A Study Evaluating the Effect of Botulinum Toxin Type A on Semen Quality in Patients With Benign Prostatic Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating the Effect of Botulinum Toxin Type A on Semen Quality in Patients With Benign Prostatic Hyperplasia (NCT00894517), a randomized phase 1, phase 2 study. The primary outcome is Percent Change in Total Sperm Count Per Ejaculate.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group Phase 1/Phase 2 study. Its masking classification is quadruple; the record does not specify which study roles were masked. The trial was completed, with enrollment of 61. The listed start was 2009-08 and the primary completion date was 2012-06. The brief description says that the study evaluated effects on semen quality over 24 week in patients with signs and symptoms of benign prostatic hyperplasia.

Participants were assigned to botulinum toxin type A or placebo (normal saline). The active arm received onabotulinumtoxinA 200U injected into the prostate on Day 1, while the placebo arm received saline injected into the prostate on Day 1. The outcome population is described as the safety population, comprising randomized participants who received treatment. The primary endpoint results list 29 participants in the active arm and 30 in the placebo arm. The registry does not report additional details about allocation procedures, concealment, masking roles, or participant flow.

The primary outcome was percent change in total sperm count per ejaculate, measured from baseline to Week 12. Four secondary outcome names are listed: change from baseline in log transformed sperm concentration, ejaculatory volume, total sperm motility, and normal sperm morphology. Although those outcome names appear in the registry, numerical results for them are not reported in the registry record. The registry's original sample-size justification, planned analysis details, interim analyses, and reasons for the recorded enrollment 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

Analysis population for the primary outcome, as defined in the registry: Safety population included all randomized participants who received treatment.

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 Percent Change in Total Sperm Count Per Ejaculate, measured over Baseline, Week 12.

The primary endpoint is percent change in total sperm count per ejaculate from baseline to Week 12. It combines information about ejaculatory volume and sperm concentration to describe the total sperm count in an ejaculate. The registry defines a positive percent change from baseline as improvement; that definition describes the direction of the measure, not the certainty or clinical importance of an observed change.

Each measurement was based on the average of two semen samples collected 2 to 5 days apart at baseline and again at Week 12. Using repeated samples at each assessment can reduce dependence on the result of a single sample, which may vary. This is a general measurement consideration; the registry does not report the extent to which repeated samples reduced variability in this trial.

Total sperm count per ejaculate was selected as the primary outcome within a study evaluating semen quality in patients with benign prostatic hyperplasia. A continuous endpoint preserves the magnitude and direction of change rather than classifying participants only as improved or not improved. The reported arm values are means, with standard deviations of 56.77 for botulinum toxin type A and 57.56 for placebo. Those spreads describe variability among participants and help explain why a difference between group means can remain uncertain even when the means are not identical.

The registry does not report a threshold for a clinically important change. The endpoint therefore describes measured change, but the record alone does not establish what size of change would be meaningful to patients or clinicians.

7. Results Posted in the Registry

• Botulinum Toxin Type A: mean 3.62 versus -12.22 on control; difference 15.84 (95% CI -13.34 to 45.02), standardized effect d = 0.28; z-test p = 0.287.

8. Statistical Interpretation

9. Statistical Methods Explained

The main outcome is continuous: each participant has a percent change in total sperm count per ejaculate, and the registry summarizes each arm using a mean. For a continuous measure, a group mean represents the central average, while a standard deviation describes how dispersed individual measurements are around that mean. These quantities answer different questions. A mean describes the group’s average result; a standard deviation describes participant-level variability.

What does the mean difference represent?

The reported mean difference is 15.84 for botulinum toxin type A relative to placebo. It expresses the contrast between the two arm means on the endpoint’s percent-change scale. It is not a percentage-point change in the number of sperm, nor is it the average change for an individual participant. The arm means are 3.62 and -12.22. Because the reported contrast is a difference in means, its interpretation is about average change between groups, not whether every participant changed in the same direction.

A treatment comparison is generally more informative than looking at change in one arm alone because change can occur over time for reasons unrelated to the intervention. Randomization is intended to make groups comparable on average at the start of a trial, subject to chance variation and the details of how randomization was implemented. The registry identifies the study as randomized, but its allocation procedures and baseline balance are not reported in the registry record. No baseline-adjusted model or other adjustment is described.

How should the p-value be read?

The unadjusted p-value is 0.287. In general, a p-value measures compatibility between observed data and a null hypothesis under the assumptions of a particular statistical model. It is not a measure of effect size, and it does not state the probability that a treatment has no effect. A value such as this should be considered alongside the estimated difference and its interval. The registry does not report the test used to calculate the p-value, its distributional assumptions, or a prespecified significance threshold for the primary analysis. The significance level of 0.05 appears among the assumptions for a separate sample-size planning illustration, not as a reported original analysis plan.

What does an interval add?

The reported interval for the mean difference extends from -13.34 to 45.02. In general, a confidence interval presents a range of effect estimates compatible with the data and the method used to construct it. Narrower intervals indicate greater precision, while wider intervals indicate less precision. The interval in this study contains zero, meaning that no difference is among the values compatible with the reported range. It also includes positive and negative values, so the direction and size of the underlying difference remain uncertain. The confidence level and interval construction method are not reported in the registry record, and the interval should not be assigned an unstated confidence percentage.

Why do sample size and variability matter?

Precision depends on the amount of information in the data and on variability. In general, more participants can improve precision, while greater outcome variability can make an estimate less precise. The standard deviations are 56.77 for botulinum toxin type A and 57.56 for placebo; these reflect substantial dispersion on the endpoint scale. The endpoint groups contain 29 and 30 participants. The observed comparison therefore needs to be read in light of both the between-group estimate and the considerable spread within groups.

The posted sample-size illustration uses the observed effect and specified planning assumptions to show how many participants per arm would be needed for different target power levels under hypothetical designs. Such planning calculations are not a report of the trial’s original design rationale. The original sample-size justification and assumptions are not reported in the registry record. The planning illustration also does not show the probability that this completed study detected an effect; that would be an observed-power interpretation and is not appropriate.

What analysis details are absent?

The registry describes the primary population as randomized participants who received treatment, but it does not specify how missing measurements were handled, whether any endpoint data were excluded, or whether analysis used all available observations. The model, treatment of baseline values, transformations, covariates, and diagnostics are not reported in the registry record. There is also no reported interim-analysis plan, adjustment for multiple outcomes, or sensitivity analysis. These omissions limit how fully the numerical comparison can be reconstructed or assessed.

The record names four secondary outcomes, but numerical results for those measures are not reported. With multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately; methods for addressing that issue depend on a prespecified analysis plan. No such plan is reported. This general consideration does not imply that any unreported secondary result was significant or non-significant.

10. Confidence Intervals and Precision

The estimated mean difference in percent change is 15.84, and the reported interval runs from -13.34 to 45.02. The interval is wide enough to include zero and effects on both sides of zero. That means the point estimate alone gives an incomplete picture: uncertainty around the estimate includes no mean difference and a range of possible differences. The registry does not state the confidence level or construction method for this interval, so neither should be assumed.

In general, an interval conveys precision rather than certainty about a single true value. A narrow interval would indicate that the data distinguish among fewer plausible values, while a wide interval leaves more possibilities open. Here, the range cautions against treating 15.84 as a precise estimate of the underlying contrast. It also cautions against interpreting the inclusion of zero as proof that the treatments have identical effects. Absence of a clearly distinguished difference and evidence of equivalence are not the same conclusion; equivalence requires a specified margin and an analysis designed to assess it. Neither an equivalence margin nor an equivalence analysis is reported in the registry record.

The arm standard deviations are 56.77 for botulinum toxin type A and 57.56 for placebo, with 29 and 30 participants in the endpoint groups. In general, variation among individual measurements and the amount of data both affect the precision of a group comparison. The outcome is based on averaged samples at baseline and Week 12, but the registry does not report the reliability of those measurements or how missing samples affected precision.

The interval and unadjusted p-value of 0.287 are consistent with an uncertain comparison. No clinical-importance threshold is reported, so the interval cannot be used to decide whether its possible effects would be meaningful in practice. Statistical precision and clinical importance are related questions, but they are not interchangeable.

11. Planning a Similar Trial: Sample Size

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

The sample-size illustration gives hypothetical planning requirements in participants per arm for a two-group comparison. It is not a report of the trial’s original target or its original design justification, which are not reported in the registry record. The assumptions listed for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. For this continuous outcome, the displayed counts refer to participants per arm; the alternative convention of total number of events applies to time-to-event illustrations, not this comparison.

The 80% power column describes the planned sample size per arm under which the assumed design would have an 80% chance of detecting the specified effect at the stated significance level, if the assumptions hold. The 90% column uses a higher target chance of detecting that same specified effect. These are design probabilities under hypothetical assumptions, not probabilities that the result is true or that a treatment is effective.

The rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects need more participants to distinguish them from random variation under the same general planning assumptions, so the requirements rise as the assumed effect becomes smaller. The count for planning at 100% of the observed effect is not a recommendation: it relies on an effect estimated from this study, and an observed estimate may not represent the effect in a future study.

This is not observed power. It is a planning illustration based on the observed effect and stated assumptions. The registry record does not report whether the original study was designed using these assumptions or a different sample-size approach.

12. 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 = 15.840; pooled standard deviation σ = 57.177.
2. n = 2 × (1.96 + 0.842)² × 57.177² / 15.840² = 204.5, rounded up to 205 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 <- 15.84                      # observed difference in means
sigma <- 57.1768060563636                     # 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(894517)
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 = 205 (80% power), 274 (90% power)
 75% of observed effect: n per arm = 364 (80% power), 487 (90% power)
 50% of observed effect: n per arm = 819 (80% power), 1,096 (90% power)
power.t.test: 205.5 
Simulated power at n = 205 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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and four secondary outcome names. Those secondary measures are change from baseline in log transformed sperm concentration, ejaculatory volume, total sperm motility, and normal sperm morphology. Numerical results for the secondary outcomes are not reported in the registry record. The record does not report how many hypotheses were intended for formal testing, whether a hierarchy was specified, or whether any multiplicity adjustment was planned. When multiple outcomes are tested, general statistical practice may use prespecified methods to control the interpretation of chance findings. Without the original plan, it is not possible to determine how the listed outcomes were intended to be interpreted together.

Missing-data methods are also not reported. The primary outcome population is described as the safety population, including randomized participants who received treatment. The record does not explain how participants without endpoint measurements were handled, whether all measurements were included, or how missing values were addressed. It does not describe exclusions, imputation, or sensitivity analyses. As a result, the degree to which the endpoint comparison depends on complete observations cannot be assessed from the registry record alone.

The registry reports arm-level endpoint values and an unadjusted comparison summary but does not describe the statistical model or test, baseline adjustment, covariates, or analysis diagnostics. The count of formal analysis entries is zero; further analysis details are not reported in the registry record. No interim analysis plan is reported. The original sample-size rationale, protocol-level significance threshold for the primary comparison, and prespecified analysis plan are not reported either.

These gaps do not by themselves show that an analysis was inappropriate. They limit the ability to distinguish prespecified decisions from choices made after data collection, and to assess whether the posted comparison reflects all randomized participants or a subset. The endpoint population definition is useful, but it does not resolve those unanswered questions.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (3.3%), coronary artery occlusion (3.3%), cholecystitis acute (3.3%), sepsis (3.3%), convulsion (3.3%).

The registry reports serious adverse events for 0 of 29 participants in the botulinum toxin type A group and 3 of 30 participants in the placebo group. These are counts of participants reported as affected, not rates calculated from person-time. The record does not provide event timing, duration, severity details beyond the serious classification, or an assessment of causality for the individual events. Serious adverse event counts should therefore be read as descriptive safety information, not as a stand-alone comparison establishing a treatment-related difference.

The registry lists Acute myocardial infarction, Coronary artery occlusion, Cholecystitis acute, Sepsis, Convulsion, and Acute respiratory failure among the serious adverse event terms, each with a reported value of 3.3%. The record does not make clear in this listing which arm each term belongs to, or whether a participant could contribute more than one term. Those percentages should not be used to infer group-specific risks without that information. Death counts are not reported in the registry record; a missing count should not be interpreted as zero.

Other adverse events are reported for 18 of 29 participants in the active arm and 12 of 30 in the placebo arm. These are separate from the serious adverse event counts and should not be combined with them. The registry does not provide enough information to assess event attribution or compare safety profiles in detail.

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

The primary result is a comparison of mean percent change in total sperm count per ejaculate between participants who received botulinum toxin type A and participants who received saline. The reported mean difference is 15.84, with an interval from -13.34 to 45.02 and an unadjusted p-value of 0.287. Together, these statistics describe an uncertain estimate: the interval includes zero and permits values favoring either group. The result does not establish a precise difference.

At the same time, this result does not demonstrate equivalence. A non-significant unadjusted comparison is not evidence that the groups are identical, particularly when the estimate is imprecise. A conclusion of equivalence would require a defined margin and a suitable analysis, neither of which is reported in the registry record. The record also does not report a threshold for a clinically important change, so it cannot show whether a particular value within the interval would matter to patients.

The endpoint is a measure of semen quality defined through total sperm count per ejaculate. A positive change was designated as improvement, but that direction label does not establish the practical meaning of the size of change. The registry does not provide numerical results for the four named secondary outcomes, so they cannot be used to broaden or qualify the primary result.

Safety counts are descriptive. The registry reports serious adverse events affecting 0 of 29 active-arm participants and 3 of 30 placebo-arm participants, but it does not provide sufficient event-level details or causal assessments to attribute those events to study treatment. Missing death counts cannot be treated as zero.

Overall, the posted primary outcome data give an estimate and uncertainty range for one comparison in this completed randomized study. They do not settle whether the intervention changes semen quality, establish clinical importance, show equivalence, or support conclusions about outcomes not numerically reported. Interpretation is also limited by absent details on missing data, the analysis plan, and the original sample-size rationale.

16. Why This Trial Matters Statistically

This study raises a useful statistical distinction between an estimated effect and the precision of that estimate. The reported mean difference is 15.84, but the interval from -13.34 to 45.02 includes zero and a broad range of possible values. Reporting the point estimate alone could make the comparison seem more definite than the data support. Reading the estimate with its interval makes the uncertainty visible.

The continuous endpoint also illustrates why variability matters. The standard deviations are 56.77 and 57.56, compared with endpoint group sizes of 29 and 30. In general, when individual measurements vary substantially, group means can be estimated less precisely unless there is sufficient information to narrow the uncertainty. This trial’s outcome measurement averaged two semen samples at each time point, a design detail relevant to how the measure was obtained, though the record does not quantify its effect on precision.

Another important lesson is that a p-value does not answer every substantive question. The unadjusted value of 0.287 does not show that the groups are equivalent, and it does not say whether any possible effect is clinically important. The registry does not report an equivalence margin, a clinical-importance threshold, or a multiplicity plan for the primary and secondary outcomes. Those absences matter when translating a statistical comparison into a broader interpretation.

Finally, registry results are easier to assess when analysis plans, participant flow, missing-data handling, and secondary outcome results are available. Here, numerical results for the named secondary outcomes and details of the original statistical plan are not reported in the registry record. This limits the ability to reconstruct how the posted comparison fits the full planned analysis. The trial therefore offers a focused example of how results can be numerically informative while still leaving important uncertainty about analysis and interpretation.

17. 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 trial-specific limitations constrain interpretation. The registry identifies the endpoint population as randomized participants who received treatment, but it does not explain participant flow or how missing Week 12 outcomes were handled. Enrollment is recorded as 61, while primary endpoint results list 29 participants in the botulinum toxin type A arm and 30 in the placebo arm. The record does not explain the relation between those counts, so no conclusion about exclusions, non-treatment, or missing outcomes can be drawn.

The primary measure relies on semen samples collected at baseline and Week 12. The registry says that an average of two samples collected 2 to 5 days apart was used at each assessment, but does not report sample completeness, measurement reliability, or whether all scheduled samples were available. It also does not report the method used to analyze percent change or whether baseline values were included in a model.

The interval method and confidence level are not reported in the registry record. Details of the statistical test, model assumptions, covariate adjustment, and diagnostic checks are also absent. The original sample-size justification and any interim analyses are not reported. Thus, the planning illustration based on the observed effect should not be confused with the rationale used to set the trial’s enrollment.

Four secondary outcomes are named, but their numerical results are not reported. The record also does not specify a multiplicity strategy or a threshold for a clinically important difference. Those omissions limit assessment of the broader outcome pattern and of the practical meaning of the primary estimate.

Finally, serious adverse event terms are listed with percentages but without clear arm attribution in the term listing. Event timing and causal assessments are not reported, and death counts are absent. These details limit interpretation of safety information and prevent drawing conclusions about comparative safety from the counts alone.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study Evaluating the Effect of Botulinum Toxin Type A on Semen Quality in Patients With Benign Prostatic Hyperplasia — NCT00894517.
• Registry record last updated 2013-09-30; status last verified 2013-07.
• Results first posted 2013-09-30.
• 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.

21. Record Summary

The registry record describes a completed, randomized, quadruple-masked, parallel Phase 1/Phase 2 study of botulinum toxin type A versus placebo (normal saline) in patients with benign prostatic hyperplasia. Enrollment was 61. The active intervention was onabotulinumtoxinA 200U injected into the prostate on Day 1; placebo saline was also injected on Day 1.

The primary outcome was percent change in total sperm count per ejaculate from baseline to Week 12. The reported arm means were 3.62 for botulinum toxin type A and -12.22 for placebo; the reported mean difference was 15.84, with an interval from -13.34 to 45.02 and an unadjusted p-value of 0.287. Four secondary outcomes are listed, but numerical results for them are not reported in the registry record.

The registry does not report the original sample-size rationale, detailed analysis plan, missing-data methods, or confidence-interval method. The primary comparison is therefore best read as a descriptive estimate with substantial uncertainty, rather than a definitive statement about equivalence or clinical importance.