Princess® VOLUME Lidocaine for the Correction of Nasolabial Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Princess® VOLUME Lidocaine for the Correction of Nasolabial Folds (NCT03050710), a na na study. The primary outcome is NLF-SRS Grade of Nasolabial Folds Change.

2. Clinical Question

The study concerns people with moderate to severe nasolabial folds who were treated with Princess® VOLUME Lidocaine. Its registry description frames the treatment as an injection into the deep dermis or subcutis, with the amount selected by the investigator according to the area requiring correction.

The NLF-SRS is described as a validated 5-point scale, ranging from Grade 0, none or minimal, to Grade 4, extreme. A lower grade represents improvement from an aesthetic perspective. The central statistical question is therefore about the size and precision of the average within-group change, not whether treatment outperformed a control. Without a reported estimate and uncertainty measure, the magnitude of change and the precision with which it was estimated cannot be assessed from the registry record.

3. Trial Design

This was a prospective, open-label, multicenter, post-market study of Princess® VOLUME Lidocaine for correction of nasolabial folds. The registry lists the study as completed, with enrollment of 62. The listed study start was 2016-12-27 and primary completion was 2017-07-18. Croma-Pharma GmbH is identified as the sponsor. The phase and allocation are listed as NA, and masking is listed as NONE.

The design is single-group: participants received the intervention, and the registry does not identify a separate control arm. The planned follow-up assessments were at 2, 4, 24 and 36 weeks after treatment. A touch-up at Week 2 could be performed if the investigator considered it appropriate. These are descriptions of the study plan; the registry record does not report how many participants completed each assessment or how often a touch-up was used.

The intervention description says that injections were administered into the deep dermis or subcutis. The investigator selected the volume according to the size of the area requiring correction, subject to a maximum total of 10 mL per treatment. The registry's brief summary describes eligible subjects with moderate to severe folds, while the primary outcome population is called the ITT population and is defined by reference to a baseline analysis population description.

Because there is no concurrent comparator, change from baseline can describe the course of scores among treated participants but cannot isolate the treatment's effect from other explanations for change. Open-label assessment also means that participants and investigators were not masked according to the registry record. The record does not report details of assessor training, measurement procedures beyond investigator evaluation, or measures used to reduce assessment bias. Those omissions matter when interpreting a subjective or clinician-rated outcome.

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

Analysis population for the primary outcome, as defined in the registry: ITT - Intent to treat Population - as defined in Baseline Analysis Population Description

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: 62 screened subjects were treated at least once with the investigational medical device and were included in the SAF. 62 subjects had at least one post-treatment assessment and at least one NLF severity assessment based on the NLF-SRS and were included in the ITT population. One subject terminated the investigation early after Week 4 due to a clinical investigation plan (CIP) deviation.

6. Primary Endpoint

The registry lists the primary outcome as NLF-SRS Grade of Nasolabial Folds Change, measured over 24 weeks.

The primary endpoint is the average change from baseline in the investigator-assessed NLF-SRS grade of nasolabial folds at Week 24. It is a continuous outcome summarized by a mean and standard deviation, according to the registry record. The endpoint is defined for the ITT population, which the record says is defined in the Baseline Analysis Population Description.

The NLF-SRS is described as a validated 5-point scale running from Grade 0, none or minimal, to Grade 4, extreme. A reduction in grade represents improvement from an aesthetic perspective. Measuring change from baseline focuses on how scores at follow-up compare with each participant's starting score; averaging those changes gives a group-level description of the direction and magnitude of change. The scale's bounded range is relevant: scores cannot extend beyond its stated grades, and the meaning of an average change depends on the starting scores and the distribution of individual changes.

This endpoint is used to assess fold severity at a prespecified follow-up, but the registry record does not report the Week 24 mean change, its standard deviation, a confidence interval, or an inferential test. The endpoint definition alone does not establish how much change occurred, how variable individual changes were, or how precisely the average was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a mean change in a continuous measure, with standard deviation as its dispersion summary. These are descriptive statistics. The mean expresses the average of the observed changes, while the standard deviation describes how spread out those changes are around the mean. The standard deviation is not the same as the uncertainty in the estimated mean: uncertainty in a mean is generally summarized by a standard error or confidence interval. Neither the primary estimate nor an interval is reported in the registry record.

What does the mean change represent?

For each participant with the relevant measurements, change from baseline represents the difference between the follow-up score and the baseline score. The group mean then summarizes those changes. Since lower NLF-SRS grades indicate less severe folds, a negative change under the usual follow-up-minus-baseline convention would correspond to a lower score; however, the registry record does not state the calculation convention or report the estimate. The direction can therefore be understood from the stated scale interpretation, but the actual result cannot be reconstructed.

Means can be informative, but a mean alone may obscure variation in responses. A group can have an average change even when some participants' scores change more than others, or move in different directions. The standard deviation would help characterize spread, but no value is reported. The underlying grade distribution, individual-level data, and proportions reaching particular changes are also not reported in the registry record.

Why does the scale matter?

In general, ordinal scales have ordered categories, but the distance between adjacent categories is not necessarily equal. A mean treats the numerical spacing as meaningful for averaging. The NLF-SRS is described as a validated 5-point scale, and the registry specifies a mean endpoint, so the mean is the planned summary. Nonetheless, interpretation benefits from knowing the distribution across grades and changes, which the registry record does not report. A bounded scale also limits possible values and can make the distribution depend on participants' starting grades.

In general, over-dispersion means that observed variability is greater than a statistical model assumes. If a model assumes less variation than the data contain, standard errors can be too small and uncertainty can be understated. This issue is most relevant when a model's distributional assumptions are not a good fit. The registry record does not report a model for the primary endpoint, so it is not possible to assess whether over-dispersion was considered or whether a particular model was used.

What would an uncertainty interval add?

In general, a confidence interval communicates the range of values reasonably compatible with a data estimate under specified assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval width nor a p-value substitutes for judging the size and relevance of the effect. The registry record does not report a confidence interval for the primary endpoint, and it does not report a statistical test or p-value. No inferential conclusion can be drawn from the endpoint definition alone.

The registry includes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its stated effect to detect is a fraction of the observed effect. For time-to-event planning, the stated output is total events; for other outcomes, it is participants per arm. These are planning assumptions, not evidence about the trial's actual analysis, and sample-size illustrations are not observed power. The registry record does not report a trial-specific design justification or an observed primary-effect estimate that would allow the planning assumptions to be independently evaluated. Since the study itself is single-group, the equal-allocation two-arm assumption is a planning convention rather than a description of this trial's design.

The record lists 0 analyses. It does not report a statistical analysis plan, details of an inferential model, adjustment for baseline values, handling of repeated measurements, or sensitivity analyses. Such choices can affect uncertainty estimates and interpretation. Without them and without the numerical outcome results, the statistical analysis cannot be reproduced or assessed in detail from the registry record.

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("Princess® VOLUME Lidocaine")
n   <- c(61)
m   <- c(-1.5)
sp  <- c(0.58)
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  Princess® VOLUME Lidocaine  61  -1.500  0.580  -1.649  -1.351

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary Week 24 grade-change outcome and secondary measures addressing grade change or reduction at other timepoints, aesthetic improvement, satisfaction with aesthetic outcome, pain intensity, and imaging-independent reviewer assessment. It lists 0 analyses. Numerical results for the secondary outcomes, their analysis methods, and any hierarchy among them are not reported in the registry record.

When a study evaluates multiple outcomes or timepoints, in general, the chance of at least one apparently unusual result can increase if many statistical tests are conducted. A prespecified hierarchy, adjustment procedure, or distinction between primary and exploratory analyses can help readers understand how to interpret multiple findings. The registry record does not report whether multiplicity was addressed, so it is not possible to determine whether any secondary findings were intended to support confirmatory conclusions.

The primary outcome population is described as the ITT population and refers to a baseline analysis population description. Further details of that population definition and the analysis set are not reported in the registry record. The record also does not report how missing Week 24 measurements were handled, whether participants with incomplete follow-up were included in particular analyses, or whether sensitivity analyses assessed the impact of missing data. General statistical practice distinguishes the intended analysis population from the participants contributing measurements at a given follow-up; without the relevant accounting, the extent and consequences of missing data cannot be assessed.

Although the planned assessments include 2, 4, 24 and 36 weeks, the registry record does not report completion counts at those timepoints. It also does not report a method for handling repeated measurements or the role of the optional Week 2 touch-up in the analysis. These omissions leave uncertainty about the data contributing to each outcome and about whether the analysis followed a prespecified plan.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry's adverse-event summary lists 62 participants at risk in the Princess® VOLUME Lidocaine group. It records 0 participants affected by a serious adverse event, 12 affected by other adverse events, and 0 deaths. These are the posted counts; they should be read as counts in the registry summary, not as a complete account of every possible event or its circumstances.

The record does not list any top serious adverse-event terms. It does not report event descriptions for the 12 participants with other adverse events, event severity, timing, duration, relationship to treatment, or whether events led to discontinuation. The registry record also does not provide further detail about the rules used to classify events or the period over which participants were monitored for this summary.

A count of 0 serious adverse events in the posted summary means that none were recorded in that category in this summary. It does not establish that the intervention has no risk, nor does it rule out uncommon events or events not captured in the record. Likewise, the other-adverse-event count should not be interpreted as a rate without details of event definitions and follow-up. The safety figures are descriptive and do not compare the intervention with a control group, because this was a single-group study.

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

The registry record describes a study designed to assess change in nasolabial fold grade after treatment with Princess® VOLUME Lidocaine. Its primary question is about average change from baseline at Week 24, measured by investigator assessment using the NLF-SRS. The record explains the scale and its direction: a lower grade indicates improvement from an aesthetic perspective.

What the record does not report is the numerical Week 24 average change, its standard deviation, or a confidence interval. It therefore does not establish the size of the observed change or how precisely that change was estimated. Without the baseline grade distribution or individual change data, the relation between a group average and the range of participants' outcomes is also unknown. Secondary outcome descriptions do not substitute for numerical results, which are not reported in the registry record.

The study's single-group, open-label design also limits causal interpretation. A change between baseline and follow-up would be a within-group observation, not a direct estimate of the difference between treatment and no treatment or another intervention. No comparator group is identified, and the registry record does not describe a blinded assessment. As a result, the record cannot separate treatment-associated change from other possible influences on scores or ratings.

The posted safety summary records 0 participants with serious adverse events, 12 with other adverse events, and 0 deaths among 62 at risk. These counts are descriptive; event details and comparative safety data are not reported in the registry record. The counts do not establish that no safety concerns exist.

Accordingly, the record supports a description of the study question, endpoint, design, and listed safety counts. It does not provide enough numerical outcome information to characterize the primary result, its precision, or its clinical importance. The absence of a reported result should not be read as evidence of either benefit or no benefit.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a within-group change and a comparative treatment effect. Its prospective, single-group structure can describe scores over follow-up among participants who received Princess® VOLUME Lidocaine. Without a concurrent comparator, however, a change from baseline cannot by itself show how scores would have changed in the absence of treatment or under another intervention. That distinction is central to interpreting uncontrolled clinical studies.

The endpoint also illustrates how the choice of summary shapes interpretation. The registry specifies a mean change on a validated 5-point grade scale. A mean gives a compact group-level summary, while the standard deviation would describe the spread of observed changes. Neither measure is reported numerically in the registry record. The absence of these results prevents readers from assessing both magnitude and variability, and the absence of an uncertainty interval prevents assessment of precision.

Assessment is investigator-rated and the study is open-label. In general, ratings can be influenced by expectations, so information about masking, measurement procedures, and the distribution of scores is relevant to evaluating potential assessment bias. The registry record lists masking as NONE and does not provide further information on procedures to address this concern.

The record names several secondary outcome domains and multiple assessment timepoints. When multiple outcomes are studied, clear analysis plans and reporting of multiplicity handling help distinguish primary evidence from exploratory patterns. Those details are not reported in the registry record, which lists 0 analyses. This makes complete interpretation difficult even though the study question and planned endpoint are described.

The study is also useful as an example of why a completed status and a defined endpoint are not equivalent to a reported statistical result. The registry identifies the design and outcome but does not report the primary estimate or its uncertainty. Readers therefore need to distinguish the information available about what was planned and measured from the information needed to evaluate what was observed.

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 for statistical interpretation is that the registry record does not report the primary outcome estimate at Week 24. It also does not report its standard deviation, confidence interval, or test result. Consequently, neither the size of the average change nor the precision of that estimate can be assessed. The registry record does not report baseline grade distribution or individual changes, which would help contextualize a mean on a bounded scale.

The study is single-group, open-label, and has no listed comparator. Any within-group change cannot separate the course of scores after treatment from other influences, and the registry record does not describe blinded outcome assessment. The endpoint is investigator-assessed; further detail on assessment procedures or steps to limit rating bias is not reported in the registry record.

Although follow-up assessments are described at 2, 4, 24 and 36 weeks, the record does not report completion counts at each timepoint or how missing measurements were handled. It does not report analysis methods for repeated measurements, sensitivity analyses, or the detailed definition of the ITT population beyond referring to a baseline analysis population description. Whether and how the optional Week 2 touch-up affected later outcomes is also not reported.

The registry identifies 9 outcome measures but lists 0 analyses. Statistical methods for the primary and secondary outcomes, treatment of multiple comparisons, and distinctions between confirmatory and exploratory analyses are not reported. The adverse-event summary has limited detail about event types, timing, severity, attribution, and observation period. Together, these gaps restrict assessment of outcome reliability, missing-data effects, multiplicity, and safety context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Princess® VOLUME Lidocaine for the Correction of Nasolabial Folds — NCT03050710.
• Registry record last updated 2025-06-04; status last verified 2018-08.
• Results first posted 2025-06-04.
• 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, prospective, open-label, multicenter, post-market, single-group study of Princess® VOLUME Lidocaine for moderate to severe nasolabial folds. Enrollment is listed as 62. Assessments were planned at 2, 4, 24 and 36 weeks, with a Week 2 touch-up possible at investigator discretion.

The primary endpoint was average change from baseline in investigator-assessed NLF-SRS grade at Week 24 in the ITT population. The scale ranges from Grade 0, none or minimal, to Grade 4, extreme, and a reduction represents improvement from an aesthetic perspective. The registry record does not report the numerical primary result or its uncertainty.

The adverse-event summary records 0 serious adverse events, 12 participants with other adverse events, and 0 deaths among 62 at risk. Further event details and comparative safety data are not reported in the registry record. The absence of a comparator and of numerical outcome results limits conclusions about treatment effects and their precision.