Performance and Safety of Restylane Lidocaine for Treatment of Depressed Facial Acne Scars: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Performance and Safety of Restylane Lidocaine for Treatment of Depressed Facial Acne Scars (NCT03127384), a randomized phase 4 study. The primary outcome is Percentage of Participants With Lower Scar Severity in the Treated Cheek Compared to the Untreated Cheek.

2. Clinical Question

The primary question is comparative and directional: it concerns whether scar severity was assessed as lower on the treated side than on the untreated side. It is not a question about change from a baseline score alone, nor does the registry description define a minimum difference that would count as meaningful.

The record also lists the percentage of participants improved on the Global Aesthetic Improvement Scale as a secondary outcome. That is a separate outcome measure; its definition and result are not reported in the available record details. The primary endpoint’s stated assessment time is Month 3. No other primary assessment time is listed.

The study is described as randomized and evaluator-blind. Those design features are relevant to how the comparison was intended to be made, but the registry record does not describe the randomization procedure or explain exactly how the evaluator’s blinding was maintained. It also does not state how participants with equal scar severity on both cheeks were classified for the primary measure. Those details matter for a fully reproducible interpretation of the clinical question.

3. Trial Design

The registry describes a Phase 4, randomized, single-masked, parallel-model study comparing Restylane Lidocaine with no-treatment control. The official title calls it an evaluator-blind comparative study. The treatment arm is described as intradermal injection of Restylane Lidocaine; the control arm is described as no treatment. The group title uses the wording “Split-face: Treatment/No-treatment Control.” Together, these descriptions indicate that the intended comparison involved treated and untreated cheeks, while the formal model field is recorded as parallel.

The difference between the split-face group title and the parallel-model label is not explained in the registry record. Nor does the record specify how cheeks were assigned, whether assignment was randomized within participants, or how any treatment-side allocation was concealed. These omissions limit how precisely the allocation structure can be reconstructed from the entry alone.

The stated enrollment is 49. The record gives a start date of 2017-04-20 and a primary completion date of 2018-02-15, and lists the study status as completed. Galderma R&D is identified as sponsor. The condition field lists Healthy Volunteers, while the title and study purpose concern depressed facial acne scars; the record does not explain this labeling.

The primary endpoint is the percentage of participants with lower scar severity in the treated cheek compared with the untreated cheek at Month 3. The description says scar severity was assessed by a blinded evaluator. A secondary outcome concerns improvement on the Global Aesthetic Improvement Scale. The registry lists two outcome measures but does not provide the definitions and results for both in the record details available for this analysis.

The registry record does not report the detailed protocol, eligibility criteria, treatment schedule, evaluator training, or the methods used to implement masking. It also does not describe participant flow, withdrawals, or the number of participants assessed at Month 3. These details should not be inferred from the enrollment figure or the completed status.

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 Percentage of Participants With Lower Scar Severity in the Treated Cheek Compared to the Untreated Cheek, measured over Month 3.

The primary endpoint is a percentage: the proportion of participants whose treated cheek was assessed as having lower scar severity than the untreated cheek at Month 3. The registry says the assessment was made by a blinded evaluator. The endpoint therefore expresses a within-participant, side-to-side comparison rather than a mean score difference between separate treatment groups.

In general, a binary endpoint reduces each participant’s assessment to whether a defined condition was met. Reporting a percentage can make the frequency of that condition easier to interpret than a raw count alone, provided the numerator and denominator and the classification rules are clear. Here, the registry names the condition being counted but does not give the observed percentage, confidence interval, analyzed denominator, or the rule for handling equal severity or unavailable assessments.

Comparing cheeks within a participant can account for characteristics shared by both sides, such as features that do not vary from one cheek to the other. That is a general design consideration, not evidence about the trial’s results. A split-face comparison also requires clear handling of side assignment, evaluator blinding, and within-person dependence. The registry description does not provide enough methodological detail to evaluate those aspects.

The endpoint is used to address the study’s stated comparative question at a specified follow-up time. It does not, by itself, describe the size of any severity difference, whether a difference is clinically important, or whether the result is precise. Those judgments require the actual estimate, its uncertainty, and a clear account of how the endpoint was measured. The result and confidence interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are converted into estimates and how much uncertainty is attached to those estimates. The registry entry gives some design and endpoint information, but it does not report the primary analysis method or an analysis result. The points below explain relevant concepts in general and distinguish them from methods documented for this study.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified according to whether the specified condition occurred. A percentage expresses the number meeting that condition relative to the number assessed in the analysis. For this endpoint, the condition is lower scar severity in the treated cheek than in the untreated cheek at Month 3. The registry record does not report the observed percentage, the denominator used, or the classification details for ties or missing assessments. Without those details, the result cannot be independently reconstructed.

A percentage does not describe how large the difference in scar severity was for each participant. It counts whether the specified directional comparison was met. Two studies could have the same percentage while differing in the size of the cheek-to-cheek differences. This is a general feature of binary outcomes, not a finding about this trial.

Why does the confidence interval matter?

A confidence interval gives a range of values compatible with the observed data under the statistical method and its assumptions. It is a measure of estimation uncertainty, not a guarantee that the true value lies within a particular realized interval. Its width depends on factors including the amount of information in the data and the variability represented by the analysis.

The endpoint description specifies a 95% confidence interval as its dispersion measure, but the registry record does not report the interval itself. Without the estimate and interval, neither the direction and size of the observed result nor its precision can be assessed. A confidence interval also does not determine whether an effect is important to patients; that requires a meaningful clinical threshold, which is not reported.

What is distinctive about a split-face comparison?

In general, a split-face design compares two sides within the same participant. The two observations from a participant are related rather than independent. An analysis should reflect that pairing or within-person dependence. Treating related observations as if they came from unrelated participants can misrepresent uncertainty.

The registry group title describes a split-face comparison, but the model field records a parallel design. The entry does not explain this difference or report an analysis method that clarifies how the comparison was handled. It also does not state how sides were allocated or how the blinded evaluator assessed them. Consequently, the appropriate statistical method cannot be identified from the record alone.

What do the planning assumptions mean?

In general, a sample-size planning calculation estimates the amount of information that may be needed to detect a chosen effect under specified assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It distinguishes participant counts per arm from total event counts for time-to-event calculations.

Such planning values are illustrations, not evidence about how many participants were needed under the trial’s original protocol, and not a measure of the probability that the completed trial detected an effect. They are not “observed power.” The registry record does not report the trial’s own sample-size justification. No numerical planning outputs or effect fractions are stated in the record details, so none can be interpreted.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability exceeds what a model assumes. If a model understates variability, its uncertainty estimates may be too small. That concern can arise in some types of count or clustered data, but the primary outcome in this record is described as a percentage of participants, and the registry does not identify a model for it. There is no basis for asserting that over-dispersion was present or that a particular adjustment was used.

Overall, the record supports an explanation of the endpoint and some design considerations, but not an evaluation of the analysis. The test, confidence-interval method, handling of missing observations, and analysis population are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Split-face: Treatment/No-treatment Control")
n      <- c(47)
events <- c(38)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Split-face: Treatment/No-treatment Control  47  38  80.9  66.7  90.9  67.5  89.6  67.4  89.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary percentage with lower scar severity in the treated cheek than in the untreated cheek, and a secondary outcome concerning improvement on the Global Aesthetic Improvement Scale. Considering multiple outcomes can raise multiplicity concerns. In general, the more statistical comparisons made, the greater the chance of a seemingly notable finding arising by chance if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether any adjustment was applied.

The record does not report an analysis population for either outcome. It does not identify whether analyses included all randomized participants, only participants who completed follow-up, or another defined group. The number assessed for the primary outcome is also not reported. Enrollment of 49 should not be treated as proof that all enrolled participants were analyzed.

Missing-data methods are not reported in the registry record. There is no description of how unavailable Month 3 assessments were handled, whether reasons for missingness were recorded, or whether any sensitivity analyses were conducted. In general, missing outcome data can affect both the estimate and its uncertainty, particularly if the likelihood of missingness is related to the outcome. Without the missingness pattern and analysis method, that issue cannot be evaluated for this study.

The registry lists no analysis entries. Interim analyses, stopping rules, and other details of the statistical plan are not reported in the registry record. No particular approach should be assumed.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: worsening of spinal disc herniation (2.0%).

The serious adverse event group is titled “Split-face: Treatment/No-treatment Control.” The record lists 49 at risk for the treatment side and 49 at risk for the no-treatment control side. It reports 1 affected for the serious adverse event measure in the treatment group and 9 affected in the control group. Deaths are recorded as 0. The record also lists “Worsening of spinal disc herniation” among the top serious terms, at 2.0%.

These are descriptive figures as recorded; they do not establish that an event was caused by treatment or by control. The registry entries do not explain how serious events were attributed in a split-face study, whether counts refer to participants or event occurrences for every field, or how the listed term relates to the group-level figures. No statistical comparison or uncertainty interval for these safety counts is reported.

At-risk figures are not necessarily the denominator for every safety interpretation unless the record defines them that way. The available details do not provide further exposure information, event timing, severity classifications beyond seriousness, or the methods used to collect and assess events. The figures should therefore be read as registry-reported safety counts, not as a causal comparison or a complete safety profile.

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

The registry record describes a randomized, evaluator-blind study comparing intradermal Restylane Lidocaine with no treatment for depressed facial acne scars. Its primary question is whether, at Month 3, a participant’s treated cheek was assessed as having lower scar severity than the untreated cheek. That description identifies what the study set out to measure.

The record does not report the primary endpoint result, its confidence interval, or the number of participants included in the assessment. It therefore does not show how frequently the endpoint occurred or how precisely that frequency was estimated. No conclusion about the size or direction of a comparative result can be drawn from the study title or endpoint definition.

The registry also does not report the secondary GAIS result or an analysis method. The listed safety counts are descriptive and lack information needed to interpret attribution or make a comparative causal assessment. A completed study status does not itself provide evidence about the outcomes.

In general, a treatment comparison is most interpretable when it includes clearly defined outcomes, analysis populations, missing-data procedures, and estimates with uncertainty. Those elements are not available for the primary endpoint in the registry entries. The record’s design labels are informative, but the discrepancy between the split-face group title and parallel-model field remains unexplained.

Accordingly, the record supports a description of the research question and some trial characteristics, but not a conclusion about whether the measured outcome favored either side, how large any difference was, or how reliable an estimate would be. Those questions require reported outcome results and a transparent account of the analysis.

14. Why This Trial Matters Statistically

This study raises several useful statistical questions. Its primary outcome is a directional comparison of the treated and untreated cheeks within participants. Such a comparison can use the participant as their own reference, but the analysis must account for the relationship between the two sides. This makes a clear description of allocation and statistical handling especially important.

The registry’s design fields do not fully align: the group title describes a split-face comparison, while the model is listed as parallel. This is not enough to determine how the study was implemented, but it highlights why design labels should be read alongside the detailed protocol and analysis plan. The registry record does not supply that clarification.

The endpoint is reported as a percentage with a 95% confidence interval. That format could communicate both the observed frequency and its uncertainty, but neither the numerical result nor the interval is reported in the available record details. Without those estimates, readers cannot distinguish a precise result from an uncertain one or judge the scale of the observed finding.

The record also illustrates the difference between a study status and a statistical result. It is listed as completed, yet the primary and secondary outcome results and analysis entries are not reported. Enrollment alone cannot fill that gap because the number assessed and the handling of missing data are not stated.

Finally, the safety figures require context about attribution in a split-face comparison. Descriptive counts are important, but without details of event classification and analysis they cannot be treated as evidence of a causal difference. Together, these features make transparent reporting of outcome definitions, denominators, analysis methods, and uncertainty central to evaluating this trial statistically.

15. 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 primary limitation for interpretation is that the registry record does not report the primary outcome estimate or its confidence interval. The endpoint is described, but its observed frequency and precision cannot be assessed. The analyzed denominator and the number of participants with a Month 3 assessment are also not reported.

The record lists 49 enrolled participants, but it does not give participant flow, withdrawals, or reasons for missing assessments. Missing-data handling and analysis populations are not reported in the registry record. These omissions prevent evaluation of whether the outcome analysis represents all randomized participants or a selected subset.

The design description is incomplete for reproducing the comparison. The group title refers to a split-face arrangement, while the model is recorded as parallel. The record does not explain the discrepancy, side allocation, randomization process, or how evaluator blinding was maintained. It also does not describe the statistical method for handling within-participant comparisons.

The primary endpoint description does not specify how equal severity between cheeks was classified or how scar severity was measured. The secondary GAIS outcome is listed without a reported result in the details available for this analysis. Multiplicity procedures are not reported.

The condition field says Healthy Volunteers even though the title concerns depressed facial acne scars; the registry does not clarify the label. The serious adverse event counts also lack detail on attribution and event-level classification. These limitations reflect gaps in the registry record and do not establish that the underlying study lacked such procedures or data.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Performance and Safety of Restylane Lidocaine for Treatment of Depressed Facial Acne Scars — NCT03127384.
• Registry record last updated 2022-08-26; status last verified 2019-09.
• Results first posted 2019-10-03.
• 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.

19. Record Summary

NCT03127384 is recorded as a completed Phase 4 randomized study sponsored by Galderma R&D. The registry lists enrollment of 49, a start date of 2017-04-20, and a primary completion date of 2018-02-15. The intervention was intradermal Restylane Lidocaine, compared with no-treatment control.

The primary outcome concerns the percentage of participants with lower scar severity in the treated cheek than in the untreated cheek at Month 3, assessed by a blinded evaluator. A secondary outcome concerns improvement on the Global Aesthetic Improvement Scale.

The registry record does not report the primary result, its confidence interval, or an analysis method. Analysis populations, missing-data handling, and multiplicity procedures are also not reported. The record’s split-face group title and parallel-model designation are not reconciled.