572. The estimate does not clearly distinguish the groups, and the interval leaves uncertainty about the direction and size of the difference.

Secondary outcomes and adverse-event counts provide additional but incomplete information. The registry does not report the original sample-size rationale, multiplicity strategy, missing-data methods, or analysis populations.