A Study Evaluating JUVÉDERM® VOLUMA® XC Injectable Gel for Correction of Temple Hollowing in Adult Participants ≥ 22 Years Old: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating JUVÉDERM® VOLUMA® XC Injectable Gel for Correction of Temple Hollowing in Adult Participants ≥ 22 Years Old (NCT04414397), a randomized phase 3 study. The primary outcome is Percentage of Participants With ≥ 1-grade Improvement From Baseline in the Validated Allergan Temple Hollowing Scale (ATHS) Based on Evaluating Investigator (EI) Assessment at Month 3.

2. Clinical Question

3. Trial Design

NCT04414397 is a completed Phase 3, multicenter, evaluator-blinded, randomized, parallel-group controlled study sponsored by Allergan. The registry lists an enrollment of 205 and study dates from 2020-05-28 to primary completion on 2022-10-17. The record identifies single masking and describes the study as evaluator-blinded. It does not report additional details about who besides evaluators was masked.

The two randomized groups were JUVÉDERM® VOLUMA® XC and no treatment. The primary comparison concerns the 3-month Control Period. Participants assigned to the active intervention received treatment in both temples during that period, with an optional touch-up 30 days later. Participants assigned to no treatment had no treatment during the Control Period; at Month 3, they could exit or enter the Post-Control Period, which included optional treatment and an optional touch-up.

The treatment group description also mentions an optional maintenance treatment after the initial study period. These later treatment options mean that the randomized no-treatment comparison is most directly relevant to the Control Period endpoint, rather than to an ongoing comparison of untreated and treated participants throughout later follow-up. The registry record does not report the detailed conduct of later-period comparisons.

The primary outcome was assessed at Month 3 by an Evaluating Investigator using the Allergan Temple Hollowing Scale. It was expressed as the percentage of participants whose score improved by at least 1 grade from baseline. The primary analysis population excluded randomized participants without a baseline scale score, according to the registry definition. The posted primary estimates use different denominators by group, as is also reflected in the reported endpoint results. The registry record does not report the original sample-size justification or the detailed protocol for allocation concealment.

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: Of 205 participants screened, 171 were randomized, with 113 in the treatment group and 58 in the control group. One participant was randomized to the treatment group but not treated.

Control Period

Reasons for not completing this period:

Post-Control Period

Reasons for not completing this period:

Maintenance Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat Population(mITT): all participants who were randomized and had non-missing Baseline Allergan Temple Hollowing Scale (ATHS) scores. Participants were summarized according to the randomized study intervention. Multiple imputation was used for missing data.

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: Modified Intent to Treat Population(mITT): all participants who were randomized and had non-missing Baseline Allergan Temple Hollowing Scale (ATHS) scores. Participants were summarized according to the randomized study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With ≥ 1-grade Improvement From Baseline in the Validated Allergan Temple Hollowing Scale (ATHS) Based on Evaluating Investigator (EI) Assessment at Month 3, measured over Baseline, Month 3 (Control Period).

The primary endpoint is the percentage of participants with at least 1-grade improvement from baseline on the validated Allergan Temple Hollowing Scale at Month 3, based on the Evaluating Investigator’s assessment. The scale describes temple hollowing on a 5-point range: 0 represents a convex, rounded temple, while 4 represents a severe, deeply recessed, sunken appearance. A decrease of 1 point or more is classified as improvement.

This binary endpoint reduces each participant’s score change to an indicator of whether the specified improvement threshold was met. That makes the result straightforward to express as a proportion of participants, but it does not show how large the change was for each participant or distinguish a 1-grade improvement from a larger improvement. The continuous scale information is not captured by the binary percentage alone.

An evaluator assessment provides a structured rating by an investigator using a defined scale. The evaluator-blinded design is relevant because knowledge of group assignment could influence a subjective rating. The record describes evaluator blinding, but further masking procedures are not reported in the registry record.

The Month 3 assessment takes place during the Control Period, when the randomized comparison is between treatment and no treatment. This timing supports a direct comparison of the assigned groups before the optional post-control treatment for the no-treatment group. The endpoint therefore addresses the specified scale-based improvement at that time point; it does not by itself describe longer-term outcomes or every aspect of participant experience.

7. Results Posted in the Registry

• JUVÉDERM® VOLUMA® XC: 80.5% (91/113) versus 13.8% (8/58) on control; risk difference 66.7 percentage points (95% CI 55.2 to 78.2), risk ratio 5.84 (3.05–11.18); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With a Score of "Improved " or "Much Improved" on the Global Aesthetic Improvement Scale (GAIS) for the Temple Area as Assessed by the Evaluating Investigator (EI) at Month 3

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • JUVÉDERM® VOLUMA® XC: 83.8% (88/105) versus 10.7% (6/56) on control; risk difference 73.1 percentage points (95% CI 62.4 to 83.8), risk ratio 7.82 (3.66–16.74); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for JUVÉDERM® VOLUMA® XC than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With a Score of "Improved" or "Much Improved" on the Global Aesthetic Improvement Scale (GAIS) for the Temple Area as Assessed by the Participants at Month 3

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • JUVÉDERM® VOLUMA® XC: 92.9% (92/99) versus 2.0% (1/51) on control; risk difference 91.0 percentage points (95% CI 84.6 to 97.3), risk ratio 47.39 (6.80–330.27); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for JUVÉDERM® VOLUMA® XC than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline on FACE-Q Satisfaction With Facial Appearance Questionnaire at Month 3

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • JUVÉDERM® VOLUMA® XC: mean 24.20 versus -6.60 on control; difference 30.80 (95% CI 25.79 to 35.81), standardized effect d = 1.63; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for JUVÉDERM® VOLUMA® XC than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results show a broad pattern aligned with the primary comparison: the active-treatment group had more favorable results on both Global Aesthetic Improvement Scale assessments and a more favorable change on the FACE-Q Satisfaction With Facial Appearance measure than the no-treatment group during the Control Period. This convergence across investigator-rated, participant-rated, and questionnaire outcomes adds context to the scale-based primary result, while representing different measures and perspectives.

Secondary endpoints answer related but not identical questions. The Global Aesthetic Improvement Scale asks whether the temple area was judged improved or much improved. The FACE-Q measure concerns satisfaction with facial appearance, rather than a threshold change on the temple-hollowing scale. The participant assessment is not interchangeable with the Evaluating Investigator’s rating. Agreement in broad direction can be informative, but the outcomes should not be collapsed into a single measure or assumed to carry the same evidential status.

One listed secondary outcome concerns participant satisfaction with temples, but its numerical result is not reported in the registry record. The record lists four secondary outcomes, while the posted endpoint results include estimates for three. No further endpoint result should be inferred from that listing.

Unadjusted secondary results carry less weight because the registry record does not report whether or how multiplicity was controlled. When several outcomes are examined, the chance of at least one seemingly notable result can rise. The record also does not report a full testing hierarchy or a complete statistical analysis plan. Accordingly, secondary findings are best treated as supporting, descriptive evidence that complements the prespecified primary comparison, not as independent confirmation that bypasses those limitations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With a Score of "Improved " or "Much Improved" on the Global Aesthetic Improvement Scale (GAIS) for the Temple Area as Assessed by the Evaluating Investigator (EI) at Month 3
• Percentage of Participants With a Score of "Improved" or "Much Improved" on the Global Aesthetic Improvement Scale (GAIS) for the Temple Area as Assessed by the Participants at Month 3
• Change From Baseline on FACE-Q Satisfaction With Facial Appearance Questionnaire at Month 3
• Change From Baseline to Month 3 on Participants Responses on FACE-Q Satisfaction With Temples Questionnaire

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: participants either met the threshold of at least 1-grade improvement or did not. The reported percentage is the estimated share meeting that definition in each randomized group. A group percentage is useful for describing the outcome but does not alone quantify the uncertainty in the difference between groups. The registry reports both group estimates and an analysis comparing their rates.

What does the rate difference describe?

A rate difference compares the outcome proportions in two groups by subtracting one group rate from the other, with the direction depending on the order of comparison. The registry’s primary reported estimate is a rate difference of 66.9. The unadjusted recalculation expresses the comparison as a risk difference of 0.667. The reported and recalculated estimates come from different approaches: the registry analysis used multiple imputation regression, whereas the recalculation is an unadjusted comparison based on posted summary statistics. They should not be treated as identical estimates merely because both describe a difference between groups.

Why use regression and multiple imputation?

Regression models estimate an outcome contrast while accounting for the analysis structure specified for the model. The registry identifies the primary method as multiple imputation regression but does not report the model specification, covariates, imputation model, or number of imputations. Multiple imputation is a general statistical approach for handling missing values by creating plausible completed datasets under assumptions about the missing-data process, analyzing those datasets, and combining the results to reflect both within- and between-imputation uncertainty. The registry states that it was used for missing data, but its detailed assumptions and implementation are not reported in the registry record.

The primary population is the modified Intent to Treat Population, defined as all randomized participants with non-missing baseline Allergan Temple Hollowing Scale scores. Participants were summarized according to randomized intervention. This definition retains assignment-based grouping but limits the population based on baseline scale availability. The registry does not report how many participants had missing follow-up endpoint data, the reasons for missingness, or sensitivity analyses for different missing-data assumptions.

What does a p-value contribute?

The reported primary p-value is p < 0.001. In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The record classifies the analysis as superiority. It does not report the full testing procedure or a detailed prespecified statistical analysis plan.

The unadjusted recalculation gives p < 0.001. This is a separate calculation using the posted summary statistics, not a replacement for the regression analysis. Where the registry reports an analysis for an endpoint, that analysis should be distinguished from a simple recalculation based on group summaries. Because the registry reports no discrepancy for the primary endpoint, there is no stated reason to treat the recalculation as conflicting with the reported result.

Why can variability affect continuous outcomes?

The FACE-Q Satisfaction With Facial Appearance endpoint is continuous, reported as mean change with a standard deviation. A mean describes the center of a distribution, while a standard deviation describes how spread out individual observations are around that mean. A mean difference compares group averages; it does not show the full distribution or whether every participant changed in the same direction. The posted recalculation uses the group means and standard deviations. General statistical interpretation of a mean difference also depends on assumptions about the distribution and the analysis method; the registry does not report every diagnostic or modeling detail.

For binary outcomes, the unadjusted recalculation uses the event counts and group denominators in the posted results. For continuous outcomes, it uses the reported means, standard deviations, and denominators. These recalculations are not adjusted estimates, and their p-values should not be confused with the registry’s reported analyses. In the primary analysis, the sponsor’s multiple imputation regression result is the reported inferential result.

Over-dispersion is a general concern when the observed variation in data is greater than a model assumes. If a model understates variation, standard errors may be too small and intervals may be too narrow. The primary endpoint is binary, but the registry record does not provide enough model detail to assess whether over-dispersion was evaluated or how it would have been handled. It would be inappropriate to assume a particular diagnostic, correction, or alternative model.

The primary endpoint is one of six outcome measures in the record, and four secondary outcomes are listed. Multiple testing can increase the chance of a false-positive result when many hypotheses are tested. The registry record does not report a multiplicity adjustment, a testing hierarchy for the secondary outcomes, or the full statistical plan. As a result, secondary p-values and confidence intervals should be read as endpoint-specific estimates rather than as a guaranteed family-wise confirmatory set.

11. Confidence Intervals and Precision

The primary group estimates have 95% confidence intervals: 72.7% to 88.1% for JUVÉDERM® VOLUMA® XC and 4.5% to 22.5% for no treatment during the Control Period. The reported regression analysis gives a rate difference of 66.9, with a 95% confidence interval from 54.9 to 78.8. The unadjusted recalculation gives a risk difference of 0.667, with a 95% confidence interval from 0.552 to 0.782.

A confidence interval is a range of estimates compatible with the data and the method used, under the interval’s statistical assumptions. It conveys precision: narrower intervals indicate less uncertainty in the estimate than wider intervals, all else equal. It is not a range containing every participant’s outcome, and it does not mean that each value inside the interval is equally likely. A 95% confidence interval is a property of the procedure over repeated use under its assumptions, not a guarantee about the result of a single study.

The primary group intervals are separated, and the reported interval for the rate difference is above zero. That pattern is consistent with the reported superiority result. The interval still leaves uncertainty about the size of the group contrast; estimates at the interval’s limits differ meaningfully from the point estimate. A p-value alone would not communicate that range of plausible effect sizes as directly as a confidence interval.

Precision also depends on the population and analysis. The primary groups have denominators of 58 and 113 in the posted endpoint results. The analysis uses multiple imputation for missing data, but the record does not report detailed missingness patterns or imputation assumptions. Those choices can affect uncertainty. The intervals therefore describe the reported analysis and its assumptions, not every possible analysis of the trial data.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The registry record does not report the assumptions used to plan the trial itself.

The figures are participants per arm, not total participants and not total events. The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% chance of detecting the chosen effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column gives the corresponding illustration for a higher chance of detecting that effect. Power is a property of a planned design under assumptions; it is not a probability that the observed result is true.

Rows using a smaller fraction of the observed effect require more participants per arm in these illustrations. That reflects a general feature of study planning: smaller differences are harder to distinguish from random variation, so more information is typically needed. The figures vary by endpoint because the outcomes and observed effects differ. They should not be read as observed trial power, nor as evidence that the trial was designed around the effect seen in its results. These calculations are not observed power.

The number of participants enrolled in the trial is 205, but the endpoint analysis denominators differ from enrollment. The planning illustrations do not account for every design feature that may have affected the original study, and the original design assumptions are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.138; treatment proportion p₁ = 0.805; average p̄ = 0.472.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7060 = 1.3837.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5251 = 0.4419.
4. n = (1.3837 + 0.4419)² / (0.6674)² = 7.5, rounded up to 8 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.137931034482759                          # control proportion
p1 <- 0.805309734513274                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4414397)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 8 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 14 (80% power), 18 (90% power)
 50% of observed effect: n per arm = 29 (80% power), 38 (90% power)
power.prop.test: 7.5 
Simulated power at n = 8 per arm: 0.888 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the primary comparison using multiple imputation regression: rate difference 66.9, 95% confidence interval 54.9 to 78.8, and p < 0.001. This is the sponsor’s reported analysis and is the principal inferential result for the primary endpoint.

The unadjusted recalculation from the posted group summaries gives a risk difference of 0.667, 95% confidence interval 0.552 to 0.782, and p < 0.001. It is a simpler calculation and does not reproduce the regression analysis or its multiple-imputation procedure. The estimates use different scales and methods, so close numerical correspondence should not be expected from direct comparison of their displayed values.

The registry indicates no discrepancy between the recalculation and the reported analysis. Both approaches point to a higher Month 3 improvement rate in the active-treatment group than in the control-period group. The recalculation is useful as a check on the broad pattern in the posted group summaries; it does not supersede the reported regression result, which takes precedence as the sponsor’s analysis.

Details needed to independently reproduce the sponsor’s model—including its full specification and imputation implementation—are not reported in the registry record. That limits what can be assessed about the exact adjustment and missing-data handling, even though the registry gives the method label and the primary estimate.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but it does not report a complete statistical analysis plan or a multiplicity procedure. Multiplicity refers to the statistical issue created by testing several outcomes or hypotheses. If each test is interpreted without accounting for the others, the chance of at least one false-positive result across the collection can be higher than for a single test. Adjustments or a prespecified hierarchy can address that issue, but a particular approach should not be assumed when it is not reported.

The primary result is distinguished from the secondary findings by its stated primary status and its reported multiple imputation regression analysis. The secondary estimates are informative about other outcomes, but without reported multiplicity handling their p-values should not be interpreted as if each were a standalone confirmatory test. The registry also does not state how the six outcome measures relate to a planned testing sequence or whether any outcomes were prioritized after data collection.

For missing data, the record states that multiple imputation was used for the primary endpoint. It defines the modified Intent to Treat Population as randomized participants with non-missing baseline Allergan Temple Hollowing Scale scores and says participants were summarized according to randomized intervention. The imputation model, assumptions about missingness, number of imputations, and sensitivity analyses are not reported in the registry record. Details of missing follow-up assessments and reasons for missingness are also not reported.

These omissions matter because missing-data methods rely on assumptions about why observations are absent and how the observed data relate to the missing values. Multiple imputation can incorporate uncertainty due to missing values when implemented appropriately, but its validity cannot be fully judged from the method label alone. This is a limitation on assessment of the analysis, not evidence that the method was necessarily unsuitable.

The trial’s original sample-size assumptions, interim analyses, and detailed statistical plan are not reported in the registry record. No particular interim procedure, multiplicity adjustment, or population beyond the stated modified Intent to Treat definition should be inferred.

16. 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: sinusitis (5.0%), radius fracture (2.5%), intervertebral disc degeneration (2.5%), systemic lupus erythematosus (1.9%), lung adenocarcinoma (1.9%).

The registry reports serious adverse events and other adverse events by study period and group. During the Control Period, 2 of 59 participants in the no-treatment group had a serious adverse event, and 5 of 112 participants in the JUVÉDERM® VOLUMA® XC group had a serious adverse event. The record reports zero deaths in both groups.

Additional treatment-period groupings are reported separately: in the Post-Control Period, 2 of 53 participants had a serious adverse event, and in the Maintenance Period, 4 of 40 participants had a serious adverse event. The registry also reports other adverse events for these periods, but these groupings occur at different stages and should not be treated as a single randomized comparison. Participants could receive optional treatment after the Control Period, and the record does not provide a direct randomized safety contrast across all later periods.

The registry lists serious-event terms including sinusitis, radius fracture, intervertebral disc degeneration, systemic lupus erythematosus, lung adenocarcinoma, and tooth infection, with the associated percentages recorded for those terms. A serious adverse event is not necessarily caused by the intervention; these counts alone do not establish relatedness or causation. The registry record does not provide enough information in these summaries to determine the clinical context, attribution, duration, or individual outcomes for each event.

These figures describe reported events and denominators by period. They should be read as safety reporting, not as a complete causal comparison or a basis for advice about treatment.

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

The primary result shows a clear difference between randomized groups in the proportion meeting the defined temple-hollowing improvement threshold at Month 3. The reported regression analysis estimates a rate difference of 66.9, with a 95% confidence interval from 54.9 to 78.8 and p < 0.001. The posted group estimates and the unadjusted recalculation tell a consistent broad statistical story for this endpoint and assessment period.

The result does not mean that every participant assigned to treatment improved, nor that every participant assigned to no treatment failed to improve. It does not describe the amount of change for each participant because the primary measure reduces the scale change to whether a threshold was reached. It also does not show that all participants experienced the same change or that their experiences can be predicted from the group estimate.

The evidence is bounded by the studied population, treatment schedule, outcome definition, and time point. The control group comparison applies to the 3-month Control Period; participants in the no-treatment group could receive optional treatment afterward. The Month 3 result therefore should not be interpreted as a comparison of continued treatment with continued absence of treatment over all later follow-up.

The secondary results provide additional perspectives, but multiplicity procedures and detailed analysis plans are not reported in the registry record. The safety summaries report events by period, but do not by themselves establish whether an event was caused by treatment. The registry also does not report enough detail to assess all assumptions behind the missing-data method.

Overall, the posted data describe a randomized comparison with favorable separation on the specified primary endpoint for the active-treatment group at the specified time. They do not establish outcomes beyond those measured, long-term comparative effects, or the result for an individual. They are not medical advice and should not be used as a substitute for an individualized clinical assessment.

18. Why This Trial Matters Statistically

This trial illustrates why a statistical result is more than a p-value. The primary outcome is a clearly defined binary threshold on a validated scale, with group percentages, confidence intervals, a reported regression estimate, and an unadjusted recalculation. Considering these together shows both the direction of the group contrast and the uncertainty around its size.

The randomized, parallel-group comparison is most interpretable during the Control Period, before optional post-control treatment changes the treatment contrast. The primary assessment at Month 3 aligns with that period. Recognizing the timing prevents later optional treatments and follow-up from being mistaken for a continued randomized comparison of treatment against no treatment.

The record also demonstrates that reported and recalculated estimates are not interchangeable. A multiple imputation regression analysis addresses the primary outcome using a specified method label, while an unadjusted calculation from group summaries is a simpler check. Knowing which estimate comes from the registry’s analysis—and which is a recalculation—matters when interpreting the result.

Finally, the case highlights the value of transparent reporting. The record provides the population definition and says multiple imputation was used, but does not describe the imputation model, multiplicity handling, or original sample-size assumptions. Such details affect how fully readers can evaluate precision and robustness. Statistical interpretation therefore combines the result with careful attention to what the registry does and does not report.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary estimate is based on the modified Intent to Treat Population, which requires a non-missing baseline scale score. The registry states that multiple imputation was used for missing data, but does not report the imputation model, missingness assumptions, or sensitivity analyses. Readers therefore cannot fully assess the robustness of the primary estimate to alternative missing-data assumptions.

The record does not report a complete statistical analysis plan, including multiplicity handling for secondary outcomes or a testing hierarchy. This makes the secondary results less secure as confirmatory evidence. It also does not report the trial’s original sample-size justification or interim-analysis procedures; planning illustrations based on observed effects cannot fill those reporting gaps.

The primary outcome is a threshold measure. It records whether a participant improved by at least 1 grade, not the full distribution of scale changes or the degree of improvement among participants. The evaluator assessment is structured and the study is described as evaluator-blinded, but further details about masking procedures and their maintenance are not reported in the registry record.

The randomized comparison is specific to the 3-month Control Period. Participants assigned to no treatment could exit at Month 3 or receive optional treatment afterward, and the active-treatment group could receive optional maintenance later. Later-period safety summaries involve different groups and exposure periods; they are not equivalent to a continued randomized comparison. The registry does not report enough information to assess long-term comparative outcomes.

Finally, registry summaries do not provide full participant-level data, all model details, or contextual information for individual adverse events. The posted results support interpretation of the stated outcomes and periods, but do not answer questions beyond those recorded.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study Evaluating JUVÉDERM® VOLUMA® XC Injectable Gel for Correction of Temple Hollowing in Adult Participants ≥ 22 Years Old — NCT04414397.
• Registry record last updated 2024-04-25; status last verified 2024-03.
• Results first posted 2024-04-25.
• 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.

23. Record Summary

NCT04414397 is a completed Phase 3 randomized, parallel-group controlled study of JUVÉDERM® VOLUMA® XC for correction of temple hollowing in adults. The primary endpoint was the percentage of participants with at least 1-grade improvement on the Allergan Temple Hollowing Scale at Month 3, assessed by an Evaluating Investigator. The reported multiple imputation regression analysis found a rate difference of 66.9, with a 95% confidence interval from 54.9 to 78.8 and p < 0.001.

The registry also posts secondary aesthetic and FACE-Q outcomes and safety summaries organized by study period. The record does not report a complete statistical analysis plan, multiplicity procedures, original sample-size justification, or detailed multiple-imputation assumptions. Results should be interpreted within the stated population, endpoint, and Control Period comparison.