Changing in Skin Physiology After Microdroplet Placement of Stabilized Hyaluronic Acid in Aging Faces: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Changing in Skin Physiology After Microdroplet Placement of Stabilized Hyaluronic Acid in Aging Faces (NCT02312154), a non-randomized phase 4 study. The primary outcome is Hydration Level.

2. Clinical Question

The study also set out to assess safety and clinical appearance, and to examine changes in skin physiology over follow-up. The brief summary describes assessments of hydration, melanin content, erythema, and elasticity at 0, 1, 2, 4, 8, and 12 weeks after injection. Clinical improvement was assessed with the Global Aesthetic Improvement Scale at each visit. Those broader aims do not change the primary endpoint: hydration at 12 weeks. The registry record does not report enough numerical outcome information to establish the size or precision of the primary comparison.

3. Trial Design

The registry classifies this as a Phase 4, single-group study with nonrandomized allocation and single masking. It lists 25 participants as enrolled and the study status as completed. The brief summary describes a prospective, evaluator-blinded, balanced split-face study at a single center, with one cheek treated and the other left untreated. It says 24 participants completed follow-up.

There is an important design inconsistency in the registry record. The allocation field says nonrandomized, while the brief summary calls the study randomized and says the cheek side receiving treatment was chosen randomly. The arm description identifies the left side as treated and the right side as untreated. Because these statements do not agree, the record does not establish unambiguously whether treatment side was randomized. The appropriate interpretation is a split-face comparison whose allocation details are inconsistent, not a confirmed randomized comparison.

The paired structure is useful because measurements from two cheeks of the same participant share many characteristics. A within-person comparison can therefore account for some differences between participants. It does not, however, remove the need for sound allocation and analysis: side-specific differences, measurement error, and changes over time can still affect the comparison.

The summary states that a dermatologist unaware of the treatment side evaluated the skin measurements. It also says subjects and two independent investigators assessed clinical improvement. The exact role of each assessor in the registry’s single-masking designation is not reported in the registry record. Follow-up was scheduled at 0, 1, 2, 4, 8, and 12 weeks postinjection. The primary endpoint timeframe was 12 weeks.

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 Hydration Level, measured over 12 weeks.

The primary endpoint is hydration level at 12 weeks, measured in arbitrary units by a corneometer. The registry describes the measure as a continuous outcome, with the planned summary expressed as a mean and standard deviation. The instrument’s stated scale runs from 0 AU, described as as dry as possible, to 120 AU, described as most moist possible.

Hydration is a direct measurement of a skin property relevant to the study’s stated aim of assessing skin physiology after injection. Using an instrument gives a quantitative measurement that can be compared between the treated and untreated cheeks, rather than relying only on a subjective impression. In a split-face design, the key scientific contrast is the difference between sides within a participant at the specified follow-up time. The registry record does not report the actual mean hydration values, the within-person difference, or a confidence interval for that comparison.

A mean describes the central value of a set of measurements; a standard deviation describes their spread. Neither alone describes how precisely the treatment-side contrast has been estimated. For that, the result would need an uncertainty measure such as a confidence interval. The endpoint definition is reported, but its numerical result and uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a paired comparison mean?

In a split-face study, both sides of a participant are measured, with one side treated and the other untreated. The observations are paired because they come from the same person. A statistical comparison should respect that pairing: it focuses on the within-person contrast rather than treating each cheek as if it came from an unrelated participant. This matters because people differ in baseline skin characteristics, and those shared participant-level features can influence measurements on both sides.

Pairing can make a comparison more informative when the two sides are otherwise comparable and measurements are collected consistently. It does not automatically resolve differences between left and right sides, differences in treatment assignment, or changes in measurement conditions. In this study, the record conflicts over whether the treated side was randomly chosen, so the allocation process cannot be treated as settled.

How should a mean and standard deviation be read?

The primary outcome is a continuous measurement, and the registry indicates that it is summarized as a mean with a standard deviation. A mean gives a central summary of measured hydration. The standard deviation describes variability among measurements; it is not the uncertainty around the estimated treatment contrast. To understand the treatment-side comparison, readers would need the paired contrast and an uncertainty estimate for it.

A confidence interval is a general statistical way to express uncertainty around an estimate. It indicates which values remain reasonably compatible with the data under the method’s assumptions. A narrower interval indicates greater precision; a wider interval indicates more uncertainty. A confidence interval is not reported for the primary comparison in the registry record. Without one, the precision of the estimated effect cannot be evaluated.

What can a p-value tell readers?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be, assuming that hypothesis and the statistical model are correct. It does not measure the probability that the null hypothesis is true, the probability that a result occurred by chance, or the size or importance of an effect. A p-value also does not replace an effect estimate and its confidence interval. No p-value for the primary comparison is reported in the registry record.

The statistical analysis plan, including the exact test or model used for the primary comparison, is not reported in the registry record. It would therefore be inappropriate to claim that a particular paired test, adjustment, or model was used. General statistical explanations can clarify what such methods would address, but cannot establish which method was applied in this study.

Why do repeated measurements need care?

The brief summary describes assessments at 0, 1, 2, 4, 8, and 12 weeks. Measurements from the same participant across visits are correlated: they are not independent observations. Analyses of change over time generally need to account for that repeated-measures structure. A separate comparison at each visit would raise additional questions about multiplicity and interpretation. The registry record does not report the model or testing strategy used across visits.

Measurements may also be unavailable at some visits. Methods that use repeated observations can make assumptions about why data are missing, and different assumptions can lead to different estimates. The record reports 24 study completers but does not state the number of available hydration measurements at each time point or the method used to handle missing measurements.

Why can over-dispersion matter?

As a general concept, over-dispersion occurs when observed variability is greater than a statistical model expects. It is especially relevant to count outcomes, where a basic model may assume a particular relation between the mean and variance. If variation is larger than assumed, standard errors can be too small and intervals or tests can appear more precise than warranted. The primary endpoint in this study is a continuous hydration measure, not a count outcome. The registry record does not identify an over-dispersion assessment or a method that accounts for it, so it should not be assumed to have been part of the analysis.

What do planning sample sizes mean?

Sample-size calculations are planning tools that ask how many participants might be needed under specified assumptions to detect a chosen effect with a stated power and significance level. The registry describes a planning illustration using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. The numerical planning outputs are not reported in the registry record.

These illustrations are not observed power, and they do not show the probability that the completed study detected an effect. Their relevance depends on assumptions about the effect, variability, design, and analysis. Since the record does not report a numerical primary effect or the study’s own sample-size justification, the illustration should be understood only as a planning exercise, not as evidence about the precision or success of this trial.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Treated Side (Restylane Vital)", "Untreated Side")
n   <- c(24, 24)
m   <- c(53.19, 46.75)
sp  <- c(9.08, 9.24)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Treated Side (Restylane Vital)  24  53.190  9.080  49.356  57.024
CARM  Untreated Side  24  46.750  9.240  42.848  50.652

11. Multiplicity, Missing Data and Analysis Populations

The brief summary describes several skin physiology assessments: hydration, melanin content, erythema, and elasticity. It also describes clinical improvement ratings using the Global Aesthetic Improvement Scale. The registry record lists six outcome measures and six analyses, but does not give enough detail to determine exactly which comparisons were included in each analysis or how they were ordered.

When several outcomes, time points, or comparisons are examined, the chance of at least one apparently notable result can increase. General approaches to multiplicity include identifying a single primary comparison in advance, adjusting inference across a family of tests, or clearly labeling other analyses as exploratory. The statistical plan and any multiplicity adjustment are not reported in the registry record. Since numerical results are also absent, the impact of multiple testing cannot be assessed.

The study reports that 24 participants completed follow-up, but the number of observations available for each outcome and visit is not reported in the registry record. The record does not state whether analyses included all enrolled participants, only completers, or a different analysis population. It also does not describe imputation, exclusion criteria for analysis, or sensitivity analyses for missing data.

These details matter because an analysis of complete observations can differ from one that includes participants with partial follow-up, and missingness can affect estimates if it is related to outcome or treatment. Completion figures alone do not establish that the endpoint data were complete. The analysis populations, missing-data assumptions, and methods are not reported in the registry record.

12. 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 lists 24 participants at risk for serious adverse events and 0 participants affected by a serious adverse event in the Restylane Vital group. It lists 24 participants at risk for other adverse events and 24 affected. These are separate registry categories; the record does not supply further detail about the types, severity, timing, or attribution of the other adverse events. No serious adverse event terms are listed.

The brief summary states that no participants withdrew due to adverse effects. That statement is about withdrawal and should not be interpreted as meaning that no adverse events occurred: the registry’s other-adverse-event count is 24 affected. The serious adverse event count is also distinct from the number of other events. The death count is not reported in the registry record.

These figures describe what is recorded for this study; they do not establish that an event was or was not caused by treatment. Counts from a study of this size also provide limited information about uncommon harms. The registry record does not provide event-level descriptions or an attribution assessment, so those details cannot be inferred from the totals alone.

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

The study addresses a focused measurement question: whether hydration at 12 weeks differed between a cheek treated with stabilized hyaluronic acid and the untreated cheek of the same participant. The record specifies the instrument, outcome unit, and timeframe. It also documents a split-face approach and reports participant completion. These details help readers understand what was intended to be measured.

However, the numerical primary outcome is not reported in the registry record. There is no reported hydration mean for either side, estimate of the paired contrast, confidence interval, or p-value. Without those quantities, the direction and size of the observed comparison and its precision cannot be characterized. The record therefore does not permit a statistical conclusion about the primary endpoint.

The design could support a within-participant comparison, but the allocation information is inconsistent: the registry classifies allocation as nonrandomized, while the summary says treatment side was randomized. The arm description also assigns treatment to the left side. This inconsistency limits confidence about how side assignment was conducted and prevents treating random allocation as established.

The stated objective includes efficacy and safety, but an objective is not an outcome result. The serious adverse event count is recorded as 0 affected among 24 at risk, while 24 participants are recorded as affected by other adverse events. The record does not give details of those other events or establish causation. The brief summary says no participant withdrew because of adverse effects, which is a separate observation.

Accordingly, this record is informative about the study’s setup and the categories of outcomes collected, but not about the magnitude or precision of its primary finding. It cannot, on its own, establish whether the hydration contrast was clinically important, statistically distinguishable from no difference, or reproducible in another population.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its split-face structure creates a paired comparison. Each participant contributes a treated cheek and an untreated cheek, allowing the main contrast to be made within the same person. Such designs can reduce the influence of participant-level differences that would complicate comparisons between separate groups. The design also makes careful treatment-side allocation and analysis essential.

The registry record illustrates why design labels and narrative descriptions need to be read together. Allocation is listed as nonrandomized, but the brief summary describes random selection of the cheek side. The arm description specifies a treated left side and untreated right side. These details do not align, and the uncertainty affects how confidently readers can interpret the comparison as randomized.

The study also emphasizes the distinction between outcome definitions and outcome evidence. Hydration is clearly identified as the primary endpoint, with an instrument, unit, and follow-up timeframe. Yet the numerical endpoint result and its uncertainty are not reported in the registry record. A well-defined outcome does not by itself communicate what was observed or how precisely it was estimated.

Finally, the record makes visible the difference between participant completion, adverse-event counts, and analysis populations. Twenty-four participants completed the study; the summary says none withdrew due to adverse effects; and the registry lists different counts for serious and other adverse events. These registry entries address distinct questions and should not be collapsed into a single interpretation of safety or data completeness. The missing analysis details further limit evaluation of how the repeated measurements and multiple outcomes were handled.

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 most consequential limitation of the registry record for statistical interpretation is the absence of numerical results for the primary hydration endpoint. Means, a treated-versus-untreated estimate, confidence interval, and p-value are not reported in the registry record. The magnitude and precision of the primary comparison therefore cannot be evaluated.

Design information is internally inconsistent. The allocation field describes a nonrandomized study, while the summary calls it randomized and says that the treatment side was chosen randomly. The arm descriptions identify the left cheek as treated and the right cheek as untreated. The record does not resolve these statements, leaving uncertainty about the allocation process and the interpretation of side-to-side differences.

The brief summary reports 25 participants recruited and 24 completing the study, but does not report outcome availability at each visit or the analysis population. The approach to missing measurements, exclusions, and incomplete follow-up is not reported in the registry record. This is relevant because the schedule includes multiple measurements over time.

The statistical analysis plan, including the analysis for the paired primary comparison, handling of repeated measurements, and any multiplicity strategy, is not reported in the registry record. The record identifies several outcomes and analyses but does not give sufficient detail about their hierarchy or relationship. The sample-size justification used to design the study is also not reported in the registry record.

Safety interpretation is limited by the absence of descriptions for the other adverse events and by the lack of an event-attribution assessment. The serious-event count and the other-event count are reported separately, but the record does not describe event timing or severity beyond those categories. These limitations constrain interpretation of the posted information and should not be filled by assumptions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Changing in Skin Physiology After Microdroplet Placement of Stabilized Hyaluronic Acid in Aging Faces — NCT02312154.
• Registry record last updated 2015-04-03; status last verified 2015-03.
• Results first posted 2015-02-24.
• 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

The registry describes a completed Phase 4 study of Restylane Vital for aging facial skin. It lists 25 participants enrolled and a single-group, nonrandomized allocation, while the brief summary describes a split-face study and says the treated cheek side was randomly chosen. The treatment was a single injection to one lower cheek; the other cheek was untreated.

Hydration level measured by corneometer at 12 weeks is the primary outcome. Follow-up assessments were described at 0, 1, 2, 4, 8, and 12 weeks. The brief summary reports that 24 participants completed the study and that no participants withdrew due to adverse effects.

The registry lists 0 serious adverse event participants affected among 24 at risk, and 24 participants affected by other adverse events among 24 at risk. Numerical primary hydration results, the statistical analysis plan, analysis populations, and missing-data methods are not reported in the registry record. The allocation descriptions also remain inconsistent.