Preemptive Local Anesthesia in Vaginal Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preemptive Local Anesthesia in Vaginal Surgery (NCT00318292), a randomized phase 4 study. The primary outcome is Visual Analogue Scale (VAS) Pain Score.

2. Clinical Question

The registry describes a prospective, randomized trial of preemptive local anesthesia in vaginal surgery. The clinical question is focused: does the group assigned to local analgesia have a different average early postoperative pain score from the group assigned to placebo? The posted primary outcome is a continuous score on a scale from 0 (None) to 10 (Worst), recorded 30 minutes post-op.

This is a comparison of group averages at a specified time, not a report of each participant’s pain experience over the whole recovery period. The record does not give more detail about eligibility criteria, the characteristics of participants, or how the outcome was collected. Those details are not reported in the registry record, so the scope of the population to which the comparison may apply cannot be described more precisely.

The trial record identifies bupivacaine and epinephrine as the active intervention and placebo as the comparator. It does not report enough detail to characterize the contents or administration of the placebo, nor does it describe the exact procedure used to deliver the local anesthetic beyond the summary description. The question answered by the posted endpoint is therefore the early average pain-score comparison between the randomized groups, rather than a broader assessment of pain, recovery, or other outcomes.

3. Trial Design

The registry classifies this as a Phase 4, randomized, parallel-group trial with quadruple masking. Enrollment was 90, with 45 participants in the preemptive local analgesia group and 45 in the placebo group. The record lists the trial as completed. It gives a start date of 2006-04 and a primary completion date of 2008-03.

In a parallel-group design, participants are assigned to one of the study arms and the groups are compared. Here, the active arm is titled Preemptive Local Analgesia (PLA), and the comparator arm is titled Placebo. The intervention listing names bupivacaine and epinephrine; the arm descriptions characterize the active and placebo assignments as preemptive local analgesia and placebo for preemptive local analgesia, respectively.

Random allocation is intended to make the groups comparable on average at the point of assignment, although it cannot guarantee that every characteristic is balanced in a trial of this size. The registry’s quadruple-masking label indicates masking at several levels, but it does not identify which specific roles were masked or explain how masking was maintained. Those details are not reported in the registry record.

The record lists one outcome measure and one reported analysis. Its primary outcome is the mean Visual Analogue Scale pain score at 30 minutes post-op. No secondary posted outcomes are listed. The trial’s original sample-size assumptions, planned analysis details beyond the reported t-test, and any interim analysis plan are not reported in the registry record. The planning illustrations elsewhere on this page are based on the observed effect and should not be read as 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.

Before assignment: 95 of the eligible patients consented to participate. 3 were excluded prior to treatment because they converted to abdominal hysterectomy. 2 were excluded because the study treatment was unintentionally missed by the operating staff.

Overall Study

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 Visual Analogue Scale (VAS) Pain Score, measured over 30 minutes post-op.

The primary endpoint is the Visual Analogue Scale (VAS) pain score at 30 minutes post-op. The score runs from 0 (None) to 10 (Worst) points. The posted summaries report the mean and standard deviation for each group, making this a continuous outcome: each participant contributes a score, and the group summary describes its average and spread.

A pain rating is used to quantify a participant-reported experience at a defined point after surgery. A scale gives the study a common way to summarize responses across participants and compare the average scores between randomized groups. The fixed assessment time is important for interpretation: this endpoint describes pain at 30 minutes post-op, not pain across the entire postoperative period, pain at another time, or recovery overall.

The posted means are 2.5 points for preemptive local analgesia and 4.4 points for placebo. The standard deviations are 3.1 and 3.0 points, respectively. The endpoint summary does not report a distribution of individual scores, the proportion of participants at any particular score, or additional measures of pain. Nor does the registry record explain the administration details or measurement properties of the scale in this trial. The interpretation should therefore remain tied to the reported group averages and their stated time point.

7. Results Posted in the Registry

• Preemptive Local Analgesia (PLA): mean 2.50 versus 4.40 on control; difference -1.90 (95% CI -3.16 to -0.64), standardized effect d = -0.62; z-test p = 0.003.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted analysis compares average continuous pain scores between two parallel randomized groups. The registry reports a two-sided t-test and a mean difference in final values. These methods address whether the observed difference in group averages is compatible with a null model in which the population means are equal, while allowing departures in either direction.

What does the mean difference represent?

The mean difference is the PLA group mean minus the placebo group mean. In the posted results, the PLA mean is 2.5 and the placebo mean is 4.4, giving a reported difference of -1.9 points. Since lower values on this scale indicate less pain by its stated anchors, the negative direction describes a lower average score in the PLA group at the stated assessment time. This is a comparison of averages, not a count of participants who experienced a particular score or improvement.

A mean is useful when the outcome is measured numerically and the research question concerns average levels between groups. It compresses all scores in a group into one central summary, however, so it does not show whether scores cluster around the mean, include extreme observations, or form distinct subgroups. The standard deviation provides a summary of within-group spread but also does not display the full distribution. The reported standard deviations are 3.1 points for PLA and 3.0 points for placebo.

How should the t-test be understood?

A two-sided t-test assesses evidence for a difference in either direction rather than testing only whether one specified group has a higher or lower mean. The sponsor’s reported test gives p = .003. The re-calculation from the posted summaries gives an unadjusted p-value of 0.003. These values describe the result under the test’s statistical assumptions and null model. They are not the probability that the null hypothesis is true, the probability that the findings occurred by chance, or a measure of clinical importance.

General statistical explanation: a t-test for independent groups uses the difference between group means relative to the uncertainty in that difference. The uncertainty depends on the group sizes and variability. The posted groups each contain 45 participants, and their standard deviations are similar. The registry reports the sponsor’s method as a two-sided t-test; more detailed information about the exact implementation, such as variance handling or any adjustments, is not reported in the registry record.

What does the confidence interval add?

The sponsor reports a 95% confidence interval from -3.2 to -0.7 for the mean difference. A confidence interval communicates both the estimated direction and the precision of the estimate under the analysis assumptions. Here, the reported interval is entirely below zero, in keeping with the negative point estimate. It also shows that the data are compatible with a range of possible average differences, not only the point estimate of -1.9.

General statistical explanation: a confidence interval is produced by a procedure that, under repeated use and its assumptions, would cover the target parameter at the stated rate. It is not a statement that there is a 95% probability that this particular interval contains the true value. The interval describes uncertainty about the group-level mean difference, not the range of individual pain scores.

Why does variability matter?

General statistical explanation: variation among participants affects how precisely a group mean and the difference between group means can be estimated. More variability generally makes a mean difference less precise when sample size is unchanged. If data are more dispersed than a model assumes, a standard error based on that model may understate uncertainty. Over-dispersion is especially relevant when a model expects less variation than is present in the data. In this trial, the endpoint is continuous and the registry reports standard deviations, but it does not report a specific assessment of distributional assumptions or over-dispersion.

The group standard deviations summarize variation around each mean. Similar standard deviations do not mean every individual response was similar, and they do not rule out skewness or outliers. The posted aggregate results do not allow those features to be examined. The record also does not report whether assumptions were checked, whether any observations were excluded, or whether an alternative analysis was planned.

What does the re-calculation add?

The re-calculation is an unadjusted check based on the posted group summaries. It gives the same reported point difference, -1.9, and an unadjusted p-value of 0.003; its interval is close to the sponsor’s reported interval. The registry record does not flag a discrepancy. Because summary statistics cannot reproduce all details of a participant-level analysis, this check should be understood as a transparent comparison using the available group means, standard deviations, and sample sizes. It does not recover unreported modeling choices or missing-data procedures.

The sponsor’s reported result is based on the stated t-test. The record does not describe covariate adjustment, a transformation of the outcome, a rank-based analysis, or a model that accounts for repeated measurements. The endpoint is reported at one time point, and no further repeated-measure outcomes are listed. These methods are not implied by the available result and are not reported in the registry record.

How should statistical and clinical interpretation differ?

Statistical evidence concerns the compatibility of the observed result with a model; clinical interpretation concerns whether the size and context of a difference matter to participants or clinicians. A p-value and confidence interval can inform the first question, but the registry record does not provide a threshold for a clinically important difference. It also does not report participant-level judgments, longer-term outcomes, or a wider assessment of benefits and harms. Therefore, the methods support describing the early group-average contrast and its statistical uncertainty, while leaving broader judgments outside what these posted results establish.

10. Confidence Intervals and Precision

The sponsor-reported 95% confidence interval for the mean difference runs from -3.2 to -0.7 points. The point estimate is -1.9 points, with the difference defined as PLA minus placebo. The entire reported interval is below zero, matching the direction of the observed means: 2.5 points for PLA and 4.4 points for placebo.

The interval is useful because it expresses uncertainty around the average difference. It shows that the observed data are compatible with a range of negative differences under the stated analysis, rather than pinning down a single exact population value. It does not mean that 95% of participants’ individual scores fall between -3.2 and -0.7; those numbers refer to the group-level mean difference. Nor does the interval by itself establish whether any particular difference is important in practice. The registry record does not report a threshold for interpreting clinical importance.

Precision depends on the amount of information in the trial and the variability of the outcome. Each group has 45 participants, with standard deviations of 3.1 and 3.0 points. The reported interval reflects the sponsor’s analysis of the observed data. The re-calculated interval is close to the sponsor-reported interval, and the registry record does not flag a discrepancy. The sponsor’s analysis should be used as the principal posted estimate.

General statistical explanation: a 95% confidence interval is a property of a method across repeated studies under its assumptions; it is not a 95% probability statement about the fixed effect in this one trial. The interval also does not address possible bias from missing data, measurement, or other design features. Those aspects require information beyond the interval, and relevant details are 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 sample-size table and curve are planning illustrations based on the observed effect, not the trial’s original design assumptions. The table reports participants per arm, not total events. The planning calculation uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses an effect that is a stated fraction of the observed effect.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect under the planning model, if that effect is real and the assumptions hold. The 90% power column gives the corresponding illustrative number per arm for a design with a 90% chance. These are planning probabilities under a model, not guarantees about a future study’s result. The figures are not observed power.

The table includes planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For the observed effect, the illustrations are 41 participants per arm for 80% power and 55 participants per arm for 90% power. For planning at 75% of the observed effect, they are 72 and 97 participants per arm, respectively. For planning at 50% of the observed effect, they are 162 and 217 participants per arm, respectively. The curve presents the same general planning relationship visually.

Smaller effects are harder to distinguish from random variation, so they require more participants under otherwise unchanged assumptions. These calculations use the effect observed in this trial as their reference point; they do not show what effect the original investigators expected or what assumptions they used when setting the trial enrollment. The trial’s original sample-size justification and design assumptions are 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 3.050.
2. n = 2 × (1.96 + 0.842)² × 3.050² / -1.900² = 40.5, rounded up to 41 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 <- -1.9                      # observed difference in means
sigma <- 3.05040980853393                     # 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(318292)
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 = 41 (80% power), 55 (90% power)
 75% of observed effect: n per arm = 72 (80% power), 97 (90% power)
 50% of observed effect: n per arm = 162 (80% power), 217 (90% power)
power.t.test: 41.4 
Simulated power at n = 41 per arm: 0.797 (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. Analyses Reported by the Sponsor

The sponsor-reported analysis is a two-sided t-test comparing final mean values. It reports a mean difference of -1.9 points, a 95% confidence interval from -3.2 to -0.7, and p = .003. The re-calculation using the posted group summaries gives a mean difference of -1.9 and an unadjusted p-value of 0.003, with a confidence interval close to the sponsor’s interval.

The registry record does not flag a discrepancy between the posted analysis and the re-calculation. The agreement supports the conclusion that the group summaries and the sponsor’s stated result are consistent at the level visible in the registry. The re-calculation is not a reconstruction of participant-level data and cannot verify unreported analysis decisions, handling of missing values, or any adjustments not described in the record.

For interpretation, the sponsor’s own analysis takes precedence over the summary-statistic re-calculation. It is the analysis explicitly reported in the registry, and it provides the posted test result and confidence interval. The recalculation is best treated as a transparent cross-check rather than an alternative claim about the trial’s findings.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one reported analysis, and it lists no secondary posted outcomes. The primary outcome is the mean VAS pain score at 30 minutes post-op. These registry entries make the scope of the posted results relatively focused, but they do not establish what outcomes or analyses may have been planned in the original protocol.

Multiplicity arises when many outcomes, time points, subgroups, or statistical tests are examined. Repeated testing can increase the chance of finding an apparently notable result even when no underlying difference exists. General statistical explanation: analysis plans often address multiplicity by specifying a primary endpoint, limiting confirmatory tests, or adjusting inference across several comparisons. Whether the trial used such an approach is not reported in the registry record. No multiplicity adjustment is described in the posted analysis.

The reported test is a two-sided t-test for the group difference in final values. The registry does not describe any additional outcome tests, subgroup analyses, covariate adjustments, or interim analyses. Their presence or absence in the original analysis plan is not reported in the registry record. The single posted analysis should not be taken as proof that no other analyses were undertaken.

The registry does not report the amount or pattern of missing endpoint data, how missing values were handled, or whether all randomized participants contributed to the primary analysis. The group summaries list 45 participants in each arm, but the analysis population and the link between those group counts and participants with observed endpoint data are not specified. It is therefore not possible to confirm whether the analysis followed an intention-to-treat principle, a per-protocol approach, or another population definition. Those details are not reported in the registry record.

Missingness can affect interpretation if participants without recorded scores differ from those with scores. General statistical explanation: the consequences depend on why data are missing and on the analysis method; simply having a complete-case summary does not resolve that concern. The registry does not provide enough information to assess whether missingness could have influenced the posted comparison. The appropriate interpretation is limited to the reported results and their stated analysis, with the unreported analysis-population and missing-data details kept as open questions.

15. 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: postoperative pain requiring readmission (4.4%), atrial fibrillation (2.2%), bacterial infection (2.2%), hypoxia (2.2%), pneumonia (2.2%).

The serious adverse event summary lists 5 of 45 participants in the preemptive local analgesia group and 3 of 45 participants in the placebo group as affected. The registry also lists other adverse events for 18 of 45 participants in the PLA group and 22 of 45 participants in the placebo group. These are the posted group counts; they are not a statistical comparison, and the registry does not provide a test or confidence interval for them.

The most frequently listed serious-event terms include Postoperative Pain Requiring Readmission at 4.4%, followed by Atrial Fibrillation, Bacterial Infection, Hypoxia, Pneumonia, and Postoperative Nausea and Vomiting Requiring Readmission, each at 2.2%. The record does not explain the denominator or provide additional event-level detail for these percentages. It is not possible from this summary to determine timing, duration, severity beyond the serious-event classification, or whether an event was judged related to an intervention.

Deaths are not reported in the registry record. The event summary should be read as a descriptive account of the entries posted for each arm, not as evidence that one assignment caused or prevented an event. The sample and the limited registry detail also constrain comparisons of uncommon events. These data do not provide a complete safety assessment.

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

The posted primary result is a lower average VAS pain score in the preemptive local analgesia group than in the placebo group at 30 minutes post-op. The group means are 2.5 and 4.4 points, and the sponsor-reported mean difference is -1.9 points. Its 95% confidence interval runs from -3.2 to -0.7, and the reported two-sided p-value is .003. The re-calculation from the group summaries is consistent with that analysis, and the registry record does not flag a discrepancy.

This is evidence about a group-average difference at one early postoperative assessment. It does not show that every participant assigned to PLA had a lower score than every participant assigned to placebo. The standard deviations of 3.1 and 3.0 points indicate variation within both groups, while the registry summaries do not display individual scores or their distribution.

The result does not establish how scores changed over time, whether any difference persisted, or how other aspects of recovery compared. No secondary outcomes are posted. The record does not give a threshold for a clinically important pain-score difference, so the size of the estimated contrast cannot be classified as important or unimportant on the basis of this registry entry alone.

Nor does the result answer every question about the intervention or the procedure. Details about eligibility, participant characteristics, outcome-data completeness, analysis populations, and several protocol and analysis decisions are not reported in the registry record. The serious adverse event summary is descriptive and does not establish causal relationships. These limitations mean the findings should be read narrowly: as a randomized-group comparison of average pain scores at 30 minutes post-op, with the uncertainty and reporting gaps.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates how an endpoint, an estimated group difference, and uncertainty fit together. The endpoint is a continuous pain score at a clearly stated time. The mean difference summarizes the contrast between randomized groups, while the confidence interval shows that the estimate is not exact. The p-value addresses compatibility with a null model, but does not express the size or practical importance of the contrast.

The direction of the difference is straightforward to interpret once the subtraction order is stated: PLA minus placebo is negative, and the PLA group has the lower posted mean. Without naming that order, a negative difference can be confusing. Showing the scale anchors and assessment time also keeps the result tied to what was measured rather than allowing it to stand in for pain or recovery in general.

The record also provides an opportunity to distinguish a sponsor-reported analysis from a re-calculation based on summary statistics. Here they align closely, and no discrepancy is flagged. That alignment supports a transparent reading of the posted result, but it does not recover unreported participant-level decisions. The sample-size illustrations make a related distinction: planning numbers based on the observed effect can help explain how smaller target effects require larger planned groups, but they are not observed power and do not reveal the original design justification.

Finally, the registry’s reporting boundaries are part of the statistical interpretation. Details about missing data, analysis populations, multiplicity, masking roles, and the original sample-size rationale are not reported. Recognizing these gaps helps readers distinguish what the posted comparison directly shows from what remains unknown.

18. 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 gives limited information about the study population. It describes vaginal hysterectomy with suspension sutures, but eligibility criteria, participant characteristics, and the setting are not reported in the registry record. This limits assessment of how well the enrolled participants represent other groups or clinical contexts.

The primary outcome is measured at 30 minutes post-op only. The record lists no secondary posted outcomes, so it does not show whether the group comparison was similar at later times or on other outcomes. It also does not report the minimum difference considered important for the VAS score. Without that context, the statistical result does not settle the practical significance of the observed mean difference.

Although the trial is labeled randomized and quadruple masked, the registry does not report the sequence-generation or allocation-concealment procedures, the roles covered by masking, or how masking was maintained. The analysis is reported as a two-sided t-test, but details about assumption checks, missing-data handling, the analysis population, and any adjustments are not reported in the registry record. The original sample-size justification and any interim analysis plan are also not reported.

The posted group summaries do not show participant-level scores or the distribution of the continuous outcome. The record therefore does not allow readers to inspect outliers, skewness, or patterns within the groups. The adverse-event summary provides counts and selected serious-event terms, but not enough detail to assess event timing, relatedness, or a statistically adjusted comparison. These limitations do not erase the posted result; they define how narrowly it should be interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Preemptive Local Anesthesia in Vaginal Surgery — NCT00318292.
• Registry record last updated 2010-11-18; status last verified 2010-10.
• Results first posted 2009-03-18.
• 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.

22. Record Summary

This completed Phase 4 trial is listed as randomized, parallel-group, and quadruple masked, with enrollment of 90. It compares preemptive local analgesia using bupivacaine and epinephrine with placebo before vaginal hysterectomy with suspension sutures.

The primary endpoint is the VAS pain score at 30 minutes post-op, on a scale from 0 (None) to 10 (Worst). The posted means are 2.5 for PLA and 4.4 for placebo. The sponsor reports a mean difference of -1.9, a 95% confidence interval from -3.2 to -0.7, and p = .003. The re-calculation is consistent with the posted analysis, and no discrepancy is flagged.

The result describes an early group-average comparison, not individual experiences or outcomes over time. No secondary outcomes are posted. Important details about the original design assumptions, missing data, analysis populations, and other analysis procedures are not reported in the registry record.