Treatment of Prepubertal Labial Adhesions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Prepubertal Labial Adhesions (NCT02218463), a randomized na study. The primary outcome is Complete Resolution of Labial Adhesion..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with quadruple masking. It lists 43 participants as enrolled and identifies Children’s Mercy Hospital Kansas City as the sponsor. The study is marked completed. Its recorded start is 2014-09, and primary completion is recorded as 2016-05. The phase is listed as NA.

The two intervention groups were Cetaphil and estradiol cream 0.01%. Both arm descriptions specify applying a pea-sized amount to the adhesion with lateral traction twice daily. The record does not describe whether participants, caregivers, clinicians, outcome assessors, or analysts were the masked parties; those details are not reported in the registry record. The method used to generate the random sequence, the allocation-concealment procedure, and any stratification factors are also not reported in the registry record.

The primary outcome was complete resolution of labial adhesion, measured as a count of participants, with assessments scheduled at 3 weeks and 6 weeks after treatment initiation. The record also lists a secondary outcome, Composite Severity Scale of Labial Adhesion Over Time. It gives no fuller description of that measure in the posted information. The registry records 2 outcome measures and 4 analyses, but does not identify a complete analysis plan or explain how the two primary assessment times were handled in the reported test.

Randomization and masking are design features intended to reduce bias, but the registry record does not provide enough procedural detail to evaluate their implementation. A parallel design assigns participants to one group rather than describing a crossover. Further details about follow-up, adherence, and participant flow are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Complete Resolution of Labial Adhesion., measured over 3 weeks and 6 weeks.

The primary endpoint is complete resolution of labial adhesion, recorded as a count of participants. The registry specifies assessments at 3 weeks and 6 weeks after treatment starts. This is a binary type of outcome at a given assessment: each participant is classified according to whether complete resolution has occurred. The record does not provide a more detailed operational definition of complete resolution, such as how the boundary between complete and incomplete resolution was judged.

Complete resolution is used to represent whether the adhesion has fully resolved by the scheduled assessment, rather than recording only a change in severity. That makes the endpoint directly interpretable as a participant-level event. The listed secondary outcome, Composite Severity Scale of Labial Adhesion Over Time, represents a different kind of question: change in a severity measure across time. Details of its scoring and analysis are not reported in the registry record.

Assessments at 3 weeks and 6 weeks could describe status at distinct follow-up times, but the record does not clarify whether the reported count and test correspond to one time, both times, or a particular rule combining them. It also does not state whether resolution at the earlier assessment had to persist to the later assessment. Those details matter when interpreting a binary endpoint measured repeatedly, because counts at separate visits do not automatically represent the same estimand.

7. Results Posted in the Registry

• Estradiol Cream 0.01%: 100.0% (22/22) versus 100.0% (21/21) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group design and reports a Fisher Exact test for a superiority analysis. The primary endpoint is a participant count for complete resolution, a binary outcome at an assessment. A Fisher exact test is a method for comparing categorical outcomes between groups. In general, it evaluates the compatibility of a contingency table with a null hypothesis of no association, using the observed group totals. Its use does not require a large-sample approximation to the test distribution, which can be useful when event counts are small. The registry record does not provide the full contingency table for the sponsor analysis or state which assessment time was used.

The posted results also permit a simple, unadjusted recalculation of the risk difference from the arm-level summaries. A risk difference expresses the difference between the two event proportions on the absolute probability scale. The posted recalculation is 0.0, with limits of 0.0 and 0.0. Those values are not the same thing as a confidence interval reported by the sponsor: the registry record gives no confidence interval for the Fisher Exact analysis. Because the reported counts equal the respective arm sizes, the summary-based recalculation does not reveal how the sponsor’s reported p-value of 0.206 was obtained.

What does an unadjusted comparison mean?

General explanation: an unadjusted comparison uses the observed group summaries without controlling for other participant characteristics or design variables. It is not necessarily the same as a model-based or stratified analysis. The registry does not report covariate adjustment, stratification, or a model for the primary outcome. The recalculated risk difference therefore describes only the simple contrast represented by the posted summaries, not a claim about an adjusted treatment effect.

Why does the distinction between a count and an event proportion matter?

The endpoint is recorded as a count of participants, while the comparison is expressed as a risk difference. A count alone depends on how many participants are included in each arm; a proportion relates event counts to group totals. The arm summaries include both the counts and totals, allowing the displayed comparison to be interpreted as a difference in proportions. General explanation: when group totals differ, comparing raw counts can be misleading because a larger group may have more events simply because it contains more participants. The risk difference places the groups on a common probability scale.

What does the p-value tell the reader?

General explanation: a p-value is calculated under a null hypothesis and a statistical model. It measures how unusual the observed data, or data more extreme under the test statistic, would be if that null model held. It is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of a difference. The reported p = 0.206 belongs to the registry-listed Fisher Exact analysis. Since the underlying table and outcome time are not specified, the record does not permit a complete independent reconstruction of that test.

What role does randomization play?

General explanation: random assignment can help balance measured and unmeasured prognostic factors across groups on average, reducing confounding in comparisons. It does not guarantee balance in a particular trial, especially when enrollment is limited, and it does not remove bias from missing outcomes or outcome assessment. The record reports randomization and quadruple masking but does not report the sequence-generation or concealment procedures, participant flow, or masking roles. Those omissions limit assessment of how the design was carried out.

How should repeated assessments be handled?

The primary outcome has two assessment times, 3 weeks and 6 weeks, while the reported analysis description gives one Fisher Exact result. General explanation: repeated measurements on the same participant are related, so treating measurements from one person as independent observations can misrepresent uncertainty. A prespecified approach might compare groups at a selected time or model the repeated pattern, but the particular method cannot be inferred from this record. The registry does not say which time point underlies the reported analysis, whether both were analyzed, or how any multiplicity from multiple assessments was handled.

The record lists a secondary composite severity measure over time, but does not give its results or analytical details in the registry record for interpretation. It also does not report a statistical analysis plan, missing-data method, analysis population, covariate adjustment, or sample-size justification. General explanation: over-dispersion matters when the variability in count data exceeds what a chosen count model expects, because standard errors based on the narrower model can be too small. No count-regression model or over-dispersion assessment is reported, and the binary complete-resolution endpoint does not by itself establish that such a model was used.

10. Confidence Intervals and Precision

Precision describes how much uncertainty surrounds an estimated effect. A confidence interval gives a range of values compatible with the data and the method used to calculate it, under the model’s assumptions. It is not a guarantee that the true effect lies in the interval, and a narrow interval is not automatically evidence that the study was well designed or that the estimate is unbiased.

For the simple unadjusted recalculation from the posted arm summaries, the risk difference is 0.0 and the confidence limits are 0.0 to 0.0. These are the values reported for that recalculation. They should be interpreted cautiously because the posted counts are 21 of 21 and 22 of 22, while the sponsor’s reported Fisher Exact test has p = 0.206. The registry record does not explain why these summaries and the reported test do not align, nor does it provide confidence limits for the sponsor analysis.

The recalculated interval should not be taken as evidence of perfect precision. Its degenerate limits arise from the form of the summary-based calculation when both displayed groups have all participants recorded with the event. The registry does not provide additional information about the outcome coding, assessment time, missing observations, or the underlying data needed to judge whether this summary represents the complete endpoint analysis. It also does not report an interval from the sponsor’s test that could be compared directly.

The reported p-value alone does not communicate the range of plausible treatment differences. Without a sponsor-reported interval and without a clear link between the p-value and the posted arm counts, the precision of the sponsor’s estimated effect is not reported in the registry record. The arm sizes and event pattern are descriptive, but they do not settle the unresolved uncertainty about the analysis that produced the p-value.

11. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using Fisher Exact, labeled as a superiority analysis, with p = 0.206. It does not provide a sponsor-reported effect estimate or confidence interval for that test. Separately, a simple unadjusted recalculation from the posted arm summaries gives a risk difference of 0.0 and confidence limits of 0.0 to 0.0, because the recorded counts are 21 of 21 and 22 of 22.

These results are not interchangeable. The recalculation is determined by the arm counts and totals as posted; the Fisher Exact p-value is the sponsor’s reported result. The registry record does not state which outcome assessment was used for that analysis, give the full contingency table, or explain why its reported p-value differs from the simple count-based comparison. It is therefore not possible to reproduce or reconcile the sponsor analysis from the information in the registry record.

The sponsor’s test should be reported as the sponsor’s own analysis, while the recalculation should be labeled as a simple summary-based calculation. Neither should be silently substituted for the other. The record does not provide sufficient detail to determine whether the mismatch reflects a different analysis population, outcome time, coding, or another cause; none of those explanations can be assumed.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, including the primary complete-resolution endpoint and the secondary Composite Severity Scale of Labial Adhesion Over Time. It also records 4 analyses. The primary endpoint has assessments at 3 weeks and 6 weeks, but the record does not identify which assessment time corresponds to the reported Fisher Exact result or describe how the two times were incorporated. It does not report a multiplicity adjustment, a hierarchy among analyses, or a prespecified rule for interpreting multiple tests. Whether and how multiplicity was addressed is not reported in the registry record.

The record also does not report a statistical analysis plan or specify the analysis population, such as whether the primary analysis included all randomized participants or another defined group. Participant disposition by arm, reasons for withdrawal, adherence, and the number of participants with missing endpoint assessments are not reported in the registry record. No imputation method, sensitivity analysis, or other missing-data approach is described. The posted arm counts match the recorded arm sizes, but that fact alone does not establish how missing observations, if any, were handled or how the counts correspond to the two follow-up assessments.

General explanation: multiple tests can increase the chance of a finding that appears statistically unusual by chance when each test is interpreted independently. A plan may address this through a hierarchy, adjustment, or other prespecified strategy. Missing-data choices can also affect estimates when outcome availability is related to participant characteristics or outcomes. Those are general statistical concerns, not claims that a particular problem occurred in this trial. The registry record does not contain enough information to evaluate either issue for this study.

13. 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 non-serious adverse event terms

The registry’s adverse-event record lists no serious adverse events for either group: 0 among 21 participants at risk in the Cetaphil group and 0 among 22 participants at risk in the estradiol cream 0.01% group. For other adverse events, it records 1 among 21 participants at risk in the Cetaphil group and 1 among 22 participants at risk in the estradiol cream 0.01% group. The registry lists no serious adverse-event terms.

These figures are descriptive counts in the posted record. They do not establish that no other events occurred outside the reported categories, and they do not quantify the likelihood of uncommon events with high precision. The registry does not provide event descriptions for the other adverse events, severity or relatedness assessments, timing, duration, or a fuller account of collection and reporting procedures. Death counts are not reported in the registry record.

General explanation: a zero count in a relatively small study does not prove that an event cannot occur; it means none was recorded in the reported group and category. Safety comparisons also depend on consistent definitions, follow-up, and ascertainment in both groups. The posted figures should therefore be read as reported counts, not as a complete characterization of safety.

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

The registry record documents a randomized comparison of Cetaphil and estradiol cream 0.01% for prepubertal labial adhesions, with complete resolution assessed at 3 weeks and 6 weeks. It reports arm counts of 21 of 21 and 22 of 22, respectively, and a Fisher Exact superiority-test result of p = 0.206. A simple unadjusted recalculation from the posted counts yields a risk difference of 0.0 with limits of 0.0 to 0.0. Because the registry does not explain how the reported test relates to those counts, the two summaries should remain distinct rather than being treated as mutually confirming evidence.

The record does not establish equivalence between the treatments. A failure to demonstrate a difference is not the same as demonstrating that differences are sufficiently small, and equivalence requires a prespecified margin and a suitable analysis. A margin is not reported in the registry record. Nor should the results be translated into a conclusion that one treatment works or does not work. The registry entries describe the registered study and its posted analyses; they do not provide a complete basis for a clinical recommendation.

The outcome timing and analysis population are not clearly linked to the reported test. The record also lacks sponsor-reported confidence limits, details on missing data, the statistical analysis plan, and results for the secondary outcome. These gaps restrict conclusions about the size and precision of any treatment contrast. The simple recalculated interval does not fill those gaps, particularly because it is based on the arm-level summaries and does not reconcile the reported p-value.

The adverse-event counts document no serious events in either group and one other event in each group, as recorded. These observations describe the reported experience but do not rule out unreported or uncommon events. Overall, the most defensible reading is descriptive: the registry records the trial design, outcome counts, one sponsor-reported test, and limited safety counts, while leaving important analytical and outcome-definition details unresolved.

15. Why This Trial Matters Statistically

This trial is statistically instructive because the displayed arm counts and the sponsor-reported test do not tell the same simple story. The posted counts are 21 of 21 and 22 of 22, and the straightforward risk-difference recalculation is 0.0 with limits of 0.0 to 0.0. The registry’s Fisher Exact analysis reports p = 0.206. The record does not explain how those quantities relate. Showing both rather than collapsing them into one conclusion illustrates why effect estimates, uncertainty intervals, and test results should be read together and tied to a clearly defined analysis.

The endpoint was scheduled at 3 weeks and 6 weeks, but the registry does not identify the time point used for the reported test. Repeated assessments can create distinct questions: status at a particular visit, change over time, or whether an outcome persists. General explanation: these questions may require different estimands and analysis methods. Naming the outcome and assessment schedule is useful, but readers also need to know which question the reported number answers.

The record also shows the difference between randomization as a design label and a fully described statistical analysis. It identifies randomization, parallel allocation, and quadruple masking, yet does not report sequence generation, masking roles, missing-data handling, analysis population, or a complete analysis plan. These omissions do not show that the trial was improperly conducted; they limit the reader’s ability to assess how design features and data were translated into the posted result.

Finally, the small set of posted safety counts can be stated plainly without being overinterpreted. A zero serious-event count is a record of observed reporting, not proof that risk is absent. Together, these features make the study useful for understanding how registry results require careful alignment of outcome definition, analysis, and interpretation.

16. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific limitations arise from the information not reported in the registry record. The primary endpoint is described as complete resolution at 3 weeks and 6 weeks, but the record does not define the assessment criteria or explain whether the reported count refers to one visit, both visits, or a combined rule. The relationship between the outcome timing and the reported Fisher Exact test is therefore unclear.

The reported arm summaries show all participants in each group counted as having the event, while the sponsor’s Fisher Exact analysis reports p = 0.206. The record does not provide the underlying analysis table, sponsor effect estimate, sponsor confidence interval, or enough methodological detail to reproduce the test. It is not possible to determine from the registry record why the two summaries differ. This limits interpretation of both the test and the simple recalculation.

The record does not report eligibility criteria in detail, participant flow, withdrawals, adherence, missing endpoint data, the analysis population, or a missing-data approach. It also does not provide the random-sequence method, allocation-concealment details, or the roles included in quadruple masking. These omissions limit assessment of the conduct and analysis without establishing that a particular bias occurred.

The secondary Composite Severity Scale of Labial Adhesion Over Time is listed, but its results and scoring details are not included in the registry record for interpretation. A statistical analysis plan, multiplicity strategy, and sample-size justification are not reported in the registry record. Safety reporting includes serious and other event counts but not event descriptions, relatedness, or detailed ascertainment procedures. The record is consequently informative about the registered design and some posted outcomes, but incomplete for a full evaluation of effect, precision, and safety.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Treatment of Prepubertal Labial Adhesions — NCT02218463.
• Registry record last updated 2025-04-23; status last verified 2025-04.
• Results first posted 2019-11-27.
• 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.

20. Record Summary

NCT02218463, titled Treatment of Prepubertal Labial Adhesions, is recorded as a completed randomized, parallel-group trial with quadruple masking. Enrollment was 43, and the sponsor was Children’s Mercy Hospital Kansas City. The study compared Cetaphil with estradiol cream 0.01%; both arm descriptions specify pea-sized topical application with lateral traction twice daily.

The primary outcome was complete resolution of labial adhesion, assessed at 3 weeks and 6 weeks. The registry posts counts of 21 of 21 for Cetaphil and 22 of 22 for estradiol cream 0.01%, alongside a Fisher Exact superiority-analysis result of p = 0.206. A simple unadjusted recalculation gives a risk difference of 0.0 with limits of 0.0 to 0.0; the record does not explain the difference between the displayed summaries and the reported test. Serious adverse-event counts were 0 in each group, and other adverse-event counts were 1 in each group. Further details on outcome timing, analysis methods, missing data, and precision are not reported in the registry record.