Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue (WATER): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue (WATER) (NCT02505919), a randomized na study. The primary outcome is Proportion of Subjects With Adverse Events (Clavien-Dindo Grading System Grade 2 or Higher or Any Grade 1 Event Resulting in Persistent Disability).

2. Clinical Question

3. Trial Design

WATER was a prospective, multicenter, randomized, double-blind, parallel-group study comparing Aquablation using the AQUABEAM System with TURP for treatment of LUTS. The registry lists BPH as the condition, identifies PROCEPT BioRobotics as the sponsor, and reports the study as completed. The recorded enrollment is 184.

The intervention arm is called Treatment in the outcome record; the active comparator arm is TURP. For the primary safety outcome, the posted denominators are 116 and 65, respectively. These arm-specific denominators should not be confused with the overall enrollment. The reason the endpoint denominators differ from one another and from the enrollment figure is not reported in the registry record.

The primary safety endpoint was assessed three months after treatment. The brief summary also says that safety and effectiveness primary endpoints were measured at three and six months, respectively, and that participants were followed out to five years for long-term clinical data. The specific effectiveness endpoint results are not included in the posted results described in this record.

The registry identifies the allocation as randomized, the masking as double, and the model as parallel. Further details about how randomization or masking was implemented are not reported in the registry record. The original sample-size justification and design assumptions are also not reported in the registry record, so planning illustrations based on the observed effect should not be read as evidence of the trial’s original design rationale.

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.

Treatment

1 Week Follow-Up

1 Month Follow-Up

3 Months Follow-Up

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 Proportion of Subjects With Adverse Events (Clavien-Dindo Grading System Grade 2 or Higher or Any Grade 1 Event Resulting in Persistent Disability), measured over Three months post-treatment.

The primary endpoint is the proportion of participants with an adverse event meeting a specified severity and attribution definition through three months after treatment. The event had to be judged probably or definitely related to the study procedure and either be classified as Clavien-Dindo Grade 2 or higher, or be a Grade 1 event resulting in persistent disability. The registry gives ejaculatory disorder and erectile dysfunction as examples of persistent disability.

The endpoint is a binary participant-level measure: a participant either meets the definition or does not. It focuses on procedure-related complications, rather than events that represent lack of effective treatment; the record explicitly distinguishes those concepts. Using a defined severity threshold can make the safety comparison more focused on events considered clinically consequential under the endpoint definition. Including persistent disability after a Grade 1 event also means that severity grade alone does not determine whether an event qualifies.

The result is expressed as a percentage of participants and is reported at the three-month assessment. The registry reports 26.0% for the AQUABEAM arm and 42.0% for TURP. These proportions describe the recorded endpoint within each arm; they do not by themselves explain the type, duration, or individual consequences of every event.

7. Results Posted in the Registry

• Treatment: 25.9% (30/116) versus 41.5% (27/65) on control; risk difference -15.7 percentage points (95% CI -30.1 to -1.3), risk ratio 0.62 (0.41–0.95); unadjusted two-proportion z-test p = 0.029.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary at the participant level: the registry records whether a participant had at least one event meeting the definition. A binary endpoint can be summarized as a proportion in each arm. The posted proportions are 26.0% for the AQUABEAM arm and 42.0% for TURP, with their respective 95% confidence intervals. This summary does not retain all detail about event timing, recurrence, or severity beyond the qualifying definition.

What does the risk difference express?

A risk difference compares the event proportions in two groups by subtracting one proportion from the other. The posted comparison is oriented as Treatment relative to the active comparator, and its estimate is -0.157. A negative value therefore corresponds to a lower observed event proportion in Treatment under that direction. The confidence interval for the risk difference is -0.301 to -0.013. It expresses uncertainty about the size of the contrast, conditional on the calculation’s statistical assumptions; it does not describe a range containing a fixed proportion of individual participant outcomes.

A risk difference is an absolute contrast, unlike a relative measure such as a risk ratio or odds ratio. Absolute contrasts can be useful for understanding the scale of an observed difference between groups. The registry also posts risk-ratio and odds-ratio estimates, but the primary interpretation uses the risk difference because it directly compares the arm-specific proportions. No adjusted comparison is reported in the registry record.

What does the p value tell the reader?

The posted unadjusted p value is 0.029. In general, a p value describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the magnitude or clinical importance of an effect. The term unadjusted indicates that this reported comparison is not presented as adjusted for other factors. The precise statistical test and any covariate model are not reported in the registry record.

The relationship between a confidence interval and a test depends on the methods used to construct each. In this record, the posted risk-difference interval does not include zero, and the unadjusted p value is 0.029. These quantities both describe uncertainty about the group contrast, but neither accounts for possible issues that are not represented in the calculation, such as missing outcomes or deviations from the planned analysis.

Why can the event counts and percentages differ in presentation?

The registry gives endpoint percentages rounded to whole numbers and reports arm denominators of 116 and 65. It also gives counts used in the comparison: 30 events among 116 participants for Treatment and 27 among 65 for the comparator. The posted comparison uses the more detailed proportions derived from these counts, so its estimate is reported with more decimal places than the rounded arm percentages. Rounding can make a displayed percentage insufficient to reproduce a contrast exactly.

For a binary endpoint, the uncertainty in a proportion depends in part on the number of observations and the frequency of the event. A confidence interval makes that sampling uncertainty visible. The comparative interval also reflects uncertainty in the difference between the two proportions. Neither interval includes uncertainty arising from unreported aspects of data collection or study conduct.

What is the role of randomization and masking?

Random allocation is intended to make groups comparable, on average, with respect to measured and unmeasured characteristics before treatment. Masking can reduce the influence of knowledge about assigned treatment on some aspects of care or outcome assessment. The registry identifies the study as randomized and double-blind, but does not describe the sequence-generation method, allocation concealment, who was masked, or how masking was maintained. Those details are not reported in the registry record, so the labels alone do not establish how these protections operated in practice.

The recalculated comparison is a simple unadjusted calculation from the posted summary statistics. It is not a substitute for a full analysis plan or participant-level analysis. The registry record lists no posted secondary analyses and no analysis records for this outcome set. It does not report whether additional statistical models, sensitivity analyses, or interim analyses were conducted. The result should therefore be read at the level of detail actually documented: arm proportions, confidence intervals, and an unadjusted group contrast.

10. Confidence Intervals and Precision

The arm-specific 95% confidence intervals communicate uncertainty in the estimated proportions. For the AQUABEAM arm, the interval is 18.2% to 34.8%; for TURP, it is 29.4% to 54.4%. In general, a confidence interval is a range produced by a statistical procedure that, under its assumptions, would cover the target value in repeated applications at the stated confidence level. It is not a guarantee that the true value lies in this particular interval, nor does it describe the range of individual participant outcomes.

The comparative estimate is a risk difference of -0.157, with a 95% confidence interval from -0.301 to -0.013. This interval describes uncertainty in the contrast rather than uncertainty in either arm’s proportion alone. It does not include zero, but its endpoints span a range of possible negative differences. That breadth matters: the point estimate alone does not convey how precisely the difference has been estimated.

The arm denominators are 116 and 65. Different denominators can lead to different levels of precision, and the interval widths also depend on the observed event proportions and the interval method. The endpoint values are presented as whole-number percentages, while the comparison is reported with greater decimal detail. The extra decimal places do not remove sampling uncertainty; the confidence interval remains essential to interpretation.

Confidence intervals do not address every source of uncertainty. They generally reflect sampling variation under their method’s assumptions, not possible selection effects, unrecorded outcome data, misclassification, or limits in generalizing beyond the participants studied. Further information about missingness and analysis populations is not reported in the registry record.

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 planning figures are participants per arm, not total event counts. They are illustrations calculated from the observed effect, rather than the trial’s original sample-size justification. The registry record does not report the trial’s original design assumptions. The planning assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 142 participants per arm for 80% power and 189 participants per arm for 90% power. For planning for 75% of the observed effect, they are 260 participants per arm for 80% power and 347 participants per arm for 90% power. For planning for 50% of the observed effect, they are 599 participants per arm for 80% power and 801 participants per arm for 90% power.

In general, power is the chance that a study will reject the specified null hypothesis if the assumed effect is the true effect and the other planning assumptions hold. The 80% and 90% columns give alternative target probabilities for detecting the stated effect under the stated assumptions; a higher target generally requires a larger planned sample. The planning curve represents this relationship between assumed effect size and the required participants per arm. Smaller effects need more participants to distinguish them from random variation with the same target power.

These calculations are planning illustrations, not observed power. They do not establish what power the completed trial had under its actual design, nor do they show that the trial was planned using these assumptions. The original sample-size justification is not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.415; treatment proportion p₁ = 0.259; average p̄ = 0.337.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6685 = 1.3102.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6592 = 0.5548.
4. n = (1.3102 + 0.5548)² / (-0.1568)² = 141.5, rounded up to 142 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
p0 <- 0.415384615384615                          # control proportion
p1 <- 0.258620689655172                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2505919)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 142 (80% power), 189 (90% power)
 75% of observed effect: n per arm = 260 (80% power), 347 (90% power)
 50% of observed effect: n per arm = 599 (80% power), 801 (90% power)
power.prop.test: 141.5 
Simulated power at n = 142 per arm: 0.807 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 record lists seven outcome measures, but reports no posted secondary outcome results in the record. It lists zero analysis records. The primary safety endpoint has a posted comparison, but the record does not provide a complete statistical analysis plan or describe how the primary endpoint related to any other planned analyses.

Multiplicity arises when several hypotheses or outcomes are tested: the more comparisons considered, the greater the chance that at least one result may appear notable by chance if no adjustment or other strategy is used. Whether a correction is needed depends on the prespecified testing hierarchy and the interpretation intended for the results. The registry record does not report a multiplicity strategy, adjustment, or hierarchy. It is therefore not possible to determine from the recorded information whether the posted unadjusted p value was part of a broader controlled testing procedure.

The endpoint denominators are 116 for Treatment and 65 for the active comparator, while recorded enrollment is 184. The registry record does not explain the difference between these figures or report the number of participants with missing endpoint data, reasons for missingness, or methods used to address it. It also does not state whether the endpoint analysis used an intention-to-treat, per-protocol, or other analysis population. These details are important because the way participants are included and missing outcomes are handled can affect estimates and their interpretation.

The record describes double masking and randomized allocation but does not report interim analyses or stopping rules. It does not describe the statistical model beyond the posted unadjusted comparison. Without these details, readers cannot assess whether additional analyses were planned, whether any data-dependent decisions were made, or how robustness to missing data and analytic choices was evaluated. The absence of these details in the registry record does not establish that such procedures were or were not used; it means they are not reported in the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bleeding (6.2%), urinary urgency/frequency/difficulty/leakage (non-procedure-related) (4.3%), cardiac (non-procedure-related) (3.4%), urinary retention (3.1%), non-urologic (2.6%).

The serious adverse event summary reports 24 affected participants among 116 at risk in the Treatment arm and 14 among 65 at risk in the active comparator arm. The corresponding counts for other adverse events are 75 among 116 and 53 among 65. Deaths are recorded as 4 and 1, respectively. These figures are separate safety summaries and should not be assumed to be mutually exclusive or directly comparable with the primary endpoint, which has a specific procedure-related severity definition and a three-month timeframe.

The most frequently listed serious adverse event terms are Bleeding at 6.2%, Urinary urgency/frequency/difficulty/leakage (non-procedure-related) at 4.3%, Cardiac (non-procedure-related) at 3.4%, Urinary retention at 3.1%, Non-urologic at 2.6%, and Other bleeding (non-procedure-related) at 1.7%. The registry record does not give the denominator or a detailed attribution rule for each listed term in this summary. These categories describe recorded events; they do not establish that treatment caused them.

Counts of affected participants are not necessarily counts of all events, since one participant may have more than one event. The registry record does not explain whether participants appear in multiple categories or supply further detail about timing and adjudication. The summaries should therefore be read as descriptive safety information, distinct from the primary endpoint comparison.

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

The posted primary safety results show a lower observed proportion meeting the endpoint definition in the AQUABEAM arm than in the TURP arm: 26.0% compared with 42.0%. The risk-difference estimate is -0.157, with a 95% confidence interval from -0.301 to -0.013. This describes the direction and uncertainty of the recorded comparison in this randomized study. It is not, on its own, a complete account of comparative safety or clinical benefit.

The endpoint includes only adverse events judged probably or definitely related to the procedure, with the specified Clavien-Dindo severity or persistent-disability criterion, and is assessed through three months. It does not cover every possible adverse event or later outcomes. The brief summary says participants were followed out to five years to collect long-term clinical data, but the long-term results are not included among the results described in the registry record.

The result does not establish that every participant in one arm had a lower risk than every participant in the other. Group proportions summarize outcomes across participants, while the confidence interval communicates uncertainty in the estimated difference. Nor does the result establish that the observed contrast is clinically important: the registry record does not provide a threshold for clinical importance or a full analysis of participant-level consequences.

Interpretation is also limited by details not reported in the registry record, including missing outcome handling, analysis populations, multiplicity procedures, and the original sample-size assumptions. The trial is randomized and double-blind according to the record, but operational details of allocation and masking are not reported. These limits do not erase the posted estimates; they define how far the estimates can be interpreted using the registry information alone.

The findings should be understood as a comparison of the registered endpoint in the analyzed groups, with the uncertainty represented by the reported intervals. They do not answer all questions about effectiveness, durability, or the overall balance of outcomes between the procedures.

16. Why This Trial Matters Statistically

This trial illustrates why a safety comparison needs a carefully defined endpoint. The primary measure is not simply any adverse event: it requires a judgment of probable or definite relation to the procedure and a specified severity or persistent-disability criterion. That definition helps clarify what the proportions represent and prevents the primary result from being conflated with broader adverse-event summaries.

It also shows why both arm estimates and the comparative estimate matter. The arm percentages describe the observed endpoint frequency within each group, while the risk difference directly expresses the contrast. The 95% confidence interval adds information about precision that a point estimate or p value alone cannot provide. Here, the interval for the risk difference is negative throughout, but it still spans a range of possible magnitudes.

Randomization and masking are important design features, but their labels do not replace reporting of implementation, participant flow, analysis populations, and missing-data methods. The registry gives arm denominators that differ from overall enrollment and from one another, without explaining why. That makes transparent reporting of who contributed outcome data especially relevant to interpretation.

Finally, planning calculations based on an observed effect are distinct from a trial’s original design. The registry does not report the original sample-size rationale, so the illustrative requirements for different effect assumptions should be read as planning scenarios rather than evidence about the study’s intended power. Together, these points help distinguish what the observed estimate says from what remains uncertain or undocumented.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record provides a concise outcome result but does not report several details needed for a fuller appraisal. It does not describe the method for random sequence generation or allocation concealment, identify who was masked, or explain how masking was maintained. Although the study is labeled randomized and double-blind, the operational procedures are not reported in the registry record.

The overall enrollment is 184, while the primary endpoint denominators are 116 and 65. The registry record does not explain participant flow, exclusions from the endpoint analysis, or the reason for the differing denominators. It also does not state how missing outcomes were handled or identify the analysis population. These omissions limit assessment of how representative the analyzed groups are of all enrolled participants.

The registry identifies seven outcome measures but does not post secondary outcome results in the record. It does not report a full statistical analysis plan, multiplicity approach, interim analyses, or stopping rules. The original sample-size justification and design assumptions are not reported. Consequently, the planning illustrations based on the observed effect cannot be used to infer the intended design or the study’s original power target.

The primary safety endpoint is limited to qualifying procedure-related events through three months. Although follow-up was planned out to five years for long-term clinical data, those results are not included in the reported information. The serious adverse event summaries also do not provide detailed event attribution, timing, or an explanation of whether participants can appear in multiple categories. These limitations affect the scope and detail of interpretation, without changing the numerical estimates recorded for the primary endpoint.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue (WATER) — NCT02505919.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2020-04-08.
• 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

WATER is a completed, prospective multicenter randomized double-blind parallel study comparing Aquablation with the AQUABEAM System against TURP for LUTS associated with BPH. The registry reports enrollment of 184 and identifies PROCEPT BioRobotics as sponsor.

The primary safety endpoint is the proportion with specified procedure-related adverse events through three months. The posted proportions are 26.0% in Treatment and 42.0% in the active comparator, with a risk difference of -0.157 and a 95% confidence interval from -0.301 to -0.013. The unadjusted p value is 0.029.

The endpoint denominators are 116 and 65. The registry record does not explain the differing denominators or report the original sample-size justification, missing-data methods, analysis populations, or multiplicity procedures. Long-term follow-up was described, but long-term results are not included in the posted outcome information.