A Study of Tadalafil in Men With Benign Prostatic Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tadalafil in Men With Benign Prostatic Hyperplasia (NCT00970632), a randomized phase 3 study. The primary outcome is Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-design study. The official title describes it as global and multicenter, and the registry lists triple masking. It compared daily tadalafil, daily tamsulosin and placebo over 12 weeks in men with signs and symptoms of benign prostatic hyperplasia. The registry records an enrollment of 511 and a completed status.

The three groups with posted primary outcome results were placebo, tadalafil 5 mg and tamsulosin 0.4 mg. The placebo regimen used both a placebo tablet and a placebo capsule. Tadalafil was paired with a placebo capsule, while tamsulosin was paired with a placebo tablet. These descriptions indicate how the study accommodated the different formulations; further details about how masking was maintained are not reported in the registry record.

The primary outcome was change from baseline in total IPSS at 12 weeks. The reported group estimates are least-squares means from an analysis of covariance, rather than simple raw averages. The listed analysis population included randomized participants who began study medication and had baseline data and at least one post-baseline measurement. The outcome description says the endpoint was Week 12 or the last post-baseline value carried forward.

The registry also lists secondary outcomes covering total symptom score at an earlier visit, symptom subscores, nocturia, quality of life, a modified symptom score and the impact of benign prostatic hyperplasia. The registry record does not report the original sample-size justification or the trial’s original design assumptions. Further detail about recruitment, adherence, withdrawals and the conduct of masking 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: Period 1: Screening and 4-week washout of benign prostatic hyperplasia (BPH), overactive bladder (OAB), and/or erectile dysfunction (ED) treatments. Period 2: 4-week, single-blind, placebo lead-in to assess compliance and establish baseline levels. Period 3: Randomization to treatment (placebo, tadalafil 5 mg, or tamsulosin 0.4 mg for 12 weeks).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.

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 Total International Prostate Symptom Score (IPSS) at 12 Weeks, measured over Baseline, 12 weeks.

The primary endpoint is change from baseline in total International Prostate Symptom Score at 12 weeks. The score combines responses to seven component questions, each scored from 0 to 5, for a total range of 0 to 35 points. Higher numerical scores represent greater symptom severity. A negative change therefore indicates a lower measured score at follow-up than at baseline; it should be understood as a change on this questionnaire, not as a complete account of a participant’s health.

The registry reports least-squares mean changes estimated using ANCOVA. The stated model adjusted for treatment group, region, centered baseline score, the interaction between centered baseline score and treatment, and the interaction between treatment and region. Adjustment can account for specified baseline and design factors when estimating group means, rather than relying only on unadjusted group averages.

Using a defined symptom scale makes it possible to compare average changes across randomized groups at a specified follow-up. The 12-week measure is the primary endpoint in the registry record, while earlier total-score change and symptom domains are listed as secondary outcomes. The registry’s description allows the 12-week endpoint to use the last post-baseline value carried forward when Week 12 is unavailable. The extent to which that occurred, and its effects on the estimates, are not reported in the registry record.

7. Results Posted in the Registry

• Tadalafil 5 mg: mean -6.30 versus -4.20 on control; difference -2.10 (95% CI -3.49 to -0.71), standardized effect d = -0.32; z-test p = 0.003.
• Tamsulosin 0.4 mg: mean -5.70 versus -4.20 on control; difference -1.50 (95% CI -2.89 to -0.11), standardized effect d = -0.23; z-test p = 0.034.

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 Total International Prostate Symptom Score (IPSS) at 4 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:
  • Tadalafil 5 mg: mean -5.50 versus -3.30 on control; difference -2.20 (95% CI -3.31 to -1.09), standardized effect d = -0.43; z-test p = <0.001.
  • Tamsulosin 0.4 mg: mean -5.70 versus -3.30 on control; difference -2.40 (95% CI -3.51 to -1.29), standardized effect d = -0.47; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tadalafil 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tamsulosin 0.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 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:
  • Tadalafil 5 mg: mean -2.20 versus -1.60 on control; difference -0.60 (95% CI -1.15 to -0.05), standardized effect d = -0.23; z-test p = 0.034.
  • Tamsulosin 0.4 mg: mean -2.20 versus -1.60 on control; difference -0.60 (95% CI -1.15 to -0.05), standardized effect d = -0.23; z-test p = 0.034.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tadalafil 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tamsulosin 0.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 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:
  • Tadalafil 5 mg: mean -4.10 versus -2.60 on control; difference -1.50 (95% CI -2.33 to -0.67), standardized effect d = -0.38; z-test p = <0.001.
  • Tamsulosin 0.4 mg: mean -3.50 versus -2.60 on control; difference -0.90 (95% CI -1.73 to -0.07), standardized effect d = -0.23; z-test p = 0.034.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tadalafil 5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tamsulosin 0.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes spanning total IPSS at an earlier visit, storage and voiding subscores, nocturia, quality of life, a modified symptom score and the Benign Prostatic Hyperplasia Impact Index. Taken together, these outcomes add context about different aspects of symptoms and their reported impact. They are related to the primary total score, but measure distinct components or time points and should not be treated as interchangeable measures of the same endpoint.

The posted summaries show that secondary outcomes were analyzed across several visits and domains. Some comparisons have reported ANCOVA results, while the accompanying simple recalculations do not always match the sponsor’s reported p-values. As with the primary endpoint, the sponsor’s reported analyses take precedence over unadjusted recalculations. The secondary results can be considered alongside the primary finding as contextual evidence, but they do not independently establish a broader pattern of effects.

There are 17 outcome measures listed and 30 analyses in the registry data, with 16 secondary outcomes posted. The number of outcomes and comparisons matters for interpretation because repeated testing increases the chance of at least one apparently unusual result when many hypotheses are examined. The registry record does not report a multiplicity adjustment, a prespecified testing hierarchy or how secondary outcomes were prioritized. Unadjusted secondary p-values therefore carry less weight than a clearly specified primary analysis, particularly when considered one at a time.

It is also important not to infer that agreement across related questionnaire measures constitutes independent replication: the measures may share information because they concern overlapping symptoms or participant reports. The registry does not report correlations among the outcomes. The secondary findings are best treated as supportive descriptive context, with uncertainty about multiplicity and analysis planning, rather than as a set of definitive separate conclusions.

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

• Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks
• Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks
• Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks.
• Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks
• Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks
• Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week
• Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks
• Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks

9. Statistical Interpretation

10. Statistical Methods Explained

The registry’s primary outcome is a continuous score, and the reported group values are least-squares mean changes. The outcome description specifies ANCOVA, with adjustment for treatment group, region, centered baseline score, baseline-by-treatment interaction and treatment-by-region interaction. The results are therefore adjusted estimates under that model. The registry does not report additional details about model diagnostics, the choice of covariance structure or sensitivity analyses.

What does an adjusted mean represent?

General explanation: A least-squares mean is an estimate from a statistical model, not necessarily the arithmetic average of the observed values in a group. It represents a model-based group mean after accounting for the covariates and interactions included in the analysis. Adjustment can improve comparability when those terms are relevant, but it does not automatically remove bias from unmeasured factors or make missing data irrelevant. In this trial, the listed adjustment terms are described in the registry; further details of model implementation are not reported in the registry record.

What does a mean difference describe?

General explanation: A mean difference contrasts two group means on the outcome’s original scale. Here, the registry’s reported difference in least-squares means is the active group’s estimated change relative to placebo. A negative difference is consistent with a more negative change in the active group. It describes an average contrast, not the range of individual responses, and it does not by itself establish the practical importance of that contrast.

How should the recalculations be understood?

The recalculated comparisons use the posted group-level estimates and standard errors to form simple, unadjusted comparisons. The pooled standard deviations used for the calculations are approximate, because the posted group dispersion is a standard error rather than a standard deviation. The resulting estimates and intervals are not a reconstruction of the sponsor’s ANCOVA model. When recalculated and sponsor results differ, the sponsor’s own analysis takes precedence. In this trial, recalculated point estimates match the sponsor’s reported differences, while the p-values do not match exactly.

General explanation: A standard error describes the estimated sampling uncertainty of a mean, while a standard deviation describes variability among observations. Converting one into the other requires information about the relevant sample size and assumptions about the data. A pooled standard deviation is used in some unadjusted comparisons to represent within-group variability across the two groups. When it is estimated indirectly from rounded summary statistics, the resulting standardized effect and interval are approximate. They should not be confused with the fitted-model uncertainty from ANCOVA.

What does a p-value contribute?

General explanation: A p-value measures how incompatible data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. Interpretation also depends on the analysis plan, the number of outcomes and comparisons, and whether the reported test was prespecified. The registry record does not report whether a multiplicity adjustment was used for the family of outcomes and comparisons.

The sponsor’s primary p-values are from the reported ANCOVA analyses. The recalculated p-values are explicitly unadjusted and use a simpler calculation from summaries. The difference between these inferential results is a reason to keep the analysis methods distinct, rather than selecting whichever p-value appears more favorable. The registry does not report the sponsor’s full statistical analysis plan, so the exact planned hierarchy or handling of multiple comparisons is not reported in the registry record.

Why can over-dispersion matter?

General explanation: Over-dispersion occurs when observations vary more than a model’s assumed distribution allows. If a model understates variability, standard errors can be too small and intervals too narrow; if it overstates variability, inference can become less precise. This concept is especially relevant to outcomes whose variability is not adequately captured by a simple model. The primary IPSS endpoint is treated as continuous in the registry, and no over-dispersion assessment is reported. It would therefore be inappropriate to assert that over-dispersion was present or that a particular correction was needed.

The registry gives the analysis population as randomized participants who started study medication and had non-missing baseline information and at least one post-baseline measurement. This is not identical to a description of all randomized participants regardless of treatment start or availability of outcome data. The numbers contributing to the primary estimates are listed by group, but reasons for exclusions, the amount of missing outcome data and comparisons between included and excluded participants are not reported in the registry record.

The endpoint description says that the Week 12 value or the last post-baseline value carried forward was used. That statement identifies a method for forming the endpoint when the Week 12 value is unavailable, but the registry does not report how often this occurred or whether other missing-data sensitivity analyses were performed. General statistical caution applies: carrying a previous score forward assumes that the carried value is an appropriate stand-in for the unobserved endpoint, an assumption that may not hold for every participant. The registry record does not report an assessment of that assumption.

11. Confidence Intervals and Precision

The sponsor reports adjusted primary mean differences of -2.1 for tadalafil versus placebo and -1.5 for tamsulosin versus placebo. The posted sponsor analyses give p-values but no confidence limits. The registry record therefore does not report adjusted confidence intervals for these primary contrasts.

The simple recalculations give an unadjusted interval for each comparison. Both intervals exclude zero, indicating that the calculated range of values under that approximate method does not include no mean difference. These intervals are based on posted summary statistics and approximate pooled variability; they are not confidence intervals from the sponsor’s ANCOVA. Their precision should be interpreted accordingly. The sponsor’s analysis takes precedence where the two analyses differ.

General explanation: A confidence interval describes a range of values compatible with a statistical model and the observed data at a stated confidence level. It gives information about precision that a point estimate alone cannot provide. A narrower interval indicates more precise estimation under the model; a wider interval indicates greater uncertainty. An interval is not a guarantee that the true value lies within its endpoints, and it does not by itself establish clinical importance.

The registry’s absence of confidence limits for the adjusted analyses limits direct assessment of their precision. The reported standard errors for the group least-squares means are not a substitute for the uncertainty of the adjusted between-group contrast. The recalculated intervals can offer a transparent, rough comparison based on available summaries, but they cannot resolve that limitation or reproduce the sponsor’s model-based uncertainty.

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 illustrations describe hypothetical sample sizes for detecting fractions of the observed effect. They are not the trial’s original design calculations: the original sample-size justification and assumptions are not reported in the registry record. For these continuous outcomes, figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect.

The column for 80% power gives the estimated number of participants per arm under those assumptions for an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses the same interpretation with a higher target chance of detection. These are design-planning quantities, not guarantees that a future study will produce a particular result. The planning illustrations use an observed estimate as their starting point, so they are sensitive to how representative that estimate is.

The rows for 100%, 75% and 50% of the observed effect ask what sample size would be needed if the effect to detect were the full observed effect or a smaller fraction of it. A smaller target effect requires more participants per arm under the same assumptions. The displayed curve conveys the same planning relationship across its plotted values; it should be read as a design illustration, not as evidence about what occurred in this completed study.

These figures are not observed power. Observed power is not a useful substitute for interpreting the estimates and their uncertainty after a trial is complete. The reported sample-size illustrations are best used to understand how design requirements change with the assumed effect size and target power, not to judge whether the completed study was adequately powered based on its observed result.

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 = -2.100; pooled standard deviation σ = 6.548.
2. n = 2 × (1.96 + 0.842)² × 6.548² / -2.100² = 152.6, rounded up to 153 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 <- -2.1                      # observed difference in means
sigma <- 6.54792841812698                     # 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(970632)
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 = 153 (80% power), 205 (90% power)
 75% of observed effect: n per arm = 272 (80% power), 364 (90% power)
 50% of observed effect: n per arm = 611 (80% power), 818 (90% power)
power.t.test: 153.6 
Simulated power at n = 153 per arm: 0.798 (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 sponsor reports ANCOVA comparisons of each active group with placebo. At 12 weeks, the reported difference in least-squares means is -2.1 for tadalafil and -1.5 for tamsulosin. The corresponding reported p-values are 0.001 and 0.023. No confidence limits are included for these reported analyses.

The simple recalculations from posted group summaries reproduce the two reported point estimates, but give unadjusted p-values of 0.003 and 0.034. This difference is consistent with the fact that the calculations do not reproduce the sponsor’s adjusted ANCOVA. The recalculated variability is approximate, and the calculations do not use the full model specification or participant-level data.

Accordingly, the sponsor’s own analysis takes precedence for interpreting the registry’s primary result. The recalculations serve as a separate, transparent check using summary statistics and should not be used to overwrite or combine with the adjusted tests. The registry record does not include sufficient detail to reconstruct the sponsor’s full analysis independently.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists multiple secondary outcomes and analyses. It does not report whether the sponsor adjusted for multiplicity, set a hierarchy of tests or controlled a particular family-wise error rate. Without those details, the statistical status of individual secondary p-values cannot be fully assessed. Repeated testing can increase the chance of a nominally notable result arising by chance, so secondary findings warrant more caution than a single prespecified primary comparison.

The primary analysis population included randomized participants who started study medication and had non-missing baseline information and at least one post-baseline measurement. The registry does not report how many randomized participants were excluded from that population or why. Nor does it report missingness by visit, reasons for missing measurements, or a comparison of participants with and without observed follow-up.

The outcome description specifies an endpoint at Week 12 or the last post-baseline value carried forward. The registry record does not report how many participants’ endpoint values were carried forward, whether other imputation methods were considered, or whether sensitivity analyses tested the effect of missing data assumptions. The original sample-size justification and interim-analysis plan are also not reported in the registry record.

General explanation: Missing-data methods rely on assumptions about how observed and unobserved outcomes are related. Carrying a prior observation forward can be simple to implement, but it may not reflect a participant’s unobserved score at the endpoint. Sensitivity analyses can explore whether conclusions change under alternative assumptions. The registry’s description alone is not enough to determine whether missingness materially affected these results or whether the analysis assumptions were appropriate for every participant.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tachycardia (0.6%), dyspepsia (0.6%), dizziness (0.6%), headache (0.6%), hyperhidrosis (0.6%).

The registry reports serious adverse events affecting 2 of 171 participants in the tadalafil group, 2 of 168 in the tamsulosin group and 0 of 172 in the placebo group. These are group counts in the posted safety data. The registry also lists tachycardia, dyspepsia, dizziness, headache, hyperhidrosis and flushing among the serious adverse event terms, each at 0.6%.

Other adverse events are reported for 39 of 171 participants receiving tadalafil, 40 of 168 receiving tamsulosin and 35 of 172 receiving placebo. Death counts are not reported in the registry record. The displayed counts describe events recorded during this study; they do not by themselves establish whether an event was caused by a study drug or permit a complete comparison of risk.

General explanation: Safety counts need to be read in light of the group sizes, follow-up, event definitions and how events were collected. Small counts can be imprecise, and a count of zero does not demonstrate that an event cannot occur. Further details on event timing, severity beyond the serious-event classification and attribution are not reported in the registry record.

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

The posted primary results describe average changes in total IPSS over the study period for the defined analysis population. The group least-squares means decreased from baseline in all three groups, with larger negative changes reported for tadalafil and tamsulosin than for placebo. The sponsor’s ANCOVA comparisons report mean differences of -2.1 and -1.5, respectively. These are group-level estimates on the symptom-score scale, not predictions of an individual participant’s experience.

The results do not establish the clinical importance of those differences. The registry does not report a threshold for a meaningful change, nor does it provide a distribution of individual responses or the proportion of participants meeting a response criterion. A mean can conceal variation: participants within the same group may have had different changes.

The findings also do not provide a direct reported comparison between tadalafil and tamsulosin. Each active group is compared with placebo in the posted primary analyses. The point estimates cannot substitute for a formal head-to-head test. In addition, the recalculated comparisons are approximate and unadjusted, while the sponsor’s ANCOVA is the reported primary analysis.

The study’s eligibility criteria, detailed participant characteristics, adherence, withdrawals and generalizability beyond the analyzed participants are not described in the registry record in the registry record. The result should therefore be read within the setting and analysis population that the registry documents, rather than assumed to apply equally to all men with benign prostatic hyperplasia. The results do not identify mechanisms, predict outcomes for an individual, or answer questions that were not measured in the listed outcomes.

General explanation: Statistical evidence about an average difference and evidence about clinical importance are related but distinct. Precision, the size of the estimate, measurement properties, participant priorities and the broader evidence base all matter when judging practical meaning. The registry results alone do not settle those broader questions.

18. Why This Trial Matters Statistically

This trial is statistically informative because it presents an adjusted primary analysis alongside group-level estimates for three randomized groups. The primary outcome is a defined continuous score, and the registry specifies the ANCOVA adjustment terms and the analysis population. Those details help readers understand what the reported estimates represent and which participants contributed to them.

It also illustrates why adjusted sponsor analyses and simple recalculations should be kept separate. The recalculated primary point estimates match the sponsor’s reported contrasts, while the unadjusted p-values differ from the reported ANCOVA p-values. Comparing the two makes the role of model specification visible without treating the simpler calculation as a replacement for the sponsor’s analysis.

The record also demonstrates the value of looking beyond a point estimate. The reported analyses do not include confidence limits, while approximate recalculated intervals can only provide a limited view of uncertainty. That distinction helps avoid attributing more precision to the adjusted result than the registry reports.

Finally, the many secondary outcomes and analyses highlight the importance of multiplicity and transparent analysis plans. A broad symptom assessment can provide useful context, but interpretation depends on how outcomes were prioritized and how repeated testing was handled. Those details are not reported in the registry record. Overall, this study offers a clear example of how design, outcome definition, model-based analysis, uncertainty and reporting completeness shape statistical interpretation.

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.

Several limitations arise from the registry record. It does not report confidence intervals for the sponsor’s adjusted primary comparisons, so their model-based precision cannot be directly assessed from the posted analyses. The simple recalculated intervals are approximate and unadjusted; they do not reproduce the sponsor’s ANCOVA. The discrepancy in p-values makes it especially important to give precedence to the sponsor’s reported analysis.

The record does not report the original sample-size justification, the sponsor’s full statistical analysis plan, the multiplicity approach, or whether interim analyses were planned or conducted. It also does not report how missing outcome data were distributed, how often the last-observation-carried-forward approach was used, or whether alternative missing-data analyses were performed. These omissions limit evaluation of analysis choices and robustness.

The stated analysis population requires participants to have started study medication and to have baseline and post-baseline data. The registry does not report reasons for not contributing to that population or comparisons between included and excluded randomized participants. The posted results therefore cannot, on their own, show whether exclusions or missing measurements could have affected the estimates.

The registry’s posted group summaries do not provide participant-level distributions, individual response patterns or a threshold for interpreting the clinical importance of score changes. The active-group results are comparisons with placebo, not a reported direct comparison between tadalafil and tamsulosin. Further details about participant characteristics, adherence, withdrawals, outcome assessment and safety-event attribution are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Tadalafil in Men With Benign Prostatic Hyperplasia — NCT00970632.
• Registry record last updated 2012-03-12; status last verified 2012-03.
• Results first posted 2011-12-23.
• 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 record describes a completed Phase 3 randomized, double-blind, placebo-controlled, parallel-design study in men with signs and symptoms of benign prostatic hyperplasia, with enrollment of 511. The primary endpoint was change from baseline in total IPSS at 12 weeks, analyzed using adjusted least-squares means from ANCOVA in a defined analysis population.

The sponsor reported mean differences versus placebo of -2.1 for tadalafil 5 mg and -1.5 for tamsulosin 0.4 mg, with p-values of 0.001 and 0.023. Simple recalculations match the point estimates but produce different unadjusted p-values; the sponsor’s analysis takes precedence. The registry also lists secondary symptom and impact outcomes, serious and other adverse event counts, and limitations in reporting of confidence intervals, multiplicity, missing data and the original sample-size rationale.