Safety and Effectiveness of JUVÉDERM VOLUMA® XC Injectable Gel for Correction of Temple Hollowing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of JUVÉDERM VOLUMA® XC Injectable Gel for Correction of Temple Hollowing (NCT03166618), a randomized na study. The primary outcome is Percentage of Participants With at Least a 1-Point Improvement (Decrease) in Both Temples as Assessed by the Evaluating Investigator Using the Allergan Temple Hollowing Scale (ATHS).

2. Clinical Question

3. Trial Design

NCT03166618 was registered as a randomized, single-blind, parallel-group controlled study. Its official title describes a multicenter study, and the registry lists the phase as NA. The sponsor was Allergan. The study began on 2017-04-24, had a primary completion date of 2017-07-21, and is listed as terminated.

The planned comparison was between JUVÉDERM VOLUMA XC injectable gel and no treatment. The treatment description specified injection in both temples, with eligibility for touch-up treatment 30 days later. The control description specified that no treatment would be administered. These are protocol descriptions, not evidence that treatment took place: the primary outcome population note states that no treatment was administered and no analyses were conducted.

The record says up to 189 subjects were planned and that 1 subject was enrolled in the control No Treatment arm. No participant is reported as enrolled in the treatment arm. The planned randomized comparison therefore did not yield analyzed outcome data for comparing the arms. The record does not explain why the study was terminated, whether recruitment was attempted beyond the enrolled participant, or whether any assessments were collected before termination.

Single-blind indicates that the study was designated as having one level of masking, but the identity of the masked parties and the procedures used to maintain masking are not reported in the registry record. Randomization methods, allocation concealment, site counts, and the timing or conduct of any interim review are also not reported. These details cannot be inferred from the design labels alone.

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.

Before assignment: Up to 189 subjects were planned; 1 subject was enrolled but did not receive treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Up to 189 subjects were planned; 1 subject was enrolled in the control\_No Treatment arm. Terminated study; no treatment was administered and no analyses were conducted.

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: Up to 189 subjects were planned; 1 subject was enrolled in the control\_No Treatment arm. Due to confidentiality considerations, baseline data is not being provided to protect participant privacy.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least a 1-Point Improvement (Decrease) in Both Temples as Assessed by the Evaluating Investigator Using the Allergan Temple Hollowing Scale (ATHS), measured over Change from Baseline to Month 3.

The primary endpoint was the percentage of participants with at least a 1-point improvement, defined as a decrease, in both temples according to the evaluating investigator using the Allergan Temple Hollowing Scale (ATHS). The planned assessment window was change from baseline to Month 3. The ATHS is described as a 5-point scale, ranging from 0 for a convex, rounded temple to 4 for a severe, deeply recessed, sunken appearance. On that scale, a decrease of at least one point was designated as improvement.

In general, a scale-based endpoint can translate a change in a measured feature into a defined response category. Requiring improvement in both temples makes the response criterion depend on each side meeting the specified threshold, rather than on an average across the two sides. The investigator assessment supplies the endpoint rating; it does not itself establish how consistently different investigators would score the scale. The registry record does not report validation or reliability information for the ATHS.

The endpoint is a binary responder measure: a participant either meets the stated improvement criterion or does not. Reporting a percentage would ordinarily require both a defined analysis population and observed response data. Neither an endpoint result nor an analysis population is reported in the registry record. With no treatment administered and no analyses conducted, the planned endpoint cannot be interpreted as an observed treatment response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study was designed as a randomized, parallel-group comparison. In general, random allocation is intended to reduce systematic differences between groups at entry, while a parallel-group design assigns participants to one study arm for comparison. These design features support a causal comparison only when treatment assignment, follow-up, outcome measurement, and analysis are adequately carried out. The registry record does not report the randomization sequence, allocation concealment, or analysis procedures. Its design labels alone do not establish how those procedures were implemented.

The primary endpoint is a binary responder outcome. The response rule was an investigator-assessed decrease of at least one ATHS point in both temples between baseline and Month 3. For a binary outcome, a group percentage is generally calculated from the number of participants meeting the response definition and the number included in the defined analysis population. A comparison might then estimate a difference or another contrast between groups. The registry record contains no responder counts, denominators for this endpoint, effect estimate, or analysis population, so no such quantity can be interpreted for this study.

In general, an estimate and its confidence interval are more informative together than a result label alone. The estimate describes the magnitude and direction of an observed contrast, while the interval conveys the range of values compatible with the data under the analysis assumptions. A narrow interval generally indicates greater precision than a wide interval. Neither an interval nor an estimate is reported for the primary outcome. There is therefore no basis for judging the precision of a treatment comparison.

A p-value, in general, describes how compatible the observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. The registry record reports zero analyses and no p-value. It also does not report a prespecified statistical analysis plan, the null hypothesis, covariate adjustment, or a method for handling potential departures from model assumptions. None of these choices can be reconstructed from the endpoint description.

The posted planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect specified as a fraction of an observed effect. They also distinguish participants per arm for most outcomes from total events for time-to-event outcomes. These are planning conventions, not observed trial statistics. The record does not report a trial-specific sample-size justification or the inputs needed to interpret an actual sample-size calculation. In particular, the illustration does not amount to observed power or a substitute for outcome data.

In general, power is a design-stage probability of detecting an effect of a specified size under stated assumptions. It is not a measure of whether a completed study has proved a hypothesis, and calculating power after the fact from an observed result does not resolve uncertainty. No outcome analysis was conducted according to the registry record, so there is no observed effect on which to base a trial-specific assessment of power. No interim analyses or stopping rules are reported.

Blinding can reduce certain risks of bias if the people whose expectations might influence treatment or outcome assessment are masked. The registry design is labeled single-blind, but the record does not identify who was masked or describe procedures for preserving masking. Since the primary endpoint relies on an investigator rating, information about assessor masking would be relevant to interpreting that measurement; it is not reported. No inference about successful masking is possible from the label alone.

More generally, when count data show greater variability than a model assumes, methods that account for over-dispersion may be needed to avoid overstating precision. That issue cannot be evaluated from this record: no count outcome analysis or model is reported, and the primary endpoint is specified as a binary participant response. It would be inappropriate to claim that any particular model, correction, or variance assumption was used.

The record lists secondary GAIS outcomes assessed by the investigator and participant. When several outcomes or comparisons are analyzed, multiplicity can increase the chance of at least one apparently notable finding. Statistical plans may address this through a hierarchy or an adjustment, but none is reported. Because no analyses were conducted, there are no secondary comparisons to interpret and no reported multiplicity procedure.

Missing-data methods depend on what was measured, why observations are missing, and the analysis objective. General approaches can include explicit assumptions, imputation, or sensitivity analyses, but their appropriateness cannot be determined without the data and a prespecified plan. The registry record does not report missing outcome counts, reasons for missingness, or any missing-data method. It also does not identify intention-to-treat, per-protocol, or other analysis populations. These omissions prevent assessment of how participants would have been included in an efficacy analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary GAIS outcomes: the percentage rated Improved or Much Improved by the evaluating investigator, and the corresponding percentage based on participant assessment. Listing multiple outcomes makes it relevant to know whether the analysis plan established a hierarchy or addressed multiplicity. The registry record does not report a multiplicity strategy. However, it also states that no analyses were conducted, so there are no reported outcome tests or estimates whose interpretation would depend on such a procedure.

The record does not report the number of missing outcome assessments, reasons for missingness, or how missing values would have been handled. It also does not specify an analysis population, such as all randomized participants or participants with an observed Month 3 assessment. The planned endpoint requires a baseline-to-Month 3 comparison and a qualifying improvement in both temples; how incomplete measurements would have been classified is not reported.

In general, missing-data handling can affect both the estimated response rate and the uncertainty around it. Complete-case analysis, imputation, or sensitivity analyses rely on different assumptions and can yield different interpretations. Without an analysis plan, participant-level outcome information, and a description of missingness, the suitability of any approach cannot be evaluated. None should be attributed to this trial.

The record identifies 1 enrolled participant in the control No Treatment arm and says no treatment was administered and no analyses were conducted. It does not provide further information about follow-up or outcome completion. The appropriate conclusion is that analysis populations, missing-data handling, and multiplicity procedures are not reported in the registry record, rather than assuming that any particular method was used.

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.

The adverse-event group listings report zero participants at risk for serious adverse events and zero at risk for other adverse events in the VOLUMA XC Treatment arm. For the Control No Treatment arm, the listings report 1 participant at risk for serious adverse events and 1 at risk for other adverse events. The listed counts affected are zero for serious and other adverse events in both groups, and deaths are listed as zero in both groups.

These are the registry’s reported figures, not a comparative safety analysis. The treatment arm had no participant reported at risk, and the record states that no treatment was administered. Therefore, its zero event counts do not describe an observed safety experience after exposure to the injectable gel. In the control arm, the listed zero affected counts describe the registry entry, but the record does not provide event definitions, event-collection procedures, follow-up completeness, or a detailed safety analysis.

In general, a count of zero reported events does not establish that an intervention is free of risk. Interpretation depends on the number and characteristics of participants exposed, observation time, completeness of reporting, and how events were defined and collected. Those details are not reported sufficiently to support a safety comparison or a conclusion about treatment-related risk.

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

The central result of this registry record is the absence of an analyzed efficacy result. The study was intended to assess whether JUVÉDERM VOLUMA XC treatment was associated with at least a 1-point decrease on the ATHS in both temples from baseline to Month 3. The record states that the study was terminated, no treatment was administered, and no analyses were conducted. It does not report whether any participant met the endpoint.

This means the trial does not provide an estimate of the planned treatment effect or its precision. It does not show how the treatment group compared with the no-treatment control, and it cannot establish that either group improved or failed to improve. A missing analysis is not a null finding: it is not equivalent to a measured effect of zero, a nonsignificant result, or evidence of no difference.

The design and endpoint descriptions still clarify the question investigators intended to study. The planned treatment was administration to both temples, with eligibility for touch-up after 30 days. The primary measurement was an investigator rating, and the secondary outcomes involved GAIS ratings by the investigator and participant. These descriptions explain the planned assessment framework; they are not outcome findings.

The safety listings also should not be mistaken for a treatment safety result. No participant is reported at risk in the treatment arm, and the registry says treatment was not administered. The zero event counts in that arm therefore cannot be used to characterize events following treatment exposure. The control listing does not provide a randomized safety comparison.

More broadly, the record does not explain the reason for termination, report a statistical analysis plan, or describe outcome completion and missing-data handling. Without those details and outcome data, no estimate can be recovered from the study description. The appropriate interpretation is limited: the registry documents a planned randomized comparison that did not generate reported analyses addressing its clinical question. It neither demonstrates benefit nor demonstrates lack of benefit.

13. Why This Trial Matters Statistically

This trial matters statistically because its design labels and planned endpoints can look like the basis for a comparative result, while the registry record reports that the comparison was never analyzed. Recognizing the distinction between a protocol question and an observed result is essential. A randomized design can support a meaningful comparison when groups are enrolled, outcomes are measured, and an analysis is performed; those elements cannot be presumed from the registration alone.

The endpoint also illustrates how a clinical concept is operationalized. Temple hollowing was represented by an investigator-rated ATHS score, and improvement was defined as a decrease of at least one point in both temples. Such a threshold creates a clear responder definition, but a definition is not evidence that responses occurred. To evaluate the endpoint statistically, readers would need the responder data, denominators, and a comparison with an uncertainty estimate. The record reports none of these.

The enrollment information is important for interpreting what can be learned. Up to 189 subjects were planned, while 1 subject was enrolled in the control No Treatment arm. The record reports no treatment administration and no analyses. That is fundamentally different from a completed study with imprecise estimates: in this case, the planned treatment contrast is not reported at all.

The case also shows why zero adverse-event counts must be read alongside exposure and follow-up. A treatment group with no participant reported at risk cannot provide an observed post-treatment safety profile. Event counts alone, without exposure and ascertainment context, are not a comparative safety estimate.

Finally, the record’s planning assumptions should not be confused with a completed analysis or with evidence about the original design rationale. Statistical interpretation depends on the data actually collected and the methods actually used. Here, the record’s most consequential statistical fact is that no analyses were conducted, leaving the planned efficacy and safety comparisons unanswered.

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 principal limitation is that the registry record reports no analyses. There is no primary endpoint result, no secondary outcome result, and no estimate comparing treatment with no treatment. The efficacy question is therefore unanswered, rather than answered imprecisely or with a null finding.

The enrollment record further limits interpretation: up to 189 subjects were planned, but 1 subject was enrolled in the control No Treatment arm. No treatment was administered. The registry provides no analyzed treatment-exposed group, so it cannot inform the effect of treatment or describe safety after exposure.

The reason for termination is not reported in the registry record. It also does not explain whether assessments were collected, whether follow-up was completed, or whether any unreported data exist. These uncertainties cannot be resolved from the posted record and should not be filled in by speculation.

Important design and analysis details are not reported, including the randomization procedure, allocation concealment, the identity of masked parties, the statistical analysis plan, analysis populations, missing-data methods, and any multiplicity approach. The record also does not report ATHS reliability information or detailed outcome measurement procedures. These limitations prevent evaluation of how the planned analysis would have addressed bias, uncertainty, and incomplete data.

The adverse-event listings have limited interpretability because no participant is reported at risk in the treatment group and no treatment was administered. The record does not describe event definitions, ascertainment, or follow-up in enough detail to support a safety comparison. Overall, the available information describes the intended study and its termination, but not clinical outcome evidence from a completed comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Effectiveness of JUVÉDERM VOLUMA® XC Injectable Gel for Correction of Temple Hollowing — NCT03166618.
• Registry record last updated 2018-10-18; status last verified 2018-10.
• Results first posted 2018-10-18.
• 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

NCT03166618 was a randomized, single-blind, parallel-group controlled study sponsored by Allergan, with phase listed as NA. It planned to evaluate JUVÉDERM VOLUMA XC injectable gel for correction of temple hollowing against a no-treatment control. The treatment description specified both temples and eligibility for touch-up treatment 30 days later.

The planned primary endpoint was the percentage with at least a 1-point decrease in both temples on the investigator-assessed ATHS from baseline to Month 3. Secondary outcomes were GAIS improvement ratings by the evaluating investigator and participant. Up to 189 subjects were planned, and 1 subject was enrolled in the control No Treatment arm. The study is listed as terminated; the record states no treatment was administered and no analyses were conducted.

Accordingly, no efficacy comparison or analyzed safety result is reported. The reason for termination, analysis populations, missing-data methods, and statistical analysis plan are not reported in the registry record.