Comparison of Vaginal Laser Therapy to Vaginal Estrogen Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Vaginal Laser Therapy to Vaginal Estrogen Therapy (NCT02691936), a randomized na study. The primary outcome is Vaginal Dryness.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group trial with single masking, recorded as completed. The registry identifies The Cleveland Clinic as sponsor and describes the study as multicentered, prospective and single blinded. The trial compared CO2 fractionated vaginal laser therapy with conjugated estrogen cream in women with genitourinary syndrome of menopause. The phase is recorded as NA.

The registry records enrollment of 69. The posted primary-outcome groups contain 33.0 participants in the laser arm and 29.0 in the estrogen arm. The record does not explain the difference between the recorded enrollment and the group counts in the posted primary outcome, or give a participant-flow account. It does not report the randomization procedure, allocation concealment, the identity of the masked party, or the operational meaning of single masking.

The laser arm description specifies treatment at baseline, 6 weeks and 3 months. The estrogen arm description specifies conjugated estrogen cream at a dose of 0.5 g, equivalent to 0.625 mg of conjugated estrogen. The primary outcome was vaginal dryness at 6 months. Secondary outcomes included measures concerning vaginal atrophy or estrogenization, quality of life, vaginal maturation, vaginal wall elasticity, sexual function, urinary symptoms and treatment satisfaction. The registry record does not provide detailed schedules or measurement procedures for all secondary outcomes.

The recorded start was 2016-03 and primary completion was 2018-12. No protocol, recruitment history, treatment-adherence results, or reasons for discontinuation are reported in the registry record. Those omissions limit what can be concluded about how closely the planned treatment and follow-up were carried out.

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.

Population: Patients were included if they were menopausal with absence of menstruation for at least 12 months with reported presence of vaginal atrophy symptoms (subjective assessment of vaginal dryness greater than or equal to 7cm on visual analog scale (VAS).

6. Primary Endpoint

The registry lists the primary outcome as Vaginal Dryness, measured over 6 months.

The primary endpoint was vaginal dryness assessed at 6 months on a Visual Analog Scale. The scale runs from 0, its minimum, to 10, its maximum. The posted measure is described as the mean difference before and after treatment, rather than a single follow-up score. The registry description says that a higher mean difference signifies a greater decrease in dryness and therefore a better outcome.

Change from before treatment can help describe whether scores shifted during follow-up while accounting for each participant's starting measurement. However, a change score is not by itself a comparison of treatments: the difference between the groups' changes must be estimated and its uncertainty assessed to answer a comparative question. The registry reports a mean difference for each arm but does not report a direct between-group estimate or test for this primary outcome.

The posted values are -5.48 for the laser group and -5.76 for the estrogen group, with ranges of -8.16 to -2.8 and -8.24 to -3.28, respectively. The record labels the dispersion as full range. These ranges therefore should not be read as confidence intervals. Since the description's interpretation of “higher” mean differences is not reconciled with the negative values or a stated subtraction convention, the sign alone does not establish how the change should be read. The outcome is relevant to the question of symptom change, but the registry record does not provide enough detail to resolve that coding ambiguity or quantify the primary between-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a group mean difference describe?

In general, a mean difference summarizes the average change in a measured outcome across participants in a group. A change measure can be useful when the scientific question concerns movement from a starting value, but its interpretation depends on the order of subtraction and the direction of the scale. Here, the registry says that a higher mean difference indicates a greater reduction in dryness, while posting negative values. Since the record does not clarify the calculation convention, the sign and verbal description cannot be reconciled from the registry record alone.

A group-specific change is also not the same as a treatment contrast. To compare randomized groups, an analysis would ordinarily estimate the difference between their outcomes or changes, and describe uncertainty around that estimate. A test or interval for that contrast addresses whether the observed separation is distinguishable from sampling variability under the chosen analysis. The registry does not report a direct contrast for the primary dryness endpoint. It is therefore not appropriate to infer a primary between-group effect by comparing the two reported means informally.

What do the reported ranges mean?

The primary endpoint is labelled with “Full Range” as its dispersion measure. In general, a range describes the lowest and highest values in the data used for that summary. It is not a confidence interval for a mean or a treatment contrast. A confidence interval instead describes uncertainty in an estimated quantity under an inferential procedure. Although the posted ranges overlap, that observation does not supply a test of the difference between groups or establish equivalence.

The interval reported for the secondary risk difference has a different role from the primary full ranges. For that secondary comparison, the posted risk difference is 0.101, with an interval from -0.146 to 0.349. The interval includes zero, the value corresponding to no risk difference. In general, an interval spanning zero indicates that the data and calculation are compatible with no difference as well as with values on either side, at the interval's stated confidence level. The registry record does not state the confidence level or the precise interval method, so neither should be inferred.

How should the secondary risk difference and p-value be read?

A risk difference expresses a contrast between the proportions with an outcome in two groups. The posted comparison is for estrogen relative to laser. The point estimate is 0.101, and the unadjusted p-value is 0.425. 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. A p-value by itself does not establish no effect; in this case, the interval also indicates substantial uncertainty in the direction and magnitude of the comparison.

The comparison is identified as unadjusted. In general, an unadjusted analysis estimates the contrast without accounting for other variables in a model. Random allocation is intended to support fair comparison, but the registry record does not report a detailed statistical model, covariate adjustment, or the analysis population. The posted estimate should therefore be read as the specific unadjusted calculation, not as a fully documented sponsor analysis.

What are the planning illustrations for?

In general, a sample-size calculation asks how many participants would be needed to detect a specified effect under stated assumptions. It is a planning exercise, not a description of what the trial observed and not a measure of observed power. The record's planning assumptions state a two-sided significance level of 0.05, equal allocation, a normal approximation and an effect defined as a stated fraction of the observed effect. These assumptions are described as an illustration based on the observed secondary effect, not as the trial's original design justification.

For planning for 100% of the observed effect, the illustration gives 379 participants per arm for 80% power and 507 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 677 participants per arm for 80% power and 906 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 1,527 participants per arm for 80% power and 2,043 participants per arm for 90% power. These are hypothetical planning quantities under the stated assumptions. They are not observed participant counts, and they do not show that the trial had any particular power.

In general, planning for a smaller effect requires more information, because a smaller separation is harder to distinguish from random variation. Such illustrations are sensitive to the assumptions and to the observed effect used as their starting point. They do not establish the effect that a future study should target, and they do not replace a protocol-based sample-size justification. The trial's own sample-size justification is not reported in the registry record.

Why does over-dispersion matter in general?

For count or binary outcomes, a statistical model may make assumptions about how much variation is expected. In general, over-dispersion means that the observed variability exceeds what a chosen model assumes. If not accounted for, uncertainty estimates can be too narrow and tests can be misleading. The registry record does not identify an over-dispersion assessment for these outcomes, so this is a general consideration, not a claim about this trial.

More broadly, statistical interpretation depends on prespecified outcomes, analysis methods, missing-data handling and a clear definition of who was included. Those details are not fully reported in the registry record. The posted values can be described on their own terms, but the absent methods limit independent assessment of assumptions and analytic choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and seven secondary outcomes. In general, examining multiple outcomes increases the chance that at least one result may appear unusual even when there is no corresponding effect. A prespecified hierarchy, adjustment procedure or clear exploratory framing can help readers understand how to interpret multiple tests. The registry record does not report a multiplicity strategy, and no sponsor-reported analyses are listed for the secondary outcomes. The posted secondary comparison is unadjusted, so it should be interpreted cautiously and not as a confirmatory result.

Missing-data handling is not reported in the registry record. The record does not describe the amount or pattern of missing outcome data, the method used to handle missing observations, or whether an imputation procedure was used. It also does not explain whether all randomized participants were included in each outcome analysis. The recorded enrollment is 69, while the primary outcome groups have posted counts of 33.0 and 29.0; the record does not explain the difference or provide a flow of participants through follow-up and analysis.

The analysis population is not reported in sufficient detail to determine whether the results follow an intention-to-treat approach, a per-protocol approach, or another rule. In general, intention-to-treat analysis retains participants in their assigned groups regardless of treatment received, while other analysis populations may apply eligibility or adherence rules. Those choices can affect interpretation, particularly if follow-up or treatment exposure differs by group. No such differences should be assumed.

The record does not report interim analyses, stopping rules, protocol deviations, or the prespecified statistical plan. It also does not report a sample-size justification for the trial's original design. These omissions do not show that particular procedures were or were not used; they mean that the registry record does not document them. Consequently, readers cannot assess from the registry alone whether analytic decisions were planned before outcomes were examined or how incomplete observations were addressed.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures show 0 affected participants in the CO2 fractionated vaginal laser group and 0 in the conjugated estrogen group. The corresponding groups at risk are 33 and 29, respectively. The record also reports 0 deaths in each group. These are the figures recorded for serious adverse events and deaths during the registry's reported safety period; the record does not give a more detailed period or event narrative.

For other adverse events, the registry reports 5 affected participants in each group, with 33 and 29 participants at risk, respectively. The record does not identify the event terms in these counts or provide severity, timing, duration, or treatment-relatedness details. The counts should therefore be read as the registry's reported affected-participant summaries, not as a description of specific event types.

A zero count in a trial does not establish that an event cannot occur, and these group counts alone do not provide a precise comparison of safety. In general, safety interpretation depends on event definitions, observation time, completeness of reporting and the size and composition of the groups. The registry record does not provide enough detail to assess those elements fully. These figures describe what was posted; they are not a basis for medical advice.

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

The registry record documents a randomized comparison of vaginal laser therapy and conjugated estrogen cream, with vaginal dryness assessed at 6 months as the primary outcome. The posted group-specific mean differences and ranges describe the reported summaries. They do not provide the direct between-group estimate needed to quantify a primary treatment contrast, and the negative values are not reconciled with the description that a higher mean difference signifies a greater reduction in dryness.

The secondary comparison for vaginal wall elasticity is explicitly unadjusted. Its point estimate and interval express uncertainty, with the interval including no risk difference and values in either direction. This is not proof that treatments are the same. Nor does it show that any difference would be clinically meaningful. The record does not state a threshold for a meaningful change in dryness or a meaningful between-group difference.

In general, a randomized design can support causal comparisons when allocation, follow-up and analysis are conducted and reported appropriately. The registry record does not document enough about randomization procedures, analysis populations, missing data, adherence or the statistical plan to evaluate these elements fully. The results should therefore be interpreted as registry-posted outcome summaries rather than as a complete account of the trial's comparative analysis.

The posted information does not establish that either treatment is superior, equivalent or ineffective. It also does not establish a broad conclusion across symptoms, examination measures, function, urinary outcomes or satisfaction. Such conclusions would require interpretable between-group analyses, adequate precision, and transparent reporting of outcome definitions and missing data. The safety figures are likewise limited to the counts posted and do not describe the types or timing of adverse events.

Thus, the most defensible reading is narrow: the record reports particular outcome summaries at the stated follow-up, but does not provide sufficient primary comparative inference to determine the size, direction or precision of the difference in vaginal dryness between groups. Any wider interpretation should be restrained by the missing statistical and participant-flow details.

13. Why This Trial Matters Statistically

This trial raises a central biostatistical distinction: reporting a change within each randomized group is not the same as estimating the difference between randomized groups. The clinical question is comparative, but the primary result is posted as two separate mean differences. Without a direct contrast and its uncertainty, readers cannot determine how precisely the primary endpoint distinguishes the treatments.

It also illustrates why measurement conventions matter. The registry describes higher mean differences as indicating greater reductions in dryness, yet the posted values are negative and the calculation order is not stated. A numerical estimate can be difficult to interpret when its sign is not linked unambiguously to the scale and subtraction convention. Clear outcome definitions and analysis descriptions are therefore part of the evidence, not merely technical detail.

The secondary result illustrates a related point about uncertainty. An unadjusted point estimate can appear directional, but an interval spanning zero may remain compatible with a range of possible contrasts. That uncertainty is particularly relevant when several secondary outcomes are listed and no multiplicity strategy is reported. A single secondary p-value should not be elevated above the broader context of the analysis.

Finally, planning calculations based on an observed effect are not the same as the original design justification or observed power. They can illustrate how required sample sizes change under different assumed effects, but their usefulness depends on assumptions and on the stability of the effect used. The record explicitly frames the calculations as planning illustrations, while the trial's own design justification is not reported.

These distinctions help readers separate descriptive summaries, comparative inference, planning assumptions and safety counts. For this record, that separation is important because the primary comparison and several supporting analysis details are not reported.

14. 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 limitations specific to this registry record restrict interpretation. The primary outcome description gives a favorable meaning to a higher mean difference, while both posted group values are negative. The record does not state the subtraction order or explain the sign convention. This leaves ambiguity about the direction of the primary change, beyond the numerical summaries themselves.

The primary endpoint is reported by group, with full ranges, but no direct between-group estimate, confidence interval or test is reported. Full ranges describe observed extremes and do not quantify uncertainty in a treatment contrast. The registry also does not give a threshold for clinical importance, so the magnitude of any potential difference cannot be judged against a stated meaningful-change criterion.

There is no detailed participant-flow account. Enrollment is recorded as 69, while the posted primary outcome group counts are 33.0 and 29.0. Reasons for this difference, follow-up completeness, exclusions and analysis populations are not reported. The record also does not describe missing-data methods, treatment adherence, protocol deviations, the randomization procedure, allocation concealment or the precise masking arrangements.

The listed secondary domains are broad, but a complete set of comparative results and a multiplicity approach are not reported. The one posted unadjusted secondary comparison is not a substitute for a complete analysis across outcomes. The record does not provide the statistical analysis plan, the trial's sample-size justification, or interim-analysis information. These omissions limit reproducibility and make it difficult to determine how prespecified the reported analyses were.

Safety reporting is also limited: event types, timing, severity details and relatedness are not described. These limitations concern reporting in the registry record; they do not demonstrate that particular procedures or analyses were absent from the underlying study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of Vaginal Laser Therapy to Vaginal Estrogen Therapy — NCT02691936.
• Registry record last updated 2019-10-30; status last verified 2019-10.
• Results first posted 2019-10-17.
• 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.

18. Record Summary

NCT02691936 is a completed, randomized, single-masked, parallel-group clinical trial sponsored by The Cleveland Clinic. The record describes a multicentered comparison of CO2 fractionated vaginal laser therapy and conjugated estrogen cream for women with genitourinary syndrome of menopause. Recorded enrollment is 69, and the phase is listed as NA.

The primary outcome was vaginal dryness measured on a Visual Analog Scale at 6 months, reported as a mean difference before and after treatment. Group-specific values and full ranges are posted, but no direct primary between-group analysis is reported. The description of the direction of improvement is not reconciled with the negative posted values.

Seven secondary outcomes are listed. The posted vaginal wall elasticity comparison is unadjusted and imprecise. Serious adverse event and death counts are reported as 0 in each group; other adverse events are reported for 5 participants in each group. Details about the event types, missing data, analysis populations, multiplicity and statistical plan are not reported in the registry record.