A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function (NCT00478881), a randomized phase 2 study. The primary outcome is Change From Baseline in Bladder Volume at First Detrusor Contraction at 6 Weeks.

2. Clinical Question

The endpoint is a urodynamic measure: bladder volume, in mL, at the point of the first detrusor contraction. The comparison concerns the average change recorded for each group, not an individual participant’s response. The registry reports least-squares means and a sponsor ANCOVA comparison for the primary outcome. A separate simple re-calculation from the posted group summaries provides an unadjusted comparison for statistical context.

The registry record describes a randomized, double-blind, placebo-controlled study and identifies the trial as Phase 2. It reports enrollment of 397 participants. The primary analysis population was narrower than the enrollment count because it required particular safety, randomization, and urodynamic measurement criteria. Reasons why participants did or did not meet those criteria are not reported in the registry record.

3. Trial Design

This was a randomized, parallel-group, placebo-controlled study with triple masking, according to the registry. The two groups received either vardenafil hydrochloride 10 mg twice daily or matching placebo twice daily, both for 6 weeks. The registered condition terms are overactive bladder and detrusor overactivity. The record lists the phase as Phase 2 and enrollment as 397.

The registry describes a screening and run-in assessment, a randomization visit with urodynamic measurements, a safety visit during treatment, and a final visit that included repeat urodynamic assessments. It also describes a telephone call after the final visit to assess serious adverse events. These procedures provide context for how outcomes and safety were assessed; they do not by themselves establish how missing measurements were handled beyond the stated LOCF approach for the primary endpoint.

The primary endpoint used measurements from baseline and up to 6 weeks of treatment. The record says missing data were imputed using last observation carried forward. The primary analysis population was described as a modified intention-to-treat population: participants had to be in the safety sample, be randomized correctly according to the Urodynamic Adjudication Board, and have valid baseline and on-treatment urodynamic measurements. The registry’s description ends with a qualification that the population number is not identical to another number, but does not complete the explanation. Further details about the relevant count are not reported in the registry record.

The registry identifies Bayer as sponsor and lists the study status as completed. It gives the start as 2007-08 and primary completion as 2008-11. The original sample-size justification and the trial’s prespecified statistical plan are not reported in the registry record. The planning illustrations associated with the posted results are not a substitute for those original design details.

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: Number of participants screened: 635. Number of participants enrolled and randomized (started Overall study): 397. Number of participants who had taken at least one dose (Safety population): 396.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified intention-to-treat (mITT): participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the 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 Bladder Volume at First Detrusor Contraction at 6 Weeks, measured over baseline and up to 6 weeks of treatment Last Observation Carried Forward (LOCF).

The primary endpoint is change from baseline in bladder volume at first detrusor contraction at 6 weeks, measured in mL. It is based on urodynamic assessment by cystometry. The outcome captures the volume at a specified event during bladder filling, making it a continuous physiological measure rather than a count of symptoms or events.

The registry reports least-squares means for the groups and describes the primary comparison using ANCOVA on final values. It specifies measurements from baseline and up to 6 weeks, with missing data imputed by last observation carried forward. The primary analysis population required valid baseline and on-treatment urodynamic measurements, in addition to the stated safety-sample and randomization criteria.

As a general statistical point, a continuous endpoint retains information about the magnitude of measurements rather than reducing them to categories. Comparing average changes can therefore describe the direction and scale of group-level differences. It does not show that every participant changed by the group average, nor does it establish how a measured difference relates to symptoms or other outcomes. The registry record does not report a threshold for a clinically important change in this measure, so statistical estimates alone cannot establish whether a difference would be important to participants.

7. Results Posted in the Registry

• Vardenafil HCl (Levitra, BAY38-9456): mean 44.99 versus 36.95 on control; difference 8.05 (95% CI -16.99 to 33.08), standardized effect d = 0.08; z-test p = 0.529.

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 H2O Detrusor Pressure at First Contraction at 6 Weeks

• 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:
  • Vardenafil HCl (Levitra, BAY38-9456): mean 0.09 versus 0.74 on control; difference -0.66 (95% CI -7.59 to 6.28), standardized effect d = -0.02; z-test p = 0.852.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vardenafil HCl (Levitra, BAY38-9456) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Volume at First Detectable Leakage at 6 Weeks

• 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:
  • Vardenafil HCl (Levitra, BAY38-9456): mean 42.31 versus 26.72 on control; difference 15.59 (95% CI -5.77 to 36.95), standardized effect d = 0.18; z-test p = 0.153.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vardenafil HCl (Levitra, BAY38-9456) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Maximum Cystometric Bladder Capacity at 6 Weeks

• 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:
  • Vardenafil HCl (Levitra, BAY38-9456): mean 40.27 versus 27.90 on control; difference 12.37 (95% CI -7.98 to 32.73), standardized effect d = 0.15; z-test p = 0.233.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vardenafil HCl (Levitra, BAY38-9456) and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary measures covering urodynamic pressure and volumes, urgency and involuntary urine discharge, urinary flow in a specified subgroup, and an overactive bladder questionnaire score. The quantified secondary results include detrusor pressure at first contraction, volume at first detectable leakage, and maximum cystometric bladder capacity. For these outcomes, the reported group estimates differ in direction and magnitude, and the confidence intervals for the simple comparisons include zero.

This broad pattern does not provide a consistent, precise signal across the quantified secondary measures. It also does not replace the primary endpoint result: secondary outcomes address related but distinct aspects of bladder function and symptoms. The individual estimates and their uncertainty should be read in their own measurement units and populations, rather than combined informally into a single conclusion. Detailed estimates for the other listed secondary outcomes are not reported in the registry record.

Unadjusted secondary comparisons carry less weight when many outcomes are examined because the chance of observing an apparently notable result by chance can increase as the number of comparisons grows. General statistical explanation: multiplicity can be addressed through prespecified testing sequences, adjustment procedures, or an explicitly exploratory interpretation. The registry record does not report whether a multiplicity adjustment or hierarchical testing plan was used. Without that information, secondary p-values should not be treated as stand-alone confirmatory evidence.

The secondary outcomes can therefore be viewed as contextual evidence about related measures, not independent confirmation of the primary result. Their interpretation is further limited by the absence of reported estimates for all listed outcomes and by the lack of registry detail about the planned multiplicity strategy.

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

• Change From Baseline in H2O Detrusor Pressure at First Contraction at 6 Weeks
• Change From Baseline in Volume at First Detectable Leakage at 6 Weeks
• Change From Baseline in Maximum Cystometric Bladder Capacity at 6 Weeks
• Change From Baseline in Volume at First Desire to Void at 6 Weeks
• Change From Baseline in Average Number of Urgencies Per Day at 6 Weeks
• Change From Baseline in Average Number of Daily Involuntary Discharges of Urine at 6 Weeks
• Change From Baseline in Peak Urinary Flow at 6 Weeks in Men Aged 50 Years and Older
• Change From Baseline in the Total Score of the Overactive Bladder Questionnaire (OAB-q) at 6 Weeks

9. Statistical Interpretation

10. Statistical Methods Explained

The registry’s primary analysis is described as ANCOVA, with the reported parameter labeled mean difference in final values. The endpoint itself is a change from baseline, and the registry specifies least-squares means for the group summaries. ANCOVA is a regression-based method that can compare groups while accounting for covariates included in the model. The specific covariates and full model specification are not reported in the registry record.

What does a group mean describe?

For a continuous outcome, a mean describes the average measurement or average change within a group. The posted primary summaries are 44.99 mL for vardenafil and 36.95 mL for placebo. A group mean does not describe the spread of individual participant responses, and it does not imply that each participant changed by that amount. The registry identifies the summaries as least-squares means, which are model-based estimates rather than necessarily raw arithmetic averages.

The reported dispersion for these summaries is the standard error. A standard error describes the uncertainty in an estimated mean, rather than the variability among individual participants. It is therefore not interchangeable with a standard deviation. The re-calculation uses the posted summary statistics and is explicitly an approximate, unadjusted comparison; it is not the same analysis as the sponsor’s ANCOVA.

How should the mean difference be read?

A mean difference expresses the contrast between two group estimates on the original measurement scale. In the unadjusted re-calculation, the direction is vardenafil minus placebo, giving 8.045 mL. The sponsor’s reported ANCOVA contrast is placebo minus vardenafil, giving -8.045 mL. Reversing the order of the groups reverses the sign while retaining the same magnitude. The registry’s reported estimate is the sponsor’s model-based result, while the re-calculation offers a simple comparison derived from the posted group summaries.

What does a confidence interval convey?

A confidence interval gives a range of values compatible with the data under the analysis and its assumptions. The primary re-calculated 95% interval runs from -16.99 to 33.08 mL for vardenafil minus placebo. Because it includes zero, the data are compatible with no group difference as well as with differences in either direction. The interval also indicates that the estimate is not precise enough to isolate a narrow range of plausible effects. General statistical interpretation: a confidence interval is not a guarantee that the true value lies within the particular reported interval, and its meaning depends on the model and data assumptions.

The unadjusted p-value of 0.529 summarizes how unusual data at least as incompatible with a null difference would be under that null and the calculation’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The sponsor reports a p-value of 0.529 for ANCOVA. The values are close, but the analyses are not identical: one is a sponsor model-based analysis and the other is a simple unadjusted re-calculation.

Why can over-dispersion matter?

General statistical explanation: if participant measurements vary substantially around their group averages, the uncertainty in a group comparison can be large, making the estimate less precise. In count outcomes, over-dispersion means variability exceeds what a simple model assumes; for a continuous outcome such as this one, the broader lesson is that the outcome’s variability and the model’s assumptions affect standard errors and intervals. The registry’s primary endpoint is continuous, and its reported summary dispersion is standard error. The record does not report a specific over-dispersion assessment or a model diagnostic for this endpoint.

The re-calculation’s planning illustrations use a normal approximation and an effect based on the observed estimate. Such calculations show how sample size would change under stated hypothetical planning assumptions; they do not establish what the original trial planned or whether the observed study had a particular probability of detecting an effect.

How should missing data and populations be considered?

The primary endpoint description states that missing data were imputed using last observation carried forward. This method carries a participant’s last recorded value forward to represent a later missing value. General statistical explanation: this can be useful as a stated convention, but it relies on assumptions about what the missing measurement would have been and can affect estimates if those assumptions are unsuitable. The registry does not report sensitivity analyses for alternative missing-data assumptions.

The primary analysis population required at least one dose through inclusion in the safety sample, correct randomization according to the Urodynamic Adjudication Board, and valid baseline and on-treatment urodynamic measurements. This means the primary estimate pertains to that defined analysis population. The registry does not report enough detail to assess the reasons for every exclusion or the effect of those exclusions on the result.

11. Confidence Intervals and Precision

The primary re-calculated mean difference is 8.045 mL for vardenafil minus placebo, with a 95% confidence interval from -16.99 to 33.08. The range includes zero and extends to values on either side, so the estimate does not precisely determine the direction of the group difference. The interval is more informative than the point estimate alone because it displays a range of effects compatible with the summary data and the calculation’s assumptions.

The sponsor’s ANCOVA estimate is -8.045 mL for placebo minus vardenafil, with a 95% confidence interval from -33.194 to 17.104. This is the same contrast direction as reversing the order used for the simple re-calculation. The confidence intervals are not identical, consistent with the distinction between the model-based sponsor analysis and the unadjusted calculation. The registry reports no discrepancy flag, and the sponsor’s analysis remains the reported trial analysis.

As a general statistical explanation, a confidence interval’s width reflects both the amount of information and the variability in the data, along with the analysis method. A wide interval leaves more uncertainty about the magnitude of the group difference; it should not be read as proof that all values within it are equally likely. Nor does an interval that includes zero establish that the groups are equivalent. The registry record does not report an equivalence margin or a clinically important difference for this endpoint.

The primary group summaries are based on 122 participants in the vardenafil group and 136 in the placebo group. The interval describes uncertainty for the analyzed population and method, not certainty about each individual outcome. Missing measurements were handled using last observation carried forward, and the registry record does not report sensitivity analyses showing how much the estimate might change under other missing-data assumptions.

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 sample-size illustrations translate an observed effect into hypothetical planning requirements under stated assumptions. For these continuous outcomes, the figures are participants per arm, not total event counts. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column means the hypothetical study would have an 80% chance of detecting the specified effect at the stated significance level if the planning assumptions and effect were correct. The 90% power column describes the corresponding hypothetical chance at the higher power target. These are planning quantities, not guarantees for a future study. The registry’s original design assumptions and sample-size justification are not reported in the registry record.

Each row considers planning for 100%, 75%, or 50% of the observed effect. A smaller target effect generally requires more participants per arm to distinguish it from random variation, which is why the participant requirements increase as the assumed effect gets smaller. The plotted curve can be read as the same relationship across a range of assumed effects: weaker target effects require larger planned groups under the calculation assumptions.

These illustrations use the effect estimated in this study, so they should not be treated as evidence that the original trial was designed around that effect. This is not observed power. The registry record does not report the trial’s original assumptions, recruitment target rationale, or planned power calculation.

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 = 8.045; pooled standard deviation σ = 102.421.
2. n = 2 × (1.96 + 0.842)² × 102.421² / 8.045² = 2,544.3, rounded up to 2,545 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 <- 8.045                      # observed difference in means
sigma <- 102.421068375251                     # 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(478881)
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 = 2,545 (80% power), 3,407 (90% power)
 75% of observed effect: n per arm = 4,524 (80% power), 6,056 (90% power)
 50% of observed effect: n per arm = 10,178 (80% power), 13,625 (90% power)
power.t.test: 2545.2 
Simulated power at n = 2,545 per arm: 0.799 (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

The registry reports the sponsor’s primary analysis as ANCOVA, with a mean difference of -8.045 mL for final values and a 95% confidence interval from -33.194 to 17.104. The sponsor’s contrast is placebo minus vardenafil. The simple re-calculation uses the opposite direction, vardenafil minus placebo, and gives 8.045 mL with a 95% confidence interval from -16.99 to 33.08. The sign changes because the group order is reversed.

The sponsor reports a p-value of 0.529, while the simple unadjusted re-calculation gives 0.529. These estimates are close, but they are not interchangeable: the sponsor’s ANCOVA is a model-based analysis, whereas the re-calculation uses posted summary statistics without adjustment. The registry does not flag a discrepancy between the reported and recalculated findings. Accordingly, the sponsor’s reported analysis is the trial result, and the recalculation is supplementary statistical context rather than a replacement for it.

Both analyses yield confidence intervals that include zero. This describes the uncertainty in the estimated group contrast; it does not establish equivalence or answer whether a difference would be clinically important. The registry record does not report a clinical-importance threshold for the endpoint.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports ten outcome measures and ten analyses, including the primary endpoint and secondary outcomes. It does not report a statistical plan describing how the family of outcomes was handled, whether hypotheses were ordered, or whether p-values were adjusted for multiple comparisons. This matters because examining multiple endpoints can increase the chance of at least one apparently unusual result even when there is no underlying effect. General statistical explanation: multiplicity procedures help control that risk, but the appropriate approach depends on the study’s aims and prespecified analysis plan.

The primary endpoint description says missing measurements were imputed using last observation carried forward. This approach uses a participant’s most recent available measurement as the imputed value for a later missing measurement. General statistical explanation: the method can be sensitive to assumptions about how outcomes would have changed after the last measurement. The registry does not report sensitivity analyses, alternative imputation methods, or a detailed account of the amount and pattern of missing primary outcome data.

The primary analysis population is defined as a modified intention-to-treat group: participants in the safety sample who were randomized correctly according to the Urodynamic Adjudication Board and had valid baseline and on-treatment urodynamic measurements. The registry notes that a stated number is not identical to another number, but the description is incomplete. The reason for the qualification and further details about exclusions are not reported in the registry record.

Enrollment was 397, while the primary endpoint summaries include 122 vardenafil participants and 136 placebo participants. These counts refer to different stages or analysis definitions, and the registry record does not explain the difference in enough detail to attribute it to specific causes. Therefore, the reported estimate should be understood as applying to the defined analysis population, with uncertainty about how exclusions and missing data may affect generalizability.

16. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (0.5%), angina unstable (0.5%), coronary artery disease (0.5%), vision blurred (0.5%), diarrhoea (0.5%).

The registry reports serious adverse events in 4 participants in the vardenafil group and 4 participants in the placebo group; the listed at-risk count is 198 in each group. It also lists serious-event terms, each with a reported frequency of 0.5%: angina pectoris, angina unstable, coronary artery disease, vision blurred, diarrhoea, and wrist fracture. The record does not establish from these entries whether any listed terms occurred in the same participant.

For other adverse events, the registry reports 78 affected participants in the vardenafil group and 39 in the placebo group, with 198 at risk in each group. These are counts as recorded, not evidence by themselves that the study drug caused an event or that a difference is statistically reliable. The registry does not report death counts. The listed safety summaries should be interpreted within the recorded trial population and follow-up; further detail about event severity, timing, and attribution is not reported in the registry record.

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

The primary result describes a comparison of average change in a urodynamic measure between randomized groups over up to 6 weeks. The unadjusted estimate is 8.045 mL for vardenafil minus placebo, and its 95% confidence interval ranges from -16.99 to 33.08. The sponsor’s ANCOVA result uses the reverse contrast and reports a 95% confidence interval from -33.194 to 17.104. Both intervals include zero and leave uncertainty about the direction and size of the difference.

This does not establish that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether plausible differences fall within that margin; such a margin is not reported in the registry record. Nor does the result establish that the treatment does or does not work. It is a statistical description of the endpoint, comparison, analysis population, and follow-up recorded in this trial.

The endpoint is a bladder volume measured during urodynamic assessment. It is not the same as a direct measure of how participants felt, daily functioning, or every aspect of overactive bladder. The registry lists several secondary outcomes that address other measures, but their presence does not make the primary endpoint a comprehensive assessment of all possible outcomes.

The interpretation is also limited to the modified intention-to-treat population and the specified 6-week treatment period. The registry record does not report the original sample-size justification, a clinical-importance threshold, detailed missing-data sensitivity analyses, or the complete multiplicity plan. Those omissions constrain conclusions about how the estimate should be weighed beyond its reported statistical uncertainty.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be read without its confidence interval. The primary group summaries differ, but the interval around their contrast spans values in both directions. The result therefore communicates both an estimated magnitude and substantial uncertainty about the underlying group difference.

It also illustrates how two legitimate presentations can use opposite contrast directions. The sponsor reports placebo minus vardenafil, while the simple re-calculation reports vardenafil minus placebo. The signs differ, but the group ordering explains that reversal. Reading the contrast definition alongside the estimate prevents a sign change from being mistaken for a conflicting result.

A further statistical issue is the distinction between a sponsor’s adjusted analysis and a simple summary-statistic re-calculation. The latter can help readers understand the scale of the posted data, but it does not replace the trial’s reported ANCOVA. The analysis population, LOCF imputation, and incomplete reporting of the analysis plan also matter when assessing how broadly to interpret the finding.

Finally, the trial reports several secondary measures and safety counts. They provide context, but multiple outcomes require care in interpretation, and isolated secondary results should not be treated as confirmatory when the multiplicity plan is not reported. Together, these features make the study a useful example of interpreting estimate direction, model choice, uncertainty, missing-data handling, and multiple outcomes without reducing the result to 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 primary endpoint is an objective urodynamic measure, but the registry does not report a threshold for a clinically important difference. Statistical uncertainty can therefore be described, while the importance of a particular difference to participants cannot be determined from the endpoint estimate alone.

The primary analysis population is defined by safety, randomization adjudication, and availability of valid baseline and on-treatment urodynamic measurements. The registry reports enrollment of 397 but gives primary summary counts of 122 and 136. It does not report enough detail to explain the difference, characterize the excluded participants, or assess the effect of exclusions on the comparison.

Missing primary endpoint data were handled using last observation carried forward. The registry does not report the amount or pattern of missing data, alternative imputation analyses, or sensitivity analyses. The method’s assumptions therefore cannot be evaluated against other approaches from the registry record.

The sponsor’s ANCOVA model is not fully described: the covariates and detailed model specification are not reported in the registry record. The record also does not report the original sample-size rationale, a complete prespecified statistical plan, or how multiplicity across the listed outcomes was addressed. The quantified secondary results cover only some of the listed outcomes; detailed results for the remaining outcomes are not reported in the registry record.

Follow-up for the intervention was 6 weeks, so the registry results describe that treatment period. The information does not establish longer-term outcomes. These limitations qualify interpretation of the estimates and do not, on their own, determine the direction of any underlying effect.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function — NCT00478881.
• Registry record last updated 2014-12-11; status last verified 2014-11.
• Results first posted 2009-12-24.
• 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.

23. Record Summary

The registry describes a completed Phase 2 randomized, triple-masked, parallel-group study of vardenafil hydrochloride 10 mg twice daily versus matching placebo for 6 weeks in participants with overactive bladder or detrusor overactivity. Enrollment was 397. The primary outcome was change from baseline in bladder volume at first detrusor contraction, measured in mL, with missing data handled using last observation carried forward.

The sponsor reported an ANCOVA mean difference of -8.045 mL for placebo minus vardenafil, with a 95% confidence interval from -33.194 to 17.104 and a reported p-value of 0.529. The simple unadjusted re-calculation gives 8.045 mL for vardenafil minus placebo, with a 95% confidence interval from -16.99 to 33.08. Both intervals include zero. Secondary outcomes and safety events are also listed, while details of the original sample-size justification, full statistical plan, and multiplicity handling are not reported in the registry record.