A Safety and Effectiveness Study of JUVÉDERM VOLBELLA® XC Injectable Gel for Lip and Perioral Enhancement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Effectiveness Study of JUVÉDERM VOLBELLA® XC Injectable Gel for Lip and Perioral Enhancement (NCT01998581), a randomized na study. The primary outcome is Change From Baseline in Evaluating Investigator's Assessment of Lip Fullness on a 5-Point Scale.

2. Clinical Question

3. Trial Design

The registry describes a multicenter, double-blind, randomized, controlled, parallel study of JUVÉDERM VOLBELLA® XC and Restylane-L® for lip and perioral enhancement. The study enrolled 225 participants and is marked completed. Its recorded start date is 2013-11-01, and its primary completion date is 2014-08-04. The phase is listed as NA. Allergan is identified as the sponsor.

Random allocation means assignment to the study arms was intended to occur by chance. In general, randomization helps reduce systematic differences between groups at the start of a trial, although it does not guarantee that every characteristic will be balanced. A double-blind designation means that the record characterizes the study as masked at two levels; the registry record does not specify which people were masked or how masking was maintained. It also does not report whether masking was assessed.

The primary endpoint population was not simply all enrolled participants. It was defined as randomized subjects with a baseline Lip Fullness Scale 2 score of minimal, mild, or moderate who received at least 1 treatment. The registry record does not report the number of participants included in that population or the numbers assigned to each initial treatment arm. It lists a JUVÉDERM VOLBELLA® XC repeat-treatment group in the safety information, but does not provide the timing or eligibility rules for repeat treatment.

The listed secondary outcomes concern change from baseline in subject satisfaction with lips on the Lip Module of the FACE-Q Questionnaire, and the percentage of subjects in the JUVÉDERM VOLBELLA® XC arm with at least a 1 point improvement from baseline on the Perioral Lines Severity Scale. The record lists 3 outcome measures overall, but does not report their results or the analysis procedures used for them.

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:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat: subjects who were randomized with a Lip Fullness Scale 2 baseline score of minimal, mild, or moderate and who received at least 1 treatment

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: Safety Population: Subject who received at least 1 treatment

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Evaluating Investigator's Assessment of Lip Fullness on a 5-Point Scale, measured over Baseline, Month 3.

The primary endpoint is change from baseline in the evaluating investigator’s assessment of lip fullness on the Lip Fullness Scale 2, at Baseline and Month 3. The scale is described as having 5 points, from 0, minimal or nearly flat contour with minimal red lip show, to 4, very marked red lip show with lower- and upper-lip pout. The registry describes the lower end as worse and the upper end as best. A positive change from baseline indicates improvement; a negative change indicates worsening.

The endpoint is intended to capture change in lip fullness as rated by an evaluating investigator, rather than a participant’s satisfaction or assessment of perioral lines. An investigator rating can provide a structured outcome for comparing changes between randomized groups. General statistical context: measuring change from baseline focuses attention on how scores move over the follow-up period, while group comparisons are needed to distinguish change within a group from differences associated with treatment assignment.

The registry specifies a mean and standard deviation as the summary measures for this continuous outcome. It does not report the mean changes, their variability, a treatment-group contrast, a confidence interval, or a significance test. Consequently, the direction and size of any observed difference in the primary endpoint cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is recorded as a mean change in a continuous measure, with standard deviation used to describe dispersion. General statistical context: a mean summarizes the average value in a group, while a standard deviation describes how spread out individual values are around that average. The mean can make a group’s overall change easy to describe, but it does not show the range of individual experiences or the distribution’s shape. The standard deviation is not the same as the uncertainty in the mean or in a difference between groups.

What does change from baseline represent?

For each participant, change from baseline is the follow-up score compared with that participant’s starting score. The registry specifies Baseline and Month 3 and says that a positive change indicates improvement while a negative change indicates worsening. General statistical context: an analysis of change can account for where participants started, but interpretation still depends on how the trial handles missing follow-up measurements, the analysis population, and the comparison between randomized arms. The registry record does not describe those analysis details beyond the primary population definition.

The measure is a rating on the Lip Fullness Scale 2, with scores running from 0 to 4. Although the registry identifies the summary parameter as a mean, the scale is based on ordered categories with descriptive anchors. General statistical context: reporting a mean for a rating scale can provide a compact group summary, but it treats the distances between score values as meaningful for purposes of averaging. The record does not describe any alternative summaries or sensitivity analyses for this outcome.

Why compare randomized groups?

A change within one group alone does not isolate the effect of assignment to that group. General statistical context: a randomized controlled comparison focuses on the difference in outcomes between assigned groups, because changes can also reflect factors shared by participants over time, measurement variation, or other influences. Randomization is intended to make the groups comparable on average at the start; it does not remove the need to report the comparison, its uncertainty, and the analysis population.

The registry design is parallel, meaning the record describes separate treatment groups rather than a crossover comparison. It also identifies the study as double-blind. In general, masking can reduce the chance that knowledge of assignment influences ratings or other study procedures. The record does not describe who was masked, how masking was implemented, or whether the evaluating investigator was among those masked. Those details are not reported in the registry record.

How should precision be judged?

General statistical context: a confidence interval around a treatment-group difference communicates uncertainty about the estimated contrast. A narrow interval indicates greater precision than a wide interval, though precision is not the same as clinical importance. A p-value addresses compatibility of the data with a specified null hypothesis under an analysis model; it does not report the probability that a treatment is effective or ineffective. The registry record does not report a confidence interval, a p-value, or another measure of uncertainty for the primary outcome.

The study summary identifies a 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; the illustration is described as targeting a stated fraction of the observed effect. These are assumptions for a planning calculation, not a description of the trial’s original design justification. The registry record does not report the original sample-size justification. Because primary-outcome results are not reported, the observed effect underlying any such illustration is not available in this record. Planning sample sizes are not observed power and do not show how likely the completed trial was to detect a particular effect.

Why might variation matter?

General statistical context: greater variability among individual outcomes can make a group mean less precise, all else being equal. If data are more dispersed than an analysis model assumes, standard errors and tests based on that model may not describe uncertainty well. In count outcomes, over-dispersion means variability exceeds what a simple count model expects; that concept is not the stated model for this continuous primary endpoint. The record does not report an over-dispersion assessment or an alternative model, and such methods should not be assumed to have been used.

For a continuous endpoint, the choice of analysis can also depend on distributional features, baseline values, and missing observations. General statistical context: prespecified adjustment for baseline or other variables may improve precision when appropriately specified, but any adjusted estimate should be interpreted with its model assumptions. The registry record does not report whether the primary analysis was adjusted, which model was used, or whether assumptions were checked. It also does not report whether results were analyzed according to assignment or according to treatment received.

What is not available for checking?

The record gives the endpoint definition and identifies a modified intent-to-treat population, but does not report participant flow into that population, outcome counts at Month 3, the statistical model, handling of missing observations, or an effect estimate. It lists 0 analyses. This limits independent assessment of the calculation and of the sensitivity of the result to assumptions. These omissions do not show that the analysis was not performed; they mean that its details and results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures: the primary change in investigator-rated lip fullness, improvement in perioral lines in the JUVÉDERM VOLBELLA® XC arm, and change in subject satisfaction with lips on the FACE-Q Lip Module. It lists 0 analyses. The record does not report a statistical testing hierarchy, a multiplicity adjustment, or whether any secondary outcome was considered confirmatory. General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the multiple testing. The record does not describe whether or how that issue was addressed.

The primary population is defined as randomized subjects with a baseline Lip Fullness Scale 2 score of minimal, mild, or moderate who received at least 1 treatment. This is the population description available for the primary endpoint. The registry record does not report the number included in that analysis, the number excluded after randomization, or how many had a Month 3 measurement. It does not report a separate analysis population for the secondary outcomes.

Missing-data methods are not reported in the registry record. In general, missing outcomes can affect estimates if the participants with observed measurements differ from those without them. Statistical approaches make assumptions about the missingness process, and sensitivity analyses can examine whether conclusions depend on those assumptions. The record does not report the amount or pattern of missing primary-outcome data, the method used to handle missingness, or any sensitivity analysis.

The record also does not report interim analyses, stopping rules, or a prespecified statistical analysis plan. Their absence from the registry record should not be treated as evidence that no such procedures existed.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: non-small cell lung cancer stage iii (1.8%), colitis (0.6%), procedural pain (0.6%), cervical spinal stenosis (0.6%), goitre (0.6%).

The registry lists serious adverse event counts for the JUVÉDERM VOLBELLA® XC initial-treatment group, the Restylane-L® group, and the JUVÉDERM VOLBELLA® XC repeat-treatment group. The respective numbers at risk are 168, 56, and 30. The serious-event affected counts are 5, 1, and 0. These are descriptive counts; the record does not provide a comparative safety analysis or uncertainty estimates for them.

The listed counts for other adverse events are 85 of 168 for the JUVÉDERM VOLBELLA® XC initial-treatment group, 28 of 56 for the Restylane-L® group, and 12 of 30 for the repeat-treatment group. The registry’s labels distinguish serious adverse events from other adverse events, so those categories should not be combined. The record does not describe event collection methods, follow-up duration for these safety counts, or whether events were considered related to treatment.

The serious-event terms listed include Non-Small Cell Lung Cancer Stage III at 1.8%, and Colitis, Procedural Pain, Cervical Spinal Stenosis, Goitre, and Malignant Sweat Gland Neoplasm, each at 0.6%. The registry does not specify the group attribution for these terms in the listed summary. Death counts are not reported in the registry record.

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

The record establishes that a completed, randomized, double-blind, controlled study was conducted to compare JUVÉDERM VOLBELLA® XC with Restylane-L® for lip and perioral enhancement. It identifies a primary outcome focused on investigator-rated change in lip fullness from baseline to Month 3, along with two secondary outcomes. It also defines the population intended for the primary endpoint and reports selected safety counts.

That information describes the question and some features of the study, but it does not establish the study’s primary result. The record does not report the mean change in either initial treatment group, the difference between groups, a confidence interval, or a statistical test. It therefore does not show the direction, size, or precision of a treatment-group difference in investigator-rated lip fullness. The same limitation applies to the listed secondary outcomes: their results are not reported in the registry record.

General statistical context: a statistically significant result, if reported, would not by itself show that an effect is large or important. Conversely, a result that is not statistically significant would not by itself show that the groups are equivalent. Effect estimates and uncertainty intervals are needed to assess what the data are compatible with. No such primary-outcome estimates are reported in the registry record.

The safety counts provide descriptive information for the named groups, but do not establish comparative risk. The groups have different numbers at risk, and the record does not report an adjusted comparison, follow-up details, or attribution of events to treatment. The listed serious-event terms also lack group attribution in the provided safety summary. These figures should not be interpreted as a complete safety assessment.

In short, the registry record documents the study’s intended comparison, measurement, and selected safety information. It does not report enough outcome data to determine how the treatments compared on the primary endpoint or how precise any difference was. No conclusion about treatment benefit or lack of benefit follows from the endpoint description or the enrollment count alone.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it pairs random assignment and masking with an investigator-rated outcome intended to measure change over time. The registry specifies the outcome scale, the direction of improvement, the primary follow-up at Month 3, and a defined analysis population. Those details matter when interpreting a clinical trial: a result is only meaningful when readers can tell what was measured, in whom, and at what time.

The record also illustrates why design descriptions and result reporting are distinct. Randomization and double-blind masking describe intended safeguards against bias, while the primary endpoint definition describes the target measurement. Neither gives the estimated contrast or its uncertainty. For statistical interpretation, reporting group-level results and a between-group estimate is essential; those primary results are not reported in the registry record.

The primary population definition is another important feature. It restricts the endpoint analysis to randomized subjects with specified baseline lip-fullness categories who received at least 1 treatment. This means the enrolled total of 225 should not automatically be treated as the number analyzed for the primary endpoint. The record does not report the analysis count or participant flow.

Finally, the listed safety counts show why different types of evidence should be kept separate. Serious and other adverse events are reported descriptively, while the primary outcome concerns a change in an investigator rating. Without outcome estimates, uncertainty measures, and fuller analysis details, the record supports understanding the study’s structure but not a statistical judgment about the comparative primary outcome.

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.

The central trial-specific limitation is that the registry record does not report results for the primary endpoint. It defines the investigator-rated lip-fullness measure and its Month 3 timeframe, but gives no group means, between-group estimate, confidence interval, or p-value. The secondary outcome results are also not reported. This prevents assessment of effect direction, size, and precision.

The record states an enrollment of 225 but does not report the number randomized to each initial treatment group, the number included in the primary population, or the number with outcome measurements at Month 3. Although the primary population is defined, participant flow and exclusions are not reported. Missing-data methods and outcome completeness are also not reported in the registry record.

The registry does not report the statistical model, baseline adjustment, sensitivity analyses, multiplicity procedures, or the original sample-size justification. It lists 0 analyses and does not provide an interim-analysis or stopping-rule description. The planning assumptions described in the record are not a substitute for the original design justification or for the missing outcome estimates.

The safety summary gives counts for initial treatment and repeat treatment groups, but the record does not explain the repeat-treatment schedule or provide a comparative safety analysis. It does not report follow-up details for these counts, treatment attribution, or group attribution for the listed serious-event terms. Death counts are not reported in the registry record. These reporting gaps limit interpretation of the safety information as well as the efficacy endpoint.

These are limitations of the information reported in the registry record. They do not establish that the study lacked analyses or procedures that are not described there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Safety and Effectiveness Study of JUVÉDERM VOLBELLA® XC Injectable Gel for Lip and Perioral Enhancement — NCT01998581.
• Registry record last updated 2019-04-26; status last verified 2019-04.
• Results first posted 2016-12-05.
• 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

The registry record describes NCT01998581, a completed multicenter, double-blind, randomized, controlled, parallel study sponsored by Allergan. It enrolled 225 participants, with a recorded start date of 2013-11-01 and primary completion date of 2014-08-04. The study compared JUVÉDERM VOLBELLA® XC with Restylane-L® for lip and perioral enhancement.

The primary endpoint was change from baseline to Month 3 in evaluating-investigator assessment of lip fullness on the Lip Fullness Scale 2. The primary population was defined as randomized subjects with specified baseline scores who received at least 1 treatment. Two secondary outcomes were listed, for 3 outcome measures overall. The registry lists 0 analyses and does not report primary or secondary outcome results.

Safety information includes serious and other adverse-event counts for initial JUVÉDERM VOLBELLA® XC treatment, Restylane-L®, and repeat JUVÉDERM VOLBELLA® XC treatment. The record does not report a comparative safety analysis or death counts.