Topical Anesthetic Use In Pessary Management: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Anesthetic Use In Pessary Management (NCT02380742), a randomized phase 2 study. The primary outcome is VAS Score at the Time of Pessary Removal Adjusting for Baseline Pain.

2. Clinical Question

The clinical question is whether lidocaine-prilocaine cream is associated with a different level of self-reported pain than placebo cream when a vaginal pessary is removed. The registry also describes pain and discomfort at insertion as part of the study purpose, but the primary endpoint is pain at removal.

Pain intensity was recorded on a scale from 0 to 10, where 0 means no pain and 10 means the worst pain. A lower score therefore represents less reported pain on that scale. The primary comparison is an adjusted comparison of group means, rather than a count of participants who did or did not experience pain.

The randomized, double-blinded, placebo-controlled design is intended to compare the groups while limiting the influence of allocation decisions and expectations. The registry record does not report additional eligibility criteria, the details of how pain was recorded, or a threshold defining a clinically important difference. Those details should not be inferred from the observed group means.

3. Trial Design

This was a randomized, double-blinded, parallel-group, placebo-controlled trial listed as Phase 2. Loyola University is the sponsor. The record lists enrollment of 54 and a completed status. The recorded study start is 2015-07 and the primary completion is 2016-02.

One group received 4 mL of lidocaine-prilocaine cream and the other received 4 mL of placebo cream. The registry describes the study as double blinded but does not specify which roles were masked or how masking was maintained. The exact method of random sequence generation and allocation concealment is not reported in the registry record.

The primary endpoint concerns pain at pessary removal. The outcome groups contributing to that analysis are listed as 27 for lidocaine-prilocaine and 26 for placebo. The registry also reports three secondary outcomes: removal pain adjusted for pessary type and investigator training; removal pain adjusted for baseline pain and patient age; and insertion pain adjusted for baseline pain. The listed group counts for the insertion outcome are 27 and 25. Reasons for the variation in outcome counts are not reported in the registry record.

The record does not report the original sample-size justification, planned recruitment targets by group, timing or frequency of cream application, follow-up schedule, or interim analyses. It also does not give enough detail to establish whether the posted outcome groups represent every randomized participant or a defined analysis population. These absences limit how fully the trial’s conduct and analysis can be reconstructed from the registry information.

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:

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 VAS Score at the Time of Pessary Removal Adjusting for Baseline Pain, measured over Removal of Pessary.

The primary endpoint is self-reported pain intensity at the time of pessary removal, adjusted for baseline pain. Pain is measured on a 0-to-10 scale, with 0 representing no pain and 10 representing the worst pain. The reported unit is centimeters, and the analysis parameter is a least-squares mean.

A pain rating captures the participant’s own experience, which is the subject of the endpoint. It is continuous rather than a simple event count: the analysis compares average scores between the cream groups. The adjusted least-squares means are 1.76 for lidocaine-prilocaine and 3.81 for placebo. Their reported standard errors are 0.57 and 0.58, respectively. These standard errors describe uncertainty around the estimated group means; they are not the spread of individual pain scores.

Adjusting for baseline pain aims to account for differences in participants’ pain ratings before the endpoint assessment. In general, an adjusted comparison can estimate the group contrast while accounting for the specified baseline measure. The registry record does not provide the full model specification, the baseline measurements, or other model diagnostics.

The scale gives direction to the result: lower values correspond to less reported pain. However, the registry record does not report a threshold for a clinically important difference, so the size of a score contrast alone does not establish how participants would judge its importance. Nor does the endpoint measure other aspects of pessary management beyond the specified pain rating at removal.

7. Results Posted in the Registry

• Lidocaine-prilocaine: mean 1.76 versus 3.81 on control; difference -2.05 (95% CI -3.64 to -0.46), standardized effect d = -0.69; z-test p = 0.012.

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.

VAS Score at the Time of Pessary Removal Adjusting for Pessary Type and Investigator Training

• 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:
  • Lidocaine-prilocaine: mean 1.81 versus 3.76 on control; difference -1.95 (95% CI -3.60 to -0.30), standardized effect d = -0.64; z-test p = 0.020.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Lidocaine-prilocaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

VAS Score at the Time of Pessary Removal Adjusting for Baseline Pain and Patient Age

• 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:
  • Lidocaine-prilocaine: mean 1.88 versus 3.69 on control; difference -1.81 (95% CI -3.43 to -0.19), standardized effect d = -0.60; z-test p = 0.029.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Lidocaine-prilocaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

VAS Score at the Time of Pessary Insertion Adjusting for Baseline Pain

• 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:
  • Lidocaine-prilocaine: mean 0.61 versus 1.68 on control; difference -1.07 (95% CI -2.28 to 0.14), standardized effect d = -0.48; z-test p = 0.082.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lidocaine-prilocaine and the control. The interval gives the range of effects that remain compatible with the data.

Across the three secondary outcomes, the recalculated estimates are in the same direction as the primary contrast: lower pain scores for lidocaine-prilocaine under the stated subtraction order. The two secondary analyses of pain at removal have intervals lying below zero. The secondary analysis of pain at insertion has an interval that includes zero. Taken together, the secondary results are directionally consistent for removal pain, while the insertion estimate is less conclusive in relation to zero.

These secondary endpoints address related but not identical questions. The removal analyses use different adjustment variables, while the insertion endpoint concerns pain at a different stage of pessary management. They can provide context for the primary result, but they are not substitutes for the prespecified primary endpoint. Their estimates also remain subject to the uncertainty associated with the recorded group counts and the analysis methods.

Unadjusted secondary results carry less weight when the registry record does not report a plan for controlling multiplicity or a hierarchy of testing. In general, testing several outcomes creates more opportunities for a result to appear noteworthy by chance. The record lists three secondary outcomes but does not report whether their analyses were confirmatory, how they were prioritized, or whether any multiplicity adjustment was used.

Accordingly, the secondary pattern may be described as supportive context, not as independent confirmation of a treatment effect. The posted results do not establish that every outcome is affected similarly, and the registry record does not report a clinically important threshold for interpreting the size of any contrast.

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

• VAS Score at the Time of Pessary Removal Adjusting for Pessary Type and Investigator Training
• VAS Score at the Time of Pessary Removal Adjusting for Baseline Pain and Patient Age
• VAS Score at the Time of Pessary Insertion Adjusting for Baseline Pain

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: a pain score on a 0-to-10 scale. The posted group summaries are least-squares means, a form of model-based average. The reported standard errors express uncertainty in each estimated mean. They do not describe the range of individual participants’ scores.

What does adjustment for baseline pain mean?

In general, an adjusted analysis includes a specified participant characteristic in the statistical model. Here, baseline pain is the stated adjustment variable for the primary endpoint. The intent is to compare groups while accounting for that measure, rather than relying only on raw group averages. The registry identifies the method as ANCOVA, a model commonly used to compare a continuous outcome between groups while adjusting for one or more covariates. The full model formula, covariate coding, assumptions checks, and missing-data method are not reported in the registry record.

The primary reported least-squares means are 1.76 for lidocaine-prilocaine and 3.81 for placebo. The corresponding standard errors are 0.57 and 0.58. These are adjusted group estimates, whereas the simple recalculation uses the posted summaries to form an unadjusted group contrast. A recalculation from summaries cannot reproduce every feature of the sponsor’s fitted model.

What does the recalculated contrast represent?

The recalculated primary contrast is -2.05, defined as lidocaine-prilocaine minus placebo. It is a simple, unadjusted re-calculation from posted summary statistics, not an alternative ANCOVA model. The accompanying p-value, 0.012, is likewise an unadjusted recalculation. The estimate’s sign depends on the order of subtraction; a negative value in this stated direction means the lidocaine-prilocaine group’s posted mean is lower. The sponsor’s reported ANCOVA is a separate analysis, with its own reported mean difference of 2.87 and p = .02.

In general, a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The recalculated p-value should not be substituted for the sponsor’s reported analysis. The registry record does not provide the full analysis plan needed to explain every difference between the two results.

Why does uncertainty matter?

In general, a confidence interval gives a range of values compatible with the data and model at a stated confidence level. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty about the contrast. The recalculated primary interval lies below zero, but it still spans a range of possible effect sizes. The registry record does not state the confidence level for the recalculated intervals, so no level should be assumed from the registry information alone.

Standard errors and intervals are related, but they answer different reporting needs. The standard errors attached to the group means describe uncertainty around each mean. An interval for a group contrast describes uncertainty around the difference between groups. Neither should be confused with the variability of individual responses.

What does an unadjusted secondary p-value tell us?

General statistical practice treats a set of secondary comparisons cautiously when no adjustment for multiple testing is reported. Examining several outcomes can increase the chance that at least one result appears noteworthy by chance. The registry lists three secondary outcomes, but multiplicity procedures and a hierarchy of testing are not reported in the registry record. Therefore, secondary p-values should be read as descriptive evidence rather than definitive confirmation.

These methodological explanations are general. The registry record does not report the trial’s complete statistical analysis plan, model diagnostics, handling of missing values, interim analyses, or original sample-size justification. Those details should not be inferred from the posted results.

11. Confidence Intervals and Precision

The recalculated primary group contrast is -2.05, with an interval that lies below zero. This direction is consistent with a lower pain score for lidocaine-prilocaine than placebo under the stated subtraction order. The interval conveys uncertainty about the size of that contrast; it is not a guarantee that the true effect falls within a fixed range, and it does not establish clinical importance.

The group means also have reported standard errors: 0.57 for lidocaine-prilocaine and 0.58 for placebo. A standard error describes how precisely a mean is estimated, rather than how much pain scores vary from participant to participant. The registry record does not report standard deviations for the primary outcome or the confidence level for the recalculated interval.

For the secondary removal endpoint adjusted for pessary type and investigator training, the recalculated contrast is -1.95 and its interval lies below zero. For the endpoint adjusted for baseline pain and patient age, the recalculated contrast is -1.81 and its interval also lies below zero. The insertion endpoint has a recalculated contrast of -1.07, but its interval includes zero. These intervals reflect estimation uncertainty; they do not by themselves determine clinical relevance or prove that an effect is absent when an interval includes zero.

Precision is constrained by the outcome group counts recorded for these analyses. The primary results list 27 and 26 participants, and the insertion outcome lists 27 and 25. The registry record does not explain the different counts or report a missing-data analysis. As a result, the effect of incomplete outcome information on precision cannot be assessed from the record.

In general, a confidence interval is more informative than a p-value alone because it describes both the direction and range of plausible estimates under the model. Here, the record’s reporting does not include the confidence level for the recalculated intervals, so their numerical limits should not be interpreted as a specified confidence level.

12. Planning a Similar Trial: Sample Size

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

The planning illustrations give participants per arm, not a combined total and not total events. They are illustrative calculations based on the observed effect, rather than the trial’s original design assumptions. The assumptions listed for these calculations are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the assumed effect under those assumptions, if that effect were present. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are planning illustrations, not observed power.

For the primary endpoint, the illustration using 100% of the observed effect gives 33 participants per arm for 80% power and 44 participants per arm for 90% power. Planning for 75% of the observed effect gives 59 participants per arm for 80% power and 78 participants per arm for 90% power. Planning for 50% of the observed effect gives 131 participants per arm for 80% power and 176 participants per arm for 90% power.

The pattern reflects a general statistical principle: smaller effects are harder to distinguish from random variation, so detecting them with the same target power requires more participants. These figures should not be read as the trial’s planned enrollment or as evidence that the completed trial had a particular probability of success. The original sample-size justification and 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 = -2.050; pooled standard deviation σ = 2.960.
2. n = 2 × (1.96 + 0.842)² × 2.960² / -2.050² = 32.7, rounded up to 33 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.05                      # observed difference in means
sigma <- 2.95966280538318                     # 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(2380742)
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 = 33 (80% power), 44 (90% power)
 75% of observed effect: n per arm = 59 (80% power), 78 (90% power)
 50% of observed effect: n per arm = 131 (80% power), 176 (90% power)
power.t.test: 33.7 
Simulated power at n = 33 per arm: 0.787 (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 the sponsor’s primary analysis as ANCOVA, with a mean difference of 2.87 and p = .02. This is the trial’s reported analysis output. The record does not provide a confidence interval for that estimate or enough detail about the contrast coding and complete model specification to interpret the sign directly against the recalculated contrast.

The recalculation from the posted summary statistics expresses the contrast as lidocaine-prilocaine minus placebo. It gives -2.05 and an unadjusted p-value of 0.012. The sponsor’s reported analysis and the recalculation are not interchangeable: the former is an ANCOVA output, while the latter is a simple unadjusted calculation from posted summaries. Differences in model adjustment or contrast direction can affect how numerical results are expressed, but the registry record does not report enough detail to attribute the numerical difference to a specific cause.

The sponsor result should therefore be reported as the sponsor’s own ANCOVA analysis, and the recalculated result should be identified as an unadjusted approximation. Neither value should be silently substituted for the other. The record does not report the analysis plan needed to establish whether additional model details account for their relationship.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes. It reports four outcome measures and four analyses. The primary result concerns pain at pessary removal adjusted for baseline pain. The secondary analyses use other adjustment variables for removal pain and assess pain at insertion. The record does not report a prespecified testing hierarchy or a method for adjusting for multiple comparisons.

In general, multiplicity matters because repeated statistical tests can increase the chance of at least one result appearing unusual under a null model. Without a reported approach to this issue, the secondary p-values should be treated cautiously and should not be interpreted as if they were the sole confirmatory test. The registry record does not report whether the primary outcome was the only outcome intended for formal hypothesis testing.

The outcome counts differ across the posted results: the primary removal analysis lists 27 and 26 participants, while the insertion analysis lists 27 and 25. The record does not report why these counts differ, whether all randomized participants were included in each analysis, or how missing outcome values were handled. It is therefore not possible to determine from the registry record whether missingness could have affected the estimates.

The analysis population definitions, protocol deviations, sensitivity analyses, interim analyses, and original sample-size justification are also not reported in the registry record. These omissions limit assessment of whether the posted analyses follow a prespecified plan and how robust the results are to alternative assumptions. They do not establish that an analysis was or was not performed; they mean that the relevant 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 5% reporting threshold.

The serious adverse event figures report zero affected participants in the lidocaine-prilocaine group, with 27 listed as at risk, and zero affected participants in the placebo group, with 26 listed as at risk. The registry record lists no serious adverse event terms for either group.

The other adverse event figures also report zero affected participants in each group: the at-risk counts are 27 for lidocaine-prilocaine and 26 for placebo. These entries describe what is posted in the registry record. They do not establish that no symptoms or events of any kind occurred outside the categories or reporting available in that record.

Death counts are not reported in the registry record. The record also does not provide event definitions, severity grading details, follow-up duration for safety, or information about how adverse events were collected. The zero counts should therefore be read as the posted adverse event results, not as a comprehensive assurance about safety or an estimate of rare-event risk.

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

The posted results show lower adjusted mean pain scores at pessary removal for lidocaine-prilocaine than for placebo. The primary least-squares means are 1.76 and 3.81, and the simple recalculated contrast is -2.05 when expressed as lidocaine-prilocaine minus placebo. The sponsor’s reported ANCOVA gives p = .02. These statistics describe the recorded outcome and its analysis; they do not, by themselves, establish the clinical importance of the difference.

The scale runs from 0, no pain, to 10, worst pain, so lower values indicate less reported pain. The registry record does not report a minimum difference that participants or clinicians would consider meaningful. It also does not report enough information about the analysis population, missing outcomes, or full model specification to resolve all uncertainties in the interpretation.

The findings apply to the measured pain outcomes in this randomized, double-blinded, placebo-controlled trial. They do not establish effects on other aspects of pessary management, longer-term outcomes, or populations not described in the registry record. The secondary outcomes offer related context, but their unadjusted status and the absence of reported multiplicity procedures limit their confirmatory weight.

In general, statistical evidence should be interpreted alongside design, precision, outcome definition, and clinical context. Here, the interval for the recalculated primary contrast lies below zero, while still allowing uncertainty about the magnitude. A statistically notable result is not equivalent to proof of a clinically important effect, and the posted results should not be turned into medical advice.

18. Why This Trial Matters Statistically

This trial illustrates why the form of an outcome and the analysis attached to it matter. Pain is recorded as a continuous score, and the primary result is expressed as adjusted group means rather than as the number of participants crossing a threshold. That makes the estimated contrast interpretable in the scale’s units, while leaving the clinical importance of that contrast dependent on a threshold not reported in the registry record.

It also illustrates the distinction between a sponsor’s fitted analysis and a summary-statistic recalculation. The registry reports an ANCOVA result, while the recalculation is explicitly unadjusted. Keeping those outputs separate avoids presenting a simple approximation as though it reproduced the trial’s model. The difference in their reported values also highlights why contrast direction and model details are important for transparent reporting.

Finally, precision, secondary outcomes, and safety reporting all shape interpretation. The primary interval lies below zero, but uncertainty remains about effect size. The secondary outcomes broadly point in the same direction, yet their multiplicity handling is not reported. The posted adverse event counts are zero, but the registry record does not report all the detail needed to characterize safety comprehensively.

For biostatistical readers, the record is a reminder that a result is not only a point estimate or p-value. It is also the product of a design, an outcome definition, a model, and reporting choices. When key analysis details are absent, conclusions need to remain within the boundaries of what the record states.

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 gives limited detail about eligibility, treatment timing, randomization procedures, allocation concealment, and who was masked. Although the trial is described as randomized and double blinded, those operational details are not reported. The record also does not report the full protocol or statistical analysis plan.

The primary ANCOVA output includes a reported mean difference and p-value but no confidence interval. The model specification and contrast coding are not reported in enough detail to reconcile its numerical presentation with the unadjusted recalculation. The recalculated intervals do not have a confidence level stated in the registry record. These reporting gaps limit assessment of the estimate’s precision and the relationship between analyses.

Outcome counts vary between the removal and insertion analyses, and reasons for the variation are not reported. The registry record does not describe missing-data handling, analysis populations, protocol deviations, or sensitivity analyses. It therefore cannot establish how incomplete outcome data may have influenced the estimates.

The record lists secondary outcomes but does not report multiplicity adjustment or a testing hierarchy. Nor does it provide a clinically important difference threshold for the pain scale. These omissions make it difficult to judge the confirmatory status of secondary findings and the practical importance of the estimated contrasts.

The listed enrollment is 54, but the original sample-size rationale and design assumptions are not reported. The planning illustrations based on observed effects cannot fill that gap. Safety reporting is also limited: zero adverse events are posted for the listed categories, while death counts and further event-collection details are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Topical Anesthetic Use In Pessary Management — NCT02380742.
• Registry record last updated 2017-02-23; status last verified 2017-01.
• Results first posted 2017-02-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT02380742 is a completed, randomized, double-blinded, parallel, placebo-controlled Phase 2 trial sponsored by Loyola University. It evaluated 4 mL of lidocaine-prilocaine cream against 4 mL of placebo cream during vaginal pessary management.

The primary endpoint was pain at pessary removal, adjusted for baseline pain, on a 0-to-10 scale. The posted least-squares means were 1.76 for lidocaine-prilocaine and 3.81 for placebo. The sponsor’s reported ANCOVA gives a mean difference of 2.87 and p = .02; the unadjusted recalculation gives a contrast of -2.05 and p = 0.012 under the lidocaine-prilocaine-minus-placebo direction.

Three secondary outcomes address removal pain under other adjustments and insertion pain. The registry record does not report multiplicity procedures, missing-data handling, the full analysis plan, or the original sample-size justification. The posted adverse event counts are zero in both groups for serious and other adverse events; death counts are not reported in the registry record.