The CO2RE® System for Vulvar Lichen Sclerosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The CO2RE® System for Vulvar Lichen Sclerosus (NCT04148651), a na na study. The primary outcome is Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators.

2. Clinical Question

The clinical signs were scored individually, including features such as loss of elasticity, sclerosis, whitening, fissures, erosions and ulcerations. The endpoint combines the grades for signs present at baseline into an average severity score for each subject. The record says that a lower average score means a better outcome. This is a within-group question about change over time, not a comparison of treatment with an untreated or alternative-treatment group.

The registry also identifies secondary outcomes concerning sexual function on the Female Sexual Function Index (FSFI), subject satisfaction, and treatment-associated pain. Their presence in the outcome list does not establish that results were reported. Numerical findings for these outcomes are not reported in the registry record.

3. Trial Design

The registry lists a completed, single-group clinical study of the CO2RE® System for vulvar lichen sclerosus. Enrollment was 14. The listed study dates are 2018-07-11 for the start and 2020-07-30 for primary completion. The study phase is recorded as NA, allocation as NA, and masking as none. Candela Corporation is named as the sponsor.

All eligible subjects were to receive treatment to the vulva with a fractional CO2 laser, with up to 5 treatments at 4±1-week intervals. The registry describes follow-up for clinical signs through 12 months after the final treatment. The primary endpoint schedule is baseline and 3, 6 and 12 months after the last treatment. This design can describe observations over time in treated participants, but it does not include a randomized comparison group in the registry description.

The primary outcome is an investigator-assessed average severity grade based on clinical signs that were present at baseline. The record also lists secondary outcomes for change in FSFI sexual-function scores at 3 and 6 months after the final treatment, satisfaction at the 12-month follow-up, and treatment-associated pain. The registry lists 5 outcome measures, but does not report numerical results for these outcomes in the information.

Although the study status is completed, completion status alone does not supply an estimate of treatment-associated change or its precision. The registry record lists 0 analyses. A statistical analysis plan, sample-size justification, interim-analysis plan and details of any control procedures are not reported in the registry record. The study's single-group structure also means that changes over time cannot by themselves separate treatment-associated change from other explanations, such as natural variation or measurement effects.

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: Although 14 subjects enrolled, 1 subject was withdrawn from the study due to a protocol violation and 1 subject was found to be not eligible prior to her first treatment. Therefore, 12 subjects are included in this analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: At Baseline, 12 subjects had 96 clinical signs present (score \>0). One subject missed the 12-month follow-up, one subject missed the 3- and 12-month follow-ups and one subject missed the 6-month follow-up. Hence, at 3- and 6-month follow-up visits 11 subjects were assessed (with 89 clinical signs averaged for each visit) and at the 12-month follow-up visit 10 subjects were assessed (with 79 clinical signs averaged).

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: Although 14 subjects enrolled, 1 subject was withdrawn from the study due to a protocol violation and 1 subject was found to be not eligible prior to her first treatment. Both are not included in the Results analysis.

6. Primary Endpoint

The registry lists the primary outcome as Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators, measured over At Baseline, 3, 6 and 12 months after the final treatment.

The primary endpoint is the average severity grade for VLS clinical signs that were present at baseline. Investigators assessed each sign separately on a 4-point scale: 0 means not present, 1 mild, 2 moderate and 3 severe. The signs listed include loss of elasticity, sclerosis, lichenification, whitening, parchment-like skin, fissures, extent of disease, erosions, ulcerations, hyperkeratosis, excoriation and telangiectasia.

For each subject, the average is formed from the grades for the signs present at baseline. The registry describes assessing this average at baseline and at 3, 6 and 12 months after the final treatment. It states that a lower average score means a better outcome. Focusing on signs present at baseline provides a way to track the severity of the individual's initial set of signs over time, rather than treating newly absent baseline signs as if they had never been part of the assessment.

An average can make a set of sign-specific grades easier to summarize, but it also compresses information: different patterns of change among individual signs can yield similar averages. The registry record does not report numerical means, standard deviations, changes from baseline or confidence intervals for the endpoint. Thus, the measure's definition is available, but the magnitude and precision of any observed change are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines a continuous primary measure summarized as a mean and standard deviation. The outcome is an average severity grade assembled from investigator ratings of VLS clinical signs present at baseline. Each sign is scored on a 4-point scale, from not present through severe. The stated endpoint visits are baseline and 3, 6 and 12 months after the final treatment. The registry says that a lower average score means a better outcome.

What does a mean describe?

In general, a mean is a way to summarize the central level of a set of measurements. For this endpoint, the subject-level average combines grades across the signs present at baseline. A group mean would then summarize the subject-level values at a visit. It can be useful for describing a broad pattern, but it does not show whether every sign changed in the same way or whether every participant followed the group pattern.

Because the endpoint averages ordinal grades, its interpretation depends on the registry's stated scoring and averaging procedure. The grades express ordered severity categories, and the average gives a compact summary across signs. Such a summary may conceal clinically distinct profiles: one participant could have improvement in some signs and persistence in others, while another could have a different mix of changes. The registry does not report sign-specific results that would allow those patterns to be examined.

What does the standard deviation describe?

In general, a standard deviation describes how dispersed measurements are around their mean. A small standard deviation indicates that values are relatively clustered; a larger one indicates more spread. It is not the same as a confidence interval and is not, by itself, a measure of uncertainty in the group mean. The registry identifies standard deviation as the dispersion measure for the primary endpoint, but numerical standard deviations are not reported in the registry record.

What would a within-group comparison show?

In general, comparing a group's measurements across visits can describe change over time. If the same participants contribute at multiple visits, their observations are related rather than independent. An analysis of repeated measurements can account for that relationship, but the registry record does not report which statistical model or test was used. It does not report whether the analysis used individual visit values, change from baseline, or another approach. With no randomized comparison group listed, a within-group change would not isolate the effect of treatment from other time-related influences.

The registry lists the primary outcome's visit schedule and the subject counts available at some follow-ups, but it does not give the numerical means or any inferential results. A p-value, when reported, addresses compatibility between data and a specified statistical model under a null hypothesis; it does not measure the size or importance of an effect. A confidence interval, in general, gives a range of values compatible with the data and the method's assumptions. Neither p-values nor confidence intervals for the primary endpoint are reported in the registry record.

What can planning illustrations tell a reader?

In general, sample-size planning asks how many participants would be needed to detect a chosen effect under specified assumptions. The planning description for this record refers to a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; it also describes planning for a stated fraction of an observed effect. Such assumptions describe an illustrative calculation, not the study's observed result or its design. The trial itself is listed as single-group, rather than as a two-arm comparison.

Any planning illustration based on an observed effect depends on the effect estimate used. The numerical effect and resulting planning counts are not reported in the registry record. These illustrations should not be interpreted as observed power, as evidence that the study detected an effect, or as proof that the actual design had a particular probability of success. A planning calculation is conditional on its assumptions and target; it does not replace reporting the outcome estimate and its uncertainty.

What statistical plan is documented?

The registry lists 0 analyses. A detailed statistical analysis plan, the exact inferential procedure for the primary endpoint, model assumptions, any covariate adjustment, and rules for choosing among analyses are not reported in the registry record. The endpoint description establishes how the average severity grade is defined, but a definition of an outcome is not a complete statistical analysis plan. Without reported analysis methods and results, readers cannot assess whether the planned method was followed or how robust the findings might be to different reasonable analytic choices.

General statistical interpretation depends on the link between the measure, the analysis population, the missing-data approach and the uncertainty estimate. The registry describes some missing visits and the intended endpoint, but does not report a complete account of those analysis decisions. Accordingly, the methods that can be described are limited to the scale, averaging rule, summary statistic and scheduled assessments in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary clinical-sign endpoint and secondary outcomes for FSFI sexual function, satisfaction and treatment-associated pain. When several outcomes or time points are examined, there are multiple opportunities to observe a result that appears noteworthy by chance. Statistical approaches can address this issue by prespecifying a primary comparison, adjusting for multiple testing, or clearly identifying analyses as exploratory. Whether any such approach was used is not reported in the registry record.

The primary endpoint is scheduled at baseline and at 3, 6 and 12 months after the final treatment. The record does not report whether one follow-up was designated as the principal inferential comparison, whether all visits were analyzed together, or whether multiplicity was otherwise addressed. The registry lists 0 analyses, so no inferential results or multiplicity adjustments can be evaluated from the record.

Missing observations are documented: 12 subjects had baseline clinical signs present; 11 subjects were assessed at the 3- and 6-month visits. One subject missed the 12-month visit, one missed the 3- and 12-month visits, and one missed the 6-month visit. The record does not report why visits were missed, whether the missingness was related to outcomes, or what method was used to handle missing measurements. It also does not report whether an analysis used all available observations, a restricted set of participants, imputation, or another strategy.

General statistical practice distinguishes the population intended for analysis from the people with observations available at each visit. The registry record does not define an analysis population or describe exclusions after enrollment. It is therefore not possible to determine whether reported estimates, if any, would represent all enrolled participants or a subset. Missing-data assumptions can influence interpretation, especially when follow-up availability differs across visits; the record does not provide enough information to assess their impact.

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.

The posted safety figures list 12 subjects at risk for serious adverse events and 0 affected. For other adverse events, the record likewise lists 12 subjects at risk and 0 affected. Deaths are listed as 0. These are counts in the registry record, not estimates of risk for a broader population.

The figures should be read with their denominators in view: the record gives 12 subjects at risk in each category, while total enrollment is 14. The registry does not explain the difference between enrollment and the number at risk in the posted safety data. It is not appropriate to assume that all enrolled participants contributed to the safety counts or to infer reasons for the difference.

The record lists no top serious adverse-event terms. The posted counts do not establish that no symptoms or other events occurred; they indicate that the listed serious and other adverse-event categories had 0 affected among the 12 subjects at risk. Detailed event definitions, collection procedures, severity classifications, follow-up coverage and reasons for any unavailable safety observations are not reported in the registry record. The counts therefore describe the posted safety information but do not answer questions beyond those categories and participants.

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

The study record describes a prospective clinical question in participants with vulvar lichen sclerosus: how investigator-rated severity of signs present at baseline was assessed over follow-up after treatment with the CO2RE® System. It provides the outcome's scoring rule, planned visit schedule, treatment regimen and some visit-availability information. These details help clarify what the primary measure was intended to represent.

The registry does not report numerical primary outcome results. As a result, the direction and magnitude of any change in average severity cannot be determined from the posted information, and its precision cannot be assessed. The stated rule that lower scores mean better outcomes defines how a score would be interpreted; it is not evidence that scores decreased. The secondary outcomes are listed, but their numerical findings are also not reported in the registry record.

The single-group design is important for interpreting any change that might be reported elsewhere. Without a concurrent comparison group, an observed difference between baseline and follow-up would describe a change over time among assessed participants, not a randomized estimate of the treatment's effect. Changes unrelated to treatment, variation in measurement, and the pattern of who returned for follow-up could also matter. The record does not report analyses that address these issues.

The safety counts show 0 serious events and 0 other events among 12 subjects at risk in each category, with 0 deaths listed. They should not be generalized beyond the registry's stated counts, and they do not substitute for detailed safety reporting. The record does not provide the event-level information or assessment procedures needed to characterize safety more fully.

In short, the registry supports a description of what was planned and which limited outcome and safety counts were posted. It does not support a quantitative conclusion about primary endpoint change, a statistical-significance claim, a precise estimate, or a causal treatment-effect conclusion. Those conclusions require reported estimates, uncertainty measures and analysis details, which are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between defining an endpoint and reporting evidence about that endpoint. The registry gives a detailed description of how investigators rated clinical signs, which signs contributed to the average, and when assessments were scheduled. Yet numerical outcome estimates and analyses are not reported in the registry record. A carefully defined measure is necessary for interpretation, but it cannot show the size, direction or precision of a result without the corresponding data summaries.

The study also makes the role of design clear. A single-group follow-up can describe how scores change within participants who are assessed over time. It cannot, on its own, provide a randomized contrast against another treatment or a control condition. That distinction matters because a change over time and a causal effect are different statistical quantities. Reporting should make the design and the limits of its comparisons clear.

Follow-up availability is another practical statistical issue. The record identifies missed visits and varying numbers assessed at follow-up. These details matter because analyses can be affected when the participants observed at one time point differ from those observed at another. Clear reporting of the analysis population and missing-data methods would help readers judge how much the available observations represent the enrolled group.

Finally, multiple outcomes and visits call for transparent reporting of which results were prioritized and how analyses were selected. The registry lists several outcomes but no analyses. Without results or an analysis plan, readers cannot assess multiplicity, precision or the relationship between prespecified questions and reported findings. The record is therefore informative about endpoint construction and study structure, while leaving the statistical evidence for the outcome questions unreported.

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 record constrain interpretation. First, it is a single-group study with no randomized allocation or masking. There is no listed control group against which to distinguish observed changes over time from other influences. The registry record does not report methods that would supply a randomized comparison.

Second, the primary endpoint is based on investigator ratings of multiple clinical signs and then averages grades for signs present at baseline. The record describes the scale and averaging rule but does not report numerical endpoint results, sign-level results, or information about consistency of ratings between or within investigators. The effect of rating variability cannot therefore be assessed from the registry record.

Third, follow-up was incomplete for some participants. The record reports missed assessments at 3, 6 and 12 months and fewer subjects assessed at the 3- and 6-month visits than the number with baseline signs. Reasons for missed visits and the statistical handling of missing observations are not reported in the registry record. Those omissions leave uncertainty about how follow-up availability may affect any estimate.

Fourth, the registry lists 5 outcome measures but 0 analyses. Numerical results, confidence intervals, p-values, analysis populations, multiplicity procedures and a statistical analysis plan are not reported in the registry record. Thus, neither the primary outcome's precision nor the treatment of secondary outcomes can be evaluated.

Finally, the safety figures concern 12 subjects at risk, whereas enrollment is 14. The record does not explain that difference or provide detailed event-level information. The posted safety counts should be interpreted within their stated scope and not as a complete characterization of every possible event or every enrolled participant.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The CO2RE® System for Vulvar Lichen Sclerosus — NCT04148651.
• Registry record last updated 2022-03-22; status last verified 2022-02.
• Results first posted 2021-01-22.
• 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

NCT04148651 is a completed, single-group study of the CO2RE® System for vulvar lichen sclerosus, sponsored by Candela Corporation. Enrollment was 14. The registry lists no masking, allocation as NA, and phase as NA. The treatment description specifies up to 5 fractional CO2 laser treatments at 4±1-week intervals.

The primary endpoint is the average severity grade for clinical signs present at baseline, assessed at baseline and at 3, 6 and 12 months after the final treatment. The record describes the 4-point scale and states that lower average scores mean better outcomes. It reports missed follow-up visits and states that 11 subjects were assessed at the 3- and 6-month visits.

The registry lists 5 outcome measures and 0 analyses. Numerical primary and secondary outcome results, a statistical analysis plan, and missing-data methods are not reported in the registry record. Safety figures list 12 subjects at risk, 0 serious events, 0 other events and 0 deaths.