Sequential Treatment With BELKYRA® Then Juvéderm® VOLUMA™ With Lidocaine for Overall Improvement in Jawline Contour: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sequential Treatment With BELKYRA® Then Juvéderm® VOLUMA™ With Lidocaine for Overall Improvement in Jawline Contour (NCT03425253), a na phase 4 study. The primary outcome is Percentage of Participants Who Showed ≥ 1-point Jawline Improvement From Baseline on the Allergan Loss of Jawline Definition Scale (ALJDS), as Assessed by the Investigator.

2. Clinical Question

3. Trial Design

This was a Phase 4, prospective, open-label, single-group study sponsored by Allergan. The registry record lists 58 participants as the enrollment and identifies the study status as completed. The recorded study dates are 2018-02-02 for the start and 2019-12-05 for primary completion.

The treatment sequence combined BELKYRA® for submental fat with Juvéderm® VOLUMA™ with Lidocaine to restore volume along the mandibular border. BELKYRA® was injected into subcutaneous preplatysma fat tissue in the submental area. The record describes at least 1 initial treatment and up to 5 optional additional treatments, with a maximum of 6 treatments 8 weeks apart. It also describes a decision point at which the investigator and participant agreed that no further intervention was required to achieve the desired result. Further procedural details for VOLUMA™ are not reported in the registry record.

Open-label means that masking was not used, consistent with the record’s masking entry of none. A single-group design has no concurrent treatment-control group in the listed study structure. The allocation entry is NA, so the record does not describe allocation between groups. The study can describe outcomes among participants receiving the sequence, but it does not provide a randomized between-group estimate of the treatment sequence versus another approach.

The primary assessment ran from Baseline (Day 0) to Week 58. The primary analysis population was restricted to participants who received both treatments and had a post-treatment efficacy assessment at the Exit Visit. Whether all enrolled participants met those criteria, and how many were included in that analysis, are not reported in the registry record. The record lists secondary assessments involving FACE-Q™ measures, clinician- and patient-reported submental fat ratings, skin laxity, and independent reviewer assessment of jawline definition.

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: Evaluable Set (ES) included participants who received both study treatments (i.e., both BELKYRA® and VOLUMA™) and had a post-treatment efficacy assessment at the Exit Visit.

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: FAS included all participants who received BELKYRA®.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Showed ≥ 1-point Jawline Improvement From Baseline on the Allergan Loss of Jawline Definition Scale (ALJDS), as Assessed by the Investigator, measured over Baseline (Day 0) to Week 58.

The primary endpoint is the percentage of participants who showed at least a 1-point improvement from baseline on the investigator-assessed Allergan Loss of Jawline Definition Scale (ALJDS), measured from Baseline (Day 0) to Week 58. The ALJDS describes loss of jawline definition on a 5-point scale: 0=none, 1=mild, 2=moderate, 3=severe, and 4=extreme. The registry record specifies results for both sides of the face, the right side, and the left side.

Turning a scale change into a responder percentage gives a direct description of how many participants crossed the stated improvement threshold. That can be easier to interpret than a mean score change alone, while also discarding information about the size of changes beyond the threshold. A participant with a larger improvement still contributes as a responder under this definition; the percentage does not convey the magnitude of that participant’s change.

As a general statistical point, the result depends on the baseline score distribution and on how scores are assessed at follow-up. The registry record describes the scale and threshold but does not report the underlying participant-level score distribution, the primary percentage, or its 95% confidence interval. The primary analysis population was the Evaluable Set, defined as participants who received both study treatments and had a post-treatment efficacy assessment at the Exit Visit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A responder endpoint converts a scale into a binary outcome: each participant either meets the specified improvement threshold or does not. In this study, the threshold is at least a 1-point improvement on the ALJDS from baseline. The responder percentage is the share of the analysis population that meets that definition. The primary population is the Evaluable Set, not automatically the full enrollment.

What does a confidence interval convey?

In general, a confidence interval describes uncertainty around an estimated quantity under the statistical method used to construct it. For a responder percentage, the interval gives a range of values compatible with the observed data and the method’s assumptions. A narrower interval generally indicates greater precision; a wider interval indicates more uncertainty. It does not show the range of individual participant outcomes, and it does not correct for limitations such as selection into the analysis population or the absence of a comparator.

The registry record identifies a 95% confidence interval for the primary endpoint, but its limits and the corresponding percentage are not reported in the registry record. Without the estimate and interval, neither the observed responder proportion nor its statistical precision can be assessed. The primary record also identifies results for both sides of the face and each side separately. Those are related assessments, but the numerical results for them are not reported in the registry record.

Why does the scale and threshold matter?

The ALJDS is an ordered, 5-point scale from 0=none to 4=extreme loss of jawline definition. A one-point movement is a change by one scale category, but the categories are ordinal: the scale indicates order and does not establish that every step represents an equal change in the underlying feature. The responder definition focuses on crossing the stated threshold. It can make the outcome readily interpretable as a proportion, but two responders may have different-sized improvements, and those differences are not reflected in the binary outcome.

In general, dichotomizing a scale can simplify communication while losing detail. A mean score change, a distribution of score changes, and a responder percentage answer related but distinct questions. The registry record lists secondary changes on the ALJDS and other outcomes, but their numerical results are not reported in the registry record. No conclusion about agreement among those measures can be drawn from their names alone.

What does the analysis population mean?

The Evaluable Set includes participants who received both study treatments and had a post-treatment efficacy assessment at the Exit Visit. This definition makes receipt of both interventions and availability of an assessment conditions for inclusion in the primary analysis. In general, an analysis set defined this way can differ from the enrolled population. If the included participants differ from those not included, the estimate may not represent outcomes for everyone who entered the study. The count in the Evaluable Set and the reasons some participants may not have met its criteria are not reported in the registry record.

Missing-data handling can affect an estimate when some participants lack outcome measurements. General approaches include analyzing observed outcomes, making assumptions about missing values, or using models that incorporate available measurements. Those approaches rely on different assumptions and can yield different estimates. The statistical method used to handle missing primary outcomes is not reported in the registry record, so the effect of missing data on the estimate cannot be evaluated.

How should the design shape the statistical reading?

A single-group, open-label study can describe the observed outcomes among participants receiving the treatment sequence. In general, a baseline-to-follow-up comparison does not provide the same evidence as a randomized contrast: without a concurrent comparator, changes attributable to treatment cannot be distinguished from other time-related or measurement-related changes using the group comparison alone. Lack of masking also matters for an investigator-assessed endpoint because the assessment was not blinded to treatment status. These are features of the design, not proof that the observed assessments were biased.

The record lists allocation as NA, masking as none, and the model as single-group. A randomized allocation method, a control-group analysis, and a model for estimating a comparative treatment effect are not reported in the registry record. The sponsor’s statistical analysis plan, any interim analyses, and details of endpoint-specific estimation are likewise not reported in the registry record. Those details should not be inferred from the endpoint description.

What do the planning assumptions mean?

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen design and statistical procedure. The planning illustration described for this study uses an observed effect as its reference, considers stated fractions of that effect, and assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the stated convention is to give total events; for other outcomes, it is participants per arm.

Those assumptions describe a hypothetical planning exercise, not the actual single-group study design. Planning figures are not observed power, and they do not establish that the completed study had a particular probability of detecting an effect. The numerical planning outputs and the effect fractions are not reported in the registry record. The study’s own sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 9 outcome measures and 15 analyses. The primary endpoint is the investigator-assessed ALJDS responder percentage. Secondary outcomes include mean changes in ALJDS and several FACE-Q™ measures, clinician- and patient-reported submental fat ratings, submental skin laxity, and an independent reviewer assessment of jawline definition. The numerical results for these secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes or conducts multiple analyses, the chance of at least one apparently unusual result can increase if each is assessed separately using conventional testing thresholds. Statistical methods can address this multiplicity in different ways, depending on which outcomes are confirmatory and how analyses are organized. The adjustment method, testing hierarchy, and whether any multiplicity adjustment was used are not reported in the registry record. The count of analyses alone does not establish how they were treated statistically.

The primary endpoint population is the Evaluable Set: participants who received both treatments and had a post-treatment efficacy assessment at the Exit Visit. The size of that population is not reported in the registry record. The enrollment of 58 therefore should not be assumed to be the denominator for the primary result.

Missing-data methods, reasons for missing assessments, and sensitivity analyses are not reported in the registry record. In general, incomplete follow-up can affect both the analysis denominator and the estimate if participants with missing outcomes differ from those with observed outcomes. Without the relevant counts and analytic methods, the direction or size of any such effect cannot be assessed. The registry record also does not report an intention-to-treat analysis population or define additional analysis populations beyond the primary Evaluable Set description.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: volvulus (1.9%), lower respiratory tract infection (1.9%), uterine leiomyoma (1.9%), vaginal haemorrhage (1.9%).

The registry record lists 53 participants at risk for serious adverse events, with 2 affected, and 0 deaths. For other adverse events, it lists 53 participants at risk and 53 affected. These are counts for the study group, not comparisons with an untreated or alternative-treatment group. The record does not report a comparative risk estimate.

The serious adverse event terms listed are Volvulus, Lower respiratory tract infection, Uterine leiomyoma, and Vaginal haemorrhage, each reported as 1.9%. These percentages are reproduced as recorded. The registry record does not report event timing, duration, severity beyond the serious classification, outcomes, or an assessment of whether events were related to treatment. The listed terms do not establish whether events occurred in distinct participants or whether a participant could have experienced more than one event.

As a general statistical point, adverse-event counts describe events recorded under the study’s collection and reporting procedures. They do not by themselves establish causation. In an open-label, single-group study, there is no concurrent comparison in the listed design to distinguish event frequency from what might have occurred under another condition. The record’s other-adverse-event count should also not be treated as a measure of severity: it is a separate category from the serious adverse event count.

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

The registry record describes a study asking whether participants who received sequential BELKYRA® and Juvéderm® VOLUMA™ with Lidocaine showed improvement in jawline definition by Week 58. It defines improvement as at least a 1-point change on the investigator-assessed ALJDS and identifies the analysis population and confidence-interval type. The primary percentage and confidence interval are not reported in the registry record, so the magnitude and precision of the observed primary outcome cannot be summarized.

If a responder percentage is available in another results source, its interpretation should still account for the single-group, open-label design. In general, an observed baseline-to-follow-up change describes outcomes among assessed participants, but without a concurrent comparator it cannot isolate the effect of treatment from other explanations for change. The primary population also excludes people who did not receive both treatments or did not have the specified post-treatment assessment, according to the Evaluable Set definition. How many participants met those criteria is not reported in the registry record.

The endpoint captures whether a threshold was crossed, not the full pattern or size of score changes. The separate right-side, left-side, and both-sides assessments are specified, but their results are not reported in the registry record. Secondary outcomes may add perspectives on satisfaction, submental fat, skin laxity, and independent assessment, but their results are not reported in the registry record either.

The safety entries report affected-participant counts and selected serious adverse event terms, but do not establish that an event was caused by treatment or how risk compares with another approach. Overall, the record supports a description of the study question, design, endpoint definition, and listed safety counts. It does not support a numerical conclusion about the primary response rate, its precision, or a comparative treatment effect.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how an endpoint, analysis population, and design jointly determine what a result can mean. The primary endpoint is a responder percentage based on a defined ALJDS threshold, with a specified follow-up time and a 95% confidence interval. Those details set out what the investigators intended to quantify. The result itself, however, is not reported in the registry record, so the estimate’s magnitude and uncertainty cannot be evaluated from the record.

The study also illustrates the distinction between a treatment sequence and a treatment comparison. BELKYRA® followed by VOLUMA™ was evaluated in a single-group, open-label design. Such a design can describe outcomes in the group that received the sequence, but does not provide a randomized comparison against another treatment or control. This distinction matters whenever observed change is interpreted causally.

The Evaluable Set definition is another important statistical feature. It requires receipt of both treatments and a post-treatment efficacy assessment at the Exit Visit. That makes the analysis population narrower by definition than simply referring to enrolled participants, although the actual analysis-set size is not reported in the registry record. Clear reporting of denominators and missing-data handling is essential for interpreting responder percentages.

Finally, the registry record lists multiple outcome measures and analyses, making multiplicity a relevant consideration, while not reporting the adjustment strategy. Taken together, the study record highlights why a result needs more than an outcome label: the estimate, interval, denominator, missing-data approach, and analysis plan all contribute to a sound statistical interpretation.

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 primary endpoint result and its 95% confidence interval are not reported in the registry record. The primary analysis-set size is also not reported, so the denominator for any responder percentage cannot be verified from the record. This prevents assessment of the primary estimate’s precision and the extent to which the analysis included the enrolled group.

The single-group design has no concurrent comparator, and masking is listed as none. The primary outcome was assessed by an investigator, so the unmasked design is especially relevant when considering how the measure was obtained. These characteristics limit comparative and causal interpretation, without demonstrating that the assessment was actually biased.

The registry record does not report the missing-data method, reasons for missing assessments, or sensitivity analyses. It also does not report how the 9 outcome measures and 15 analyses were handled for multiplicity. The statistical analysis plan, interim analyses, and the study’s own sample-size justification are not reported in the registry record.

The treatment description gives BELKYRA® administration details, including the maximum number and spacing of treatments, but further procedural details for VOLUMA™ are not reported in the registry record. The record’s Evaluable Set requires participants to have received both treatments and completed a post-treatment assessment. Without information on the number excluded from that set and why, the potential effect of selection into the primary analysis cannot be assessed.

For safety, the record lists counts and serious-event terms but does not report event timing, treatment relatedness, or a comparative group. The listed counts therefore describe recorded events in the study group rather than a comparative safety effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sequential Treatment With BELKYRA® Then Juvéderm® VOLUMA™ With Lidocaine for Overall Improvement in Jawline Contour — NCT03425253.
• Registry record last updated 2020-12-31; status last verified 2020-12.
• Results first posted 2020-12-31.
• 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

NCT03425253 is a completed Phase 4, prospective, open-label, single-group study sponsored by Allergan. The listed enrollment is 58, with a start date of 2018-02-02 and primary completion on 2019-12-05.

The study evaluated sequential BELKYRA® and Juvéderm® VOLUMA™ with Lidocaine treatment for jawline contour. Its primary endpoint was the percentage of participants with at least a 1-point improvement on the investigator-assessed ALJDS from Baseline (Day 0) to Week 58. The primary population was the Evaluable Set, defined by receipt of both treatments and a post-treatment efficacy assessment at the Exit Visit.

The primary result, confidence-interval limits, and analysis-set size are not reported in the registry record. Safety entries list 53 participants at risk for serious adverse events, 2 affected, and 0 deaths; for other adverse events, 53 were at risk and 53 were affected.