Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (NCT00384930), a randomized phase 2, phase 3 study. The primary outcome is Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis.

2. Clinical Question

The clinical question is whether symptom-score changes over the 12-week study period differed between placebo and any of the four tadalafil dose groups. Because the study included multiple doses, it could also assess whether the observed pattern was consistent with a dose response. That objective is part of the study description, not a numerical finding: the primary outcome results are not reported in the registry record. The registry lists additional symptom, quality-of-life, urinary-flow, global-assessment, and erectile-function outcomes, but their results are not reported in the registry record either. The clinical question is thus clear from the design and outcome definitions, while the registry information available for this analysis does not establish the size or precision of an observed effect.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, parallel-design, multinational study with five groups. Four groups received once-daily tadalafil at 2.5 mg, 5 mg, 10 mg, or 20 mg; the fifth received placebo. The study is classified as Phase 2 and Phase 3 and is marked completed. The reported enrollment is 1058. The stated treatment and assessment period for the study was 12 weeks.

The primary completion date is 2007-10, and the study start is listed as 2006-08. Eli Lilly and Company is named as the sponsor. These administrative details describe the trial record but do not establish how many participants completed follow-up, how many were included in each analysis, or how participants were distributed across the five groups. Those details are not reported in the registry record.

Randomization is intended, in general, to reduce systematic differences between treatment groups at the outset. Double masking is intended, in general, to limit the influence of treatment knowledge on participants’ reports and study assessments. A parallel design assigns participants to a group that remains their assigned group during the study, rather than having participants cross between treatments. These general features characterize the planned comparison, but the specific sequence-generation, concealment, and masking procedures are not reported in the registry record.

The study’s multi-dose structure allows comparisons of several tadalafil doses with placebo. It also means that interpretation depends on knowing which comparisons were prespecified and how the analysis handled multiple doses and outcomes. Those details, including a full statistical analysis plan, are not reported in the registry record. The design and enrollment alone cannot supply the missing outcome estimates or their uncertainty.

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: Prior to randomization, participants had a 1-4 week Screening/Wash-out Period, followed by a 4 week Placebo Run-In Period. 1813 participants were screened with 755 screen failures, and 1058 participants randomized. The two participants who did not receive study drug were not included in the baseline demographics table.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary analysis was performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.

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 to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis, measured over Baseline and 12 weeks.

The primary endpoint is change from baseline to the 12-week endpoint in the International Prostate Symptom Score (IPSS). The registry describes IPSS as a measure of the severity of benign prostatic hyperplasia symptoms and response to therapy. Its total score is formed by summing responses to seven component questions. The stated scale runs from 0 to 35, with 0-7 described as mildly symptomatic, 8-19 as moderately symptomatic, and 20-35 as severely symptomatic.

A change score expresses how a participant’s recorded score at follow-up differs from the baseline score. In general, using a change endpoint focuses the comparison on movement over the assessment period while accounting for each participant’s starting measurement. The endpoint is relevant to the study’s symptom-focused question because it uses a score specifically defined in the registry as assessing symptom severity. The registry specifies baseline and 12 weeks as the timeframe.

The primary analysis is described as using the mean and standard deviation. The record says the analysis was performed on an intent-to-treat basis, using data from subjects with baseline and at least one postbaseline observation, with last observation carried forward. Numerical group means, standard deviations, treatment contrasts, and confidence intervals for the primary endpoint are not reported in the registry record. Consequently, the outcome definition can be explained, but the magnitude and precision of the observed change cannot be assessed from the registry information available for this analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measure and describes the analysis parameter as the mean, with standard deviation as the dispersion measure. In general, a mean summarizes the central value of a set of measurements, while a standard deviation describes how spread out individual measurements are around that mean. These summaries are useful for describing group outcomes, but they do not alone quantify the uncertainty in a treatment-group comparison. The registry’s numerical summaries and comparison estimates are not reported in the registry record.

What does a change score represent?

The endpoint is the change from baseline to the 12-week endpoint in total IPSS. A change score is a within-participant comparison of a follow-up value with that participant’s baseline value. In a randomized study, comparing average changes between groups can describe how the groups’ outcomes moved over the study period. In general, interpretation requires knowing the group estimates and how uncertainty around their difference was assessed. Those estimates and uncertainty measures are not reported in the registry record, so the magnitude of a group contrast cannot be stated.

The IPSS total is derived by summing responses to seven component questions. Its registry-defined range is 0 to 35, with categories of 0-7 for mildly symptomatic, 8-19 for moderately symptomatic, and 20-35 for severely symptomatic. Those categories help describe the scale’s stated interpretation. They do not reveal how participants in this trial scored, and the registry information available for this analysis does not report the primary outcome values.

What does the analysis population mean?

The primary analysis is described as intent-to-treat, with data from subjects who had a baseline and at least one postbaseline measurement used in the analysis. In general, an intent-to-treat approach aims to preserve the comparison created by random assignment, rather than defining groups solely by treatment received or later adherence. The record’s additional requirement for an observed postbaseline measurement means the analysis set is described using an availability criterion as well. The number of participants meeting that criterion, and the number analyzed in each group, are not reported in the registry record.

The record also specifies last observation carried forward (LOCF). In general, LOCF substitutes a participant’s last available postbaseline observation for a later missing measurement. This creates an analysis value where a later measurement is missing, but it relies on an assumption that carrying the earlier value forward is an acceptable representation of the unobserved later outcome. That assumption may not fit every participant’s trajectory. The registry does not report how many observations were missing, when missingness occurred, or whether additional missing-data analyses were conducted.

How should the design and multiple outcomes be read?

Randomized assignment, double masking, placebo control, and a parallel structure are features of the design. In general, randomization can help balance measured and unmeasured baseline factors across groups, while masking can reduce some influences of treatment awareness on reporting and assessment. These design features do not remove the need to examine outcome estimates, uncertainty, missing data, and analysis choices. Details of sequence generation, allocation concealment, and masking procedures are not reported in the registry record.

The registry lists 10 outcome measures and 37 analyses. Multiple doses and multiple outcomes create a general multiplicity issue: when many comparisons are considered, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for the family of tests. The registry record does not report whether an adjustment or a prespecified hierarchy was used. Because the primary results are not reported in the registry record, the consequences of any multiplicity approach cannot be evaluated.

What are the planning illustrations?

General sample-size planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Their stated effect to detect is a fraction of the observed effect. Such illustrations are planning calculations, not observed power and not evidence that the trial was designed using those assumptions. They do not establish the original design rationale or the number of participants assigned to each arm. The trial’s own sample-size justification is not reported in the registry record, and numerical planning illustrations cannot be described from the information available for this analysis.

In general, over-dispersion means that observed variability is greater than assumed by a model. If a calculation assumes a narrower spread than the data support, its uncertainty estimates or planning implications may be too optimistic. The registry identifies the primary outcome as a mean with standard deviation, but it does not report numerical variability or an analysis addressing over-dispersion. No additional model-specific assumptions or diagnostic results are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study includes five groups, with four tadalafil doses and placebo, and the registry lists 10 outcome measures and 37 analyses. In general, testing several doses across several outcomes raises a multiplicity question: the more comparisons considered, the more important it is to know which were planned as primary and whether any adjustment or testing hierarchy was used. The registry identifies a primary endpoint, but a multiplicity adjustment, hierarchy, or detailed statistical analysis plan is not reported in the registry record. The primary result itself is also not reported in the registry record, so the reported evidence cannot be evaluated against any such plan.

For the primary analysis, the registry states that participants with baseline and at least one postbaseline observation were included, and that last observation carried forward was used. The number with missing measurements, the timing and reasons for missingness, and the number analyzed in each group are not reported in the registry record. It also does not report sensitivity analyses using alternative missing-data assumptions. In general, carrying the last observation forward gives a value for a later missing measurement, but that value may not represent the outcome that would actually have been observed.

The record calls the primary analysis intent-to-treat but defines the analysis data as requiring baseline and at least one postbaseline measurement. The count of randomized participants excluded from that analysis, if any, is not reported in the registry record. Interim analyses, stopping rules, and the statistical plan are not reported in the registry record. These omissions restrict assessment of how completely the analysis followed randomized assignment and how the outcome analyses were specified.

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

The record establishes that the trial was designed to compare four once-daily tadalafil doses with placebo over 12 weeks in men with signs and symptoms of benign prostatic hyperplasia. It also defines the primary endpoint as change in total IPSS and describes the analysis population and LOCF approach. These registry entries clarify the question and methods, but they do not reveal the primary outcome result.

The primary numerical comparison, its uncertainty, and its statistical interpretation are not reported in the registry record. Accordingly, the record does not support a statement about how much scores changed in any group, whether groups differed, or how precisely a difference was estimated. The stated dose-response objective does not by itself establish a dose-response finding. The secondary outcome definitions likewise do not establish results for those measures.

General statistical interpretation distinguishes an estimate from its precision. An estimated group contrast describes the observed difference under a specified analysis; an uncertainty interval indicates how much the estimate may vary under the analysis assumptions. Neither can be reconstructed without the relevant outcome data and analysis results. The enrollment of 1058 is not enough to infer an outcome effect or its precision, and it is not a substitute for reported results.

The adverse-event record lists serious and other affected counts for each group, but the numbers at risk are not reported in the registry record. The counts therefore should not be read as rates or used to infer comparative risk. Death counts are not reported in the registry record. Several serious-event terms are listed at 0.5% each, but the registry information available for this analysis does not provide the context needed to interpret those percentages as arm-specific or comparative estimates.

In short, the registry supports description of the trial design, endpoint, and stated analysis approach. It does not support a conclusion about the size, direction, or precision of the primary outcome difference, nor a comparative safety conclusion based on rates. Those boundaries reflect the results and denominators not reported in the registry record.

12. Why This Trial Matters Statistically

This study is statistically notable for its five-group design: placebo was compared with four tadalafil dose levels. That structure makes it possible in principle to examine multiple dose-versus-placebo contrasts and the stated dose-response objective. It also makes the analysis plan important. Readers need to know how primary and secondary outcomes, dose comparisons, and multiplicity were handled to interpret a collection of results coherently. Those details are not reported in the registry record.

The primary outcome is a continuous symptom score measured at baseline and at 12 weeks. The record specifies a mean and standard deviation and describes a change-from-baseline analysis. This makes the target measurement clear, while the absence of numerical results prevents evaluation of the estimated changes and their uncertainty. The enrollment total of 1058 describes the overall study size but does not tell readers the allocation by arm or the analysis counts.

The stated use of an intent-to-treat analysis with a baseline and at least one postbaseline observation, together with LOCF, also highlights the importance of transparency about missing data. In general, missing-data methods can influence estimates when follow-up observations are unavailable. The number and pattern of missing observations and any sensitivity analyses are not reported in the registry record.

Finally, the study illustrates why a complete registry record needs more than a design description. Clear outcome definitions and analysis-population notes help identify what was intended, but estimates, uncertainty measures, and complete analysis details are needed to judge the posted evidence. In this record, the design and methods are described more fully than the primary numerical outcome results, which are not reported in the registry record.

13. 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 principal limitation for interpreting this trial from the registry information available for this analysis is that numerical results for the primary endpoint are not reported in the registry record. Without group summaries and a treatment contrast, the observed symptom-score pattern and its precision cannot be described. The record also says the primary outcome has several categories or time points and is not reduced to one comparison, so a single summary contrast is not available.

Additional details needed to assess the analysis are not reported in the registry record. These include group allocation counts, numbers analyzed by group, the amount and pattern of missing data, the handling of missingness beyond LOCF, sensitivity analyses, and the full statistical analysis plan. Randomization-sequence generation, allocation concealment, masking procedures, interim analyses, and stopping rules are also not reported in the registry record. Their absence from the registry information available for this analysis should not be read as evidence that a procedure was or was not used.

The study lists several outcome measures and analyses, but an adjustment for multiplicity or a hierarchy among outcomes is not reported in the registry record. Numerical results for the secondary outcomes are not reported in the registry record either. The adverse-event information lacks numbers at risk by group, limiting rate-based comparisons. Death counts are not reported in the registry record. The top serious-event terms are listed at 0.5% each, but the available information does not establish the context needed for comparative interpretation.

Finally, the sample-size justification used for the original trial is not reported in the registry record. Planning illustrations based on observed effects are not a substitute for that justification and do not describe observed power. These limitations constrain the available statistical interpretation; they do not establish whether the trial was conducted well or poorly.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia — NCT00384930.
• Registry record last updated 2009-09-02; status last verified 2009-08.
• Results first posted 2009-08-19.
• 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.

17. Record Summary

The registry identifies NCT00384930 as a completed, randomized, double-blind, placebo-controlled, parallel-design, multinational study classified as Phase 2 and Phase 3. It reports enrollment of 1058 and a 12-week study of once-daily tadalafil at 2.5 mg, 5 mg, 10 mg, or 20 mg versus placebo in men with signs and symptoms of benign prostatic hyperplasia. Eli Lilly and Company is named as sponsor; the study start is listed as 2006-08 and primary completion as 2007-10.

The primary endpoint is change from baseline to the 12-week endpoint in total IPSS, described as a seven-question symptom score with a range from 0 to 35. The primary analysis is described as intent-to-treat, using participants with baseline and at least one postbaseline observation, with LOCF. The primary outcome results, group allocation counts, and detailed statistical analysis plan are not reported in the registry record. The record lists 10 outcome measures and 37 analyses.