A Study of Tadalafil in Men With Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED): 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 (BPH) and Erectile Dysfunction (ED) (NCT01937871), a randomized phase 3 study. The primary outcome is Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 12.

2. Clinical Question

The registry describes the study’s purpose as evaluating whether tadalafil could reduce signs and symptoms of BPH-LUTS and erectile dysfunction and improve quality of life. The primary question addressed in the posted results is narrower: it concerns change in urinary symptom score. Erectile function and other symptom measures appear among the secondary outcomes, but they are not interchangeable with the primary IPSS outcome.

The tamsulosin arm adds another active-treatment group, but the principal posted analysis and the recalculated comparison discussed for the primary outcome concern tadalafil versus placebo. The registry record does not report a primary comparison of tadalafil directly with tamsulosin. The result therefore describes the randomized groups and endpoint recorded, rather than answering every possible comparison between treatments.

3. Trial Design

This was a phase 3, randomized, double-blind, placebo-controlled, parallel-design, multicenter study. The registry lists triple masking. Enrollment was 909, and the study status is completed. The listed study start was 2013-09 and primary completion was 2015-12. These dates describe the registry record and do not supply further detail about the conduct or timing of individual trial procedures.

Participants were assigned to placebo, tadalafil 5 mg, or tamsulosin 0.2 mg. Tadalafil and tamsulosin were given once daily by mouth for 12 weeks during the double-blind treatment period. Their arm descriptions also specify a 4-week single-blind placebo run-in. The placebo arm description specifies matching placebo once daily for 16 weeks. The posted primary endpoint is change from baseline to Week 12, so the outcome comparison concerns the treatment period’s Week 12 assessment.

The primary outcome was a continuous measure: change in total IPSS. The registry reports least-squares mean changes and standard errors for the outcome population. That population required randomization, at least one study-drug dose, a baseline IPSS measurement, and at least one post-baseline IPSS measurement. This is not necessarily identical to every participant enrolled or randomized.

The registry describes a mixed model for repeated measures, with treatment, country or region, prior alpha-blocker therapy, baseline erectile dysfunction severity, visit, treatment-by-visit interaction, centered baseline value, placebo lead-in IPSS change, and centered baseline-by-treatment included in the model description. The centered baseline-by-treatment and treatment-by-country interactions were removed if p >= 0.10. Other details of the trial’s original design assumptions, including its sample-size justification, are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IPSS 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.

Population: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 12, measured over Baseline, Week 12.

The primary endpoint is change from baseline in total International Prostate Symptom Score (IPSS) at Week 12. IPSS total is the sum of Questions 1 through 7. Each question is scored from 0, meaning none or no symptoms, to 5, meaning frequent symptoms; the total score ranges from 0 to 35 points. Higher numerical scores indicate more severe symptoms. A negative change therefore represents a reduction in score from baseline.

IPSS is used to quantify urinary symptom severity in men with signs and symptoms of BPH. It provides a consistent numerical outcome for comparing change between randomized groups. The endpoint is not a direct measure of every aspect of BPH, erectile function, or quality of life; the registry lists separate outcomes for erectile function, sexual encounter responses, IPSS subscales, uroflowmetry measures, and postvoid residual volume.

The posted primary result is a least-squares mean change estimated with a mixed model for repeated measures. Such an adjusted model uses the repeated outcome information and the listed covariates to estimate group means. Its adjusted estimate is distinct from a simple difference calculated from the posted group means. The model’s detailed missing-data assumptions are not reported in the registry record.

Interpretation should focus on the Week 12 change and the comparison between randomized groups, rather than on the within-group changes alone. Improvement within a group does not by itself establish a treatment contrast, because the placebo group also had a mean change. The relevant comparison asks how much the estimated change differed between groups.

7. Results Posted in the Registry

• 5 mg Tadalafil: mean -5.49 versus -4.08 on control; difference -1.41 (95% CI -2.51 to -0.31), standardized effect d = -0.19; z-test p = 0.012.
• 0.2 mg Tamsulosin: mean -4.92 versus -4.08 on control; difference -0.84 (95% CI -2.09 to 0.41), standardized effect d = -0.12; z-test p = 0.187.

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 International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at Week 12

• 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:
  • 5 mg Tadalafil: mean 5.24 versus 1.88 on control; difference 3.36 (95% CI 2.13 to 4.59), standardized effect d = 0.41; z-test p = <0.001.
  • 0.2 mg Tamsulosin: mean 2.64 versus 1.88 on control; difference 0.76 (95% CI -0.64 to 2.16), standardized effect d = 0.09; z-test p = 0.287.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 5 mg Tadalafil than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 0.2 mg Tamsulosin and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Yes Responses to Question 2 of the Sexual Encounter Profile (SEP) Questionnaire at Week 12

• 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:
  • 5 mg Tadalafil: mean 23.87 versus 10.90 on control; difference 12.97 (95% CI 5.81 to 20.13), standardized effect d = 0.27; z-test p = <0.001.
  • 0.2 mg Tamsulosin: mean 6.84 versus 10.90 on control; difference -4.06 (95% CI -11.97 to 3.85), standardized effect d = -0.09; z-test p = 0.315.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 5 mg Tadalafil than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 0.2 mg Tamsulosin and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Yes Responses to Question 3 of the SEP Questionnaire at Week 12

• 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:
  • 5 mg Tadalafil: mean 36.62 versus 15.96 on control; difference 20.66 (95% CI 12.41 to 28.91), standardized effect d = 0.37; z-test p = <0.001.
  • 0.2 mg Tamsulosin: mean 17.42 versus 15.96 on control; difference 1.46 (95% CI -7.68 to 10.60), standardized effect d = 0.03; z-test p = 0.754.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 5 mg Tadalafil than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 0.2 mg Tamsulosin and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover erectile function, sexual encounter responses, IPSS, uroflowmetry, postvoid residual volume, and IPSS storage and voiding subscores. For the three continuous outcomes with detailed arm results and recalculated comparisons, the tadalafil group’s estimated changes were more positive than placebo for erectile function and the two SEP response measures. The recalculated tadalafil-versus-placebo intervals for those comparisons exclude zero. The tamsulosin comparisons on those same outcomes have intervals that include zero.

This broad pattern is consistent with the different domains measured: the primary endpoint concerns urinary symptom severity, while some secondary outcomes concern erectile function or sexual encounter responses. Those measures add context, but they do not replace the primary IPSS comparison. The full set of secondary outcomes is broader than the subset with detailed estimates used for these comparisons; outcome-specific results should be interpreted from their own reported estimates.

The registry lists 21 posted secondary outcomes. With many outcomes and group comparisons, some apparently notable results can occur by chance even when there is no true effect. The recalculated secondary p-values are unadjusted and the registry record does not report a multiplicity adjustment for these results. They therefore carry less confirmatory weight than a prespecified primary analysis, especially when considered as a group.

Secondary findings are best treated as supportive or exploratory unless the registry identifies a testing strategy that controls the chance of false-positive conclusions across outcomes. Such a strategy is not reported in the registry record. The pattern can help describe what was measured, but it cannot by itself establish broad effects across all urinary, sexual, or quality-of-life domains.

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

• Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at Week 12
• Change From Baseline in Yes Responses to Question 2 of the Sexual Encounter Profile (SEP) Questionnaire at Week 12
• Change From Baseline in Yes Responses to Question 3 of the SEP Questionnaire at Week 12
• Change From Baseline in IPSS at Week 12
• Change From Baseline in Uroflowmetry Measures at Week 12
• Change From Baseline in Postvoid Residual Volume (PVR) at Week 12
• Change From Baseline in IPSS Storage (Irritative) Subscore at Week 12
• Change From Baseline in IPSS Voiding (Obstructive) Subscore at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score whose mean change is compared between randomized groups. The registry reports least-squares mean changes and their standard errors. A standard error describes the uncertainty in an estimated mean, rather than the spread of individual participant scores. The primary model is described as a mixed model for repeated measures (MMRM), with multiple visit measurements represented in the analysis.

What does the adjusted model do?

In general, an adjusted model estimates group outcomes while accounting for specified factors. The registry’s model description includes treatment, country or region, prior alpha-blocker therapy, baseline erectile dysfunction severity, visit, and treatment-by-visit interaction. It also includes centered baseline IPSS, placebo lead-in total IPSS change, and a centered baseline-by-treatment interaction. Centering a baseline value means expressing it relative to the overall baseline mean, as the registry describes. The centered baseline-by-treatment and treatment-by-country interactions were removed if p >= 0.10.

The registry reports the model used for the least-squares mean changes, but does not report every detail needed to reproduce the analysis. For example, the specific method and p-value for the separately reported primary contrast are not reported in the registry record. The recalculated comparisons use the posted group means and standard errors and are unadjusted; they do not reproduce the mixed model.

Why distinguish an estimate from its uncertainty?

A mean difference gives the estimated direction and magnitude of a group contrast on the outcome’s scale. A confidence interval describes a range of values compatible with the observed data and the analysis assumptions. If an interval includes zero, the data are compatible with no difference as well as with values on either side of zero. If it excludes zero, that is evidence against a zero difference under the calculation used, but it does not establish clinical importance.

A p-value measures how inconsistent the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor a measure of effect size. The recalculated p-values are unadjusted. They do not account for the many outcomes or comparisons in the registry, and they are not reported as the sponsor’s model-based p-values.

Why can standard errors support a recalculation?

For a mean, its standard error indicates how precisely that mean is estimated. The posted group means and standard errors can be used for a simple, unadjusted comparison. The recalculated uncertainty uses an approximate pooled standard deviation derived from the reported summaries. That approximation does not retain the model’s covariate adjustment or repeated-measures structure. It is a supplemental way to describe the posted summaries, not a replacement for the trial’s analysis.

In general, over-dispersion occurs when outcome variability is greater than a model assumes. If ignored, uncertainty estimates can be too small and statistical evidence can appear stronger than warranted. The registry record does not report that over-dispersion was assessed or found for these continuous outcomes; this general concern should not be mistaken for a finding about this trial.

What does the comparison of changes mean?

A within-group change compares follow-up with baseline among participants in that group. A between-group difference in change compares those changes across groups. The placebo group’s change matters because improvement over time can occur in the comparison group as well. The estimated contrast, rather than the active group’s change alone, is the relevant quantity for assessing the randomized comparison.

Randomization supports comparison between groups, while masking can reduce some influences on participant reporting and outcome assessment. The registry identifies the study as randomized and triple-masked, but does not state which roles were masked. It also does not report enough detail to assess adherence, protocol deviations, or the handling of all missing observations from the registry record alone.

The model’s repeated-measures structure is intended to use outcome observations across visits, but the registry record does not state the missing-at-random assumption or other missing-data assumptions. Therefore, the model description should not be taken as a complete account of how missing outcomes may affect inference. The outcome population itself is defined by having baseline and at least one post-baseline IPSS measurement, so it is not simply an all-enrolled population.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an estimated group difference. The registry’s own primary comparison reports a mean difference of -1.41 and a 95% confidence interval from -2.25 to -0.57. The interval lies below zero, corresponding to a greater reduction in IPSS for tadalafil than placebo on the score-change scale. The width of an interval reflects both the amount of information and the variability of the outcome, along with the analysis method.

The unadjusted recalculation also estimates a mean difference of -1.41, but its 95% confidence interval is from -2.515 to -0.305. This is a summary-statistic recalculation, not the registry’s reported sponsor interval. The different interval limits illustrate that uncertainty depends on the analysis used, not only on the point estimate. The sponsor’s analysis method is not reported in the registry record, so the reason for the interval difference cannot be established from the record alone.

For the tamsulosin comparison, the unadjusted recalculated interval ranges from -2.087 to 0.407 and includes zero. That interval is compatible with a range of possible group differences, including no difference. It does not prove that the groups are equal, nor does it identify the probability that any particular value is correct.

Confidence intervals describe statistical uncertainty, not the range of individual responses. The standard errors listed with group means likewise describe the precision of estimated means and should not be confused with participant-to-participant variability. The registry does not report a minimal clinically important difference for IPSS, so the intervals cannot be used to determine whether every plausible effect is clinically important.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm for comparisons of continuous outcomes; they are not total events. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as a reference and considers detecting 100%, 75%, or 50% of that observed effect. These are planning assumptions for the illustration; the trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm under which a study would have an 80% probability of detecting the stated effect, if the assumptions used for that calculation hold. The 90% power column expresses the same idea at a higher probability of detection. Neither column is a guarantee that a future study will find an effect, and neither is a measure of the probability that the treatment effect is real.

Rows describing a smaller fraction of the observed effect require more participants per arm in these illustrations. For example, planning for 75% or 50% of the observed effect gives larger participant requirements than planning for the full observed effect. This reflects a general statistical principle: smaller differences are harder to distinguish from random variation when other assumptions are held fixed.

These are planning illustrations, not observed power for this completed trial. They do not show that the trial was adequately or inadequately powered under its own design, because the original design assumptions are not reported in the registry record.

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 = -1.410; pooled standard deviation σ = 7.455.
2. n = 2 × (1.96 + 0.842)² × 7.455² / -1.410² = 438.8, rounded up to 439 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 <- -1.41                      # observed difference in means
sigma <- 7.45452935621265                     # 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(1937871)
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 = 439 (80% power), 588 (90% power)
 75% of observed effect: n per arm = 781 (80% power), 1,045 (90% power)
 50% of observed effect: n per arm = 1,756 (80% power), 2,350 (90% power)
power.t.test: 439.7 
Simulated power at n = 439 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 a sponsor analysis for the primary tadalafil-versus-placebo comparison: a mean difference of -1.41, with a 95% confidence interval from -2.25 to -0.57. The comparison is labeled as a mean difference in final values. The registry does not give a method or p-value for this reported contrast.

The recalculated unadjusted comparison from posted summary statistics also estimates a mean difference of -1.41, with a 95% confidence interval from -2.515 to -0.305 and p = 0.012. It is a simple recalculation, not a reproduction of the sponsor’s analysis. The registry’s primary outcome means are described as least-squares means from an MMRM, while the reported contrast is separately labeled as a difference in final values. The record does not clarify how the reported contrast was calculated.

The estimates have the same direction and point estimate, but their confidence interval limits differ. Since the recalculation relies on summary statistics and an approximate standard deviation, and does not implement the trial’s full model, the two intervals should not be treated as interchangeable. The sponsor’s reported analysis is the registry’s own analysis; the recalculation is supplementary context rather than a correction or replacement.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and 2 analyses. The primary endpoint is specified as change in total IPSS at Week 12, and the registry lists multiple secondary outcomes. Testing multiple outcomes or contrasts raises a multiplicity issue: the more statistical tests considered, the greater the opportunity for at least one apparently positive result to arise by chance. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for interpreting the family of secondary outcomes.

The recalculated p-values are unadjusted, so they should be read as individual-comparison summaries rather than as evidence adjusted for all outcomes. The registry’s sponsor comparison does not include a p-value. The registry record does not report whether interim analyses were planned or conducted, or whether any other multiplicity procedures were used.

The primary outcome population consisted of randomized participants who received at least one dose, had a baseline IPSS measurement, and had at least one post-baseline IPSS measurement. This is the population definition stated for the primary analysis. It is not a complete account of all randomized participants, and it does not establish that all participants with missing follow-up measurements were included in the model.

The MMRM description identifies repeated measurements and covariates, but the registry record does not report its missing-data assumptions, the method used for any missing outcomes, or sensitivity analyses evaluating alternative assumptions. Missing observations can affect estimates if their occurrence is related to outcomes or treatment in ways not addressed by the analysis. No particular pattern or impact of missing data can be inferred from the information recorded.

These reporting gaps limit independent assessment of how robust the results are to multiplicity and missingness. They do not show that the trial’s analysis was necessarily inappropriate; they mean that these details are not reported in the registry record.

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: melanosis coli (0.5%), colon adenoma (0.5%), colorectal cancer (0.5%), acute myocardial infarction (0.3%), inguinal hernia (0.3%).

The registry reports serious adverse events among participants at risk in each group: 5 of 361 in placebo, 7 of 362 in tadalafil 5 mg, and 2 of 185 in tamsulosin 0.2 mg. It also reports other adverse events affecting 62 of 361 in placebo, 64 of 362 in tadalafil, and 21 of 185 in tamsulosin. These are event-affect counts and their stated at-risk denominators, not estimates of a causal treatment effect.

The listed serious adverse event terms include melanosis coli, colon adenoma, and colorectal cancer, each reported as 0.5%; acute myocardial infarction, inguinal hernia, and rectal polyp, each reported as 0.3%. These terms are the most frequent serious-event terms listed in the registry record, not a complete account of every safety event or a comparison of event risk between groups.

Deaths are not reported in the registry record. Differences in counts alone do not establish that treatment caused or prevented an event. The record does not provide enough information to assess event timing, exposure-adjusted rates, or detailed seriousness and relatedness judgments.

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

The primary result describes average change in urinary symptom score over the Week 12 assessment. The registry’s reported tadalafil-versus-placebo estimate is -1.41, with a 95% confidence interval from -2.25 to -0.57. The direction indicates a larger reduction in IPSS in the tadalafil group than in the placebo group under the reported comparison. The unadjusted recalculation points in the same direction, while using a different interval based on posted summary statistics.

This is evidence about a group-level score difference in the study population and period, not a guarantee of an individual response. A mean change does not show the range of responses or the proportion of participants who experienced a particular degree of change. The registry record does not report a threshold for clinical importance, so statistical evidence for a difference cannot on its own determine how important that difference is in practice.

The result does not establish effects beyond the Week 12 outcome, or effects in populations not described by the trial. The primary endpoint measures IPSS, not all symptoms, erectile function, quality of life, or safety. Those domains have separate measures in the registry, and their results require separate interpretation.

The comparison with placebo is not a direct comparison between tadalafil and tamsulosin. The tamsulosin-versus-placebo recalculation is a separate contrast and has an interval including zero. Neither comparison establishes equivalence between treatments. The trial’s results also do not by themselves determine an individual’s treatment choice; that is outside what a statistical comparison can answer.

Finally, the reported model and recalculation should not be conflated. The former is the registry’s own analysis, while the latter is an unadjusted calculation from summary statistics. The record does not provide the sponsor comparison’s method or p-value, nor all details about missing-data assumptions and multiplicity. These limits qualify how fully the reported evidence can be independently assessed.

18. Why This Trial Matters Statistically

This trial illustrates why a randomized group comparison is more informative than looking only at change within an active-treatment group. The placebo group also had a negative mean change in IPSS. The relevant primary question is therefore how the estimated changes differ between groups, not whether the tadalafil group changed from baseline in isolation.

It also illustrates the distinction between an adjusted model-based result and a summary-statistic recalculation. The registry’s least-squares means come from an MMRM with listed covariates and repeated visits. The simple recalculation uses posted means and standard errors, giving readers a supplementary comparison but not reproducing the model. The point estimate is the same in the primary comparison, while the reported interval limits differ. That distinction matters when interpreting precision.

The trial also shows why the primary outcome should be kept separate from numerous secondary outcomes. IPSS, erectile function, sexual encounter responses, and other measures address related but distinct domains. A broad set of outcomes may add descriptive context, but unadjusted testing across many outcomes warrants caution.

Finally, sample-size illustrations based on observed effects are not the same as a trial’s original design calculation or its observed power. Planning for smaller effects requires more participants under the stated illustration assumptions. The record’s missing original design assumptions, multiplicity details, and missing-data assumptions constrain what can be concluded about the design and robustness of the analysis.

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 registry record does not report a method or p-value for the sponsor’s primary contrast, and it does not explain why the reported confidence interval differs from the interval obtained by an unadjusted recalculation. The recalculation is based on posted summary statistics and an approximate standard deviation, so it cannot account for all features of the repeated-measures model.

The registry does not report the trial’s original sample-size assumptions or its sample-size justification. The planning illustration based on observed effects therefore cannot establish whether the trial was planned to detect a particular clinically meaningful difference. A minimal clinically important difference for IPSS is also not reported in the registry record.

Although multiple secondary outcomes are listed, the registry record does not describe a multiplicity strategy or the testing hierarchy. This limits interpretation of unadjusted secondary results considered collectively. The registry also does not report missing-data assumptions or sensitivity analyses for the primary MMRM. The defined primary outcome population requires at least one post-baseline measurement, which means the record’s population description should not be confused with an analysis of every enrolled participant.

The primary endpoint concerns Week 12 change in IPSS, and the record does not establish longer-term effects. Nor does the primary endpoint capture all relevant domains. The safety information includes event-affect counts and selected serious event terms, but deaths are not reported in the registry record, and detailed timing and relatedness information are not included in the registry record described.

These are limits on what can be inferred from the registry record, not proof that unreported analyses or procedures were absent. They identify where the posted information does not support a more complete assessment.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Tadalafil in Men With Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED) — NCT01937871.
• Registry record last updated 2017-06-20; status last verified 2017-05.
• Results first posted 2017-02-07.
• 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

NCT01937871 is a completed phase 3, randomized, triple-masked, parallel-design, multicenter study of tadalafil in men with benign prostatic hyperplasia and erectile dysfunction. It enrolled 909 participants and included placebo, tadalafil 5 mg, and tamsulosin 0.2 mg groups. The primary outcome was change in total IPSS at Week 12.

The registry’s sponsor analysis reports a tadalafil-versus-placebo mean difference of -1.41, with a 95% confidence interval from -2.25 to -0.57. A simple unadjusted recalculation from posted summary statistics gives the same estimate with a different interval. The record also lists secondary outcomes and adverse-event counts. Details of the original sample-size justification, multiplicity strategy, and missing-data assumptions are not reported in the registry record.