A Clinical Study to Evaluate the Efficacy and Safety of YVOIRE Volume Plus Versus YVOIRE Volume in Nasolabial Fold Injection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Study to Evaluate the Efficacy and Safety of YVOIRE Volume Plus Versus YVOIRE Volume in Nasolabial Fold Injection (NCT02340078), a randomized na study. The primary outcome is Proportion of the Subjects With at Least 10mm Difference in VAS Pain Scale Scores Within the Subject (VAS of the Control Device - VAS of the Test Device) Immediately After Treatment With the Investigational Devices.

2. Clinical Question

This question is specifically about an immediate pain-score contrast within the subject. It is not a question about longer-term wrinkle appearance, duration of effect, or safety over an extended follow-up period. The registry lists one primary outcome measure, with its timeframe at Visit 2 (week 0, immediately after treatment). The record does not state a separate primary question about changes in appearance or patient satisfaction.

3. Trial Design

The study is listed as randomized, triple-masked, active-controlled, and completed. Its official title describes a randomized, multi-center, double-blind, matched-pairs design; the masking field separately records triple masking. The study model field is listed as SINGLE GROUP. These labels do not, by themselves, provide a full account of how allocation, masking, or the paired comparison was implemented.

The comparison involved HA IDF II plus, a cross-linked HA filler with lidocaine, and HA IDF II, a cross-linked HA filler without lidocaine. The registry's brief summary says the objective was to evaluate efficacy and safety of the product with lidocaine compared with the product without lidocaine in nasolabial fold injection. The official title refers to HA IDF II Plus and HA IDF II, while the intervention entries use HA IDF II plus and HA IDF II.

Enrollment is recorded as 62. The outcome categories each show a denominator of 62: 59 subjects had at least a 10mm difference in VAS, and 3 had a difference below 10mm. These are outcome-category counts, not separate product-arm sizes. The registry does not give product-specific group sizes in the posted outcome entries.

The listed study start is 2013-11, and primary completion is 2015-02. The study status is completed. Phase is recorded as NA, and LG Life Sciences is the sponsor. Details such as the exact allocation sequence, the number of clinical centers, the timing and roles of masking, and the original sample-size justification are not reported in the registry record.

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: spilt-face design. Subjects were decided by randomization which side of the face would be injected with the test device. According to this randomization result, the other side would be determined to be injected with a comparator. It was determined just by one randomization.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of the Subjects With at Least 10mm Difference in VAS Pain Scale Scores Within the Subject (VAS of the Control Device - VAS of the Test Device) Immediately After Treatment With the Investigational Devices, measured over Visit 2 (week 0, immediately after treatment).

The primary endpoint is the proportion of subjects with at least a 10mm difference in VAS pain scores within the subject, calculated as the control-device VAS score minus the test-device VAS score. The assessment is described as taking place immediately after treatment with the investigational devices, at Visit 2 (week 0). Pain was evaluated with a visual analog scale, measuring the length from the left end to the subject's mark in millimeters.

This endpoint turns the paired pain-score comparison into a binary outcome: a subject either meets the at-least-10mm threshold or has a difference below that threshold. A threshold can make a result easier to interpret as the frequency of subjects experiencing a difference of a specified size, but it discards information about how far each subject's score lies above or below the cutoff. Subjects with differences of very different magnitudes may therefore fall into the same category.

The endpoint is suited to the immediate pain comparison described by the study objective. It does not measure pain over time, other aspects of tolerability, or longer-term clinical outcomes. The registry record does not explain why the 10mm threshold was selected, whether it had been established before the study, or how missing VAS assessments were handled.

7. Results Posted in the Registry

• Subjects With Below 10mm Difference in VAS: 4.8% (3/62) versus 95.2% (59/62) on control; risk difference -90.3 percentage points (95% CI -97.9 to -82.8), risk ratio 0.05 (0.02–0.15); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each subject is classified into one of two outcome states. In this study the states are having at least a 10mm within-subject difference in VAS and having a difference below 10mm. A count in each state is meaningful only alongside its denominator: the count indicates how many observations were assigned to the category, while the denominator indicates how many observations were represented for that category. The registry lists 59 and 3, with 62 recorded for each category.

What does the risk difference represent?

A risk difference subtracts one event proportion from another. It is expressed on the proportion scale, and its sign depends on which group or outcome category is subtracted from which. In the recalculation, the compared categories are the subjects below the threshold and those meeting it. The resulting estimate, -0.903, therefore describes the contrast between those endpoint categories as represented in the posted counts. It is not a product-arm treatment effect, because the registry entries do not identify these categories as randomized groups.

For a comparison intended to estimate a treatment effect, the groups in the calculation need to correspond to the relevant treatment assignments or to a suitable paired analysis. In this record, the endpoint itself is within-subject: each subject's control-device score is subtracted from the test-device score. A paired analysis uses the relationship between measurements from the same subject. Treating the two endpoint categories as if they were independent treatment arms answers a different statistical question. That is why the recalculated category contrast must be interpreted separately from the sponsor's reported proportion.

How should the p-value be read?

A p-value describes how incompatible the observed data are with a specified statistical null model, under the assumptions of the test. The recalculated p <0.001 pertains to the category contrast used in that recalculation. It does not measure the probability that the null hypothesis is true, the probability that the finding is due to chance, or the size of a clinical effect. It also does not replace the study's paired analysis. The registry does not report a p-value for the sponsor's analysis.

Statistical significance and effect size answer different questions. A test can indicate evidence against a null model, while an estimate and confidence interval describe the direction and range of values compatible with the data under the method. Neither alone establishes the importance of an endpoint or resolves limitations in how the comparison was recorded.

Why does the paired structure matter?

When two measurements come from the same subject, they tend to share characteristics of that subject. A paired comparison focuses on within-subject differences and accounts for that linkage. The endpoint title explicitly defines a control-device score minus a test-device score within the subject, and the official title describes a matched-pairs design. The record does not provide the individual paired scores or the precise statistical method used by the sponsor, so the paired result cannot be reconstructed from the category counts alone.

The endpoint also dichotomizes a continuous VAS difference at 10mm. Dichotomizing can make a threshold-based result accessible, but it loses information about the spread and exact sizes of the differences. A subject just above the cutoff and one with a much larger difference contribute alike to the threshold count. The posted result does not show how close individual observations were to the cutoff.

What do the intervals communicate?

A confidence interval describes uncertainty around an estimate under the statistical method used. The sponsor reports a 95% confidence interval from 0.87 to 0.99 around the proportion 0.952. The recalculated risk difference has an interval from -0.979 to -0.828. These intervals correspond to different statistical summaries, so they should not be compared as though they estimate the same quantity. An interval is not a guarantee that the true value lies within its limits, nor does it address bias, outcome definition, or missing data.

Counts and intervals are affected by the analysis population and the handling of incomplete observations. The registry does not state the analysis population, whether all enrolled subjects contributed to the primary endpoint, or how unavailable VAS measurements were treated. It also does not report the sponsor's detailed modeling or testing method. Those omissions limit independent reconstruction and make it important to keep the reported sponsor result distinct from the unadjusted recalculation.

General statistical interpretation also depends on prespecification. A test and interval are most informative when the endpoint, analysis population, and method were established before results were examined. The protocol's statistical plan, sample-size justification, interim-analysis procedures, and multiplicity strategy are not reported in the registry record. They should not be inferred from the posted endpoint counts or from the recalculated p-value.

10. Confidence Intervals and Precision

The sponsor's reported estimate for the proportion of subjects with at least a 10mm VAS difference is 0.952. Its 95% confidence interval extends from 0.87 to 0.99. The interval communicates uncertainty in the estimated proportion under the sponsor's analysis method. It does not mean that the estimate is free from bias, and it does not cover uncertainty about the choice of endpoint or the handling of missing observations.

The separate unadjusted recalculation reports a risk difference of -0.903, with a confidence interval from -0.979 to -0.828. This interval relates to the contrast between the two recorded endpoint categories, not a treatment-effect estimate comparing randomized product groups. The categories are based on the same within-subject endpoint definition, and the posted result does not include the subject-level paired scores needed to reconstruct the sponsor's paired analysis.

Confidence intervals are most useful when read together with the quantity being estimated and the analysis that generated it. The sponsor interval concerns a proportion; the recalculated interval concerns a risk difference. Their endpoints should not be treated as interchangeable descriptions of one estimate. The record does not report a confidence interval for the mean or distribution of the paired VAS differences, nor does it give confidence intervals for other clinical outcomes.

Precision is also distinct from clinical importance. The registry does not explain the basis for the 10mm threshold, and the interval cannot establish whether the threshold represents a clinically meaningful difference. The posted interval concerns the immediate assessment at Visit 2 (week 0); it does not quantify uncertainty at later time points.

11. 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 planning figures are participants per arm, not total participants or total events. They are illustrations based on the observed effect, rather than the original design calculation for this study. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 4 participants per arm for 80% power and 4 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 7 participants per arm for 80% power and 9 participants per arm for 90% power. For planning for 50% of the observed effect, the figures are 15 participants per arm for 80% power and 19 participants per arm for 90% power. The curve visualizes these planning scenarios rather than reporting observed enrollment needs for a future study.

In plain language, the 80% power column gives the planned number per arm under the stated assumptions for a design intended to detect the chosen effect with 80% power. The 90% column gives the corresponding planning number for a design intended to detect it with 90% power. Higher planned power generally requires a larger sample under otherwise similar assumptions, and smaller effects need more participants to detect.

These figures are not observed power. They are planning illustrations computed from the observed effect, not evidence about the adequacy of this completed trial's original design. The original sample-size assumptions and justification are not reported in the registry record. The planning table does not resolve the separate limitation that the posted recalculation contrasts endpoint categories rather than randomized product groups.

12. 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 = 0.952; treatment proportion p₁ = 0.048; average p̄ = 0.500.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7071 = 1.3859.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3035 = 0.2554.
4. n = (1.3859 + 0.2554)² / (-0.9032)² = 3.3, rounded up to 4 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 <- 0.951612903225806                          # control proportion
p1 <- 0.0483870967741935                          # 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(2340078)
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 = 4 (80% power), 4 (90% power)
 75% of observed effect: n per arm = 7 (80% power), 9 (90% power)
 50% of observed effect: n per arm = 15 (80% power), 19 (90% power)
power.prop.test: 3.3 
Simulated power at n = 4 per arm: 0.946 (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.

13. Analyses Reported by the Sponsor

The sponsor's reported analysis gives a proportion of 0.952 for subjects with a VAS difference of at least 10mm and a 95% confidence interval from 0.87 to 0.99. The registry labels that analysis as superiority. It does not report a p-value or identify the statistical method used for that analysis.

The recalculation uses the posted counts to contrast the at-least-10mm category with the below-10mm category. It reports a risk difference of -0.903 and p <0.001, along with an interval from -0.979 to -0.828. This is an unadjusted recalculation from the summary counts. It is not a reanalysis of subject-level paired VAS measurements and should not be presented as an independent estimate of the product comparison.

The two summaries answer different statistical questions: the sponsor reports the threshold proportion, while the recalculation contrasts the recorded outcome categories. The sponsor's analysis is the relevant posted analysis for the primary endpoint. The registry record does not provide enough detail to reproduce its method or verify how it accounted for the matched-pairs structure.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis, with no secondary outcomes posted. This is the extent of the available outcome listing; it does not establish how many outcomes or analyses were prespecified in the protocol, or whether additional analyses were conducted but not posted. The analysis plan is not reported in the registry record.

Multiplicity arises when several outcomes, time points, or statistical tests are examined. Without a prespecified strategy, repeated testing can increase the chance that at least one result appears notable by chance. The record does not report whether any adjustment for multiple comparisons was planned or used. It also does not report interim analyses or stopping rules. Neither should be inferred from the single posted primary result.

The analysis population for the primary endpoint is not reported in the registry record. Although enrollment is listed as 62 and each outcome category has a denominator of 62, the record does not say whether the analysis followed an intention-to-treat, per-protocol, or other population definition. It does not specify exclusions, protocol deviations, or whether the recorded denominator represents all randomized subjects or only subjects with an available assessment.

Missing-data handling is also not reported in the registry record. The outcome entries do not explain whether any VAS values were missing, how missing values were treated, or whether sensitivity analyses were conducted. These details matter because the estimate depends on which observations contribute to the endpoint and how incomplete observations are handled.

The registry describes a randomized and matched-pairs study, but it does not give the statistical analysis plan, the sponsor's detailed method, or the subject-level paired data. These omissions prevent independent confirmation that the posted analysis fully reflects the planned paired comparison. They also limit conclusions about robustness to alternative missing-data or analysis-population choices.

15. 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 4% reporting threshold.

Most frequent non-serious adverse event terms

The safety entry lists 62 subjects at risk for serious adverse events and records 0 serious adverse events affecting them. For other adverse events, the entry lists 62 at risk and 3 affected. These are separate registry summaries; the record does not provide event terms for the other adverse events in this entry.

The serious adverse event count is not a complete description of safety. It does not indicate the severity or type of the other adverse events, their timing, whether they were considered related to treatment, or how long subjects were followed for safety. The top serious adverse event terms field is empty. Deaths are not reported in the registry record.

These figures should be read in the context of the study record and its listed safety population. The record does not provide further detail about the safety analysis population, event definitions, follow-up duration, or comparative safety by product. The counts alone do not establish that no other safety concerns occurred.

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

The primary result concerns the immediate within-subject VAS pain-score difference after treatment. The registry reports that 59 subjects met the at-least-10mm threshold and 3 were below it, with 62 recorded in each category. The sponsor reports a proportion of 0.952 and a 95% confidence interval from 0.87 to 0.99 for the threshold outcome. These figures describe the posted binary endpoint at Visit 2 (week 0).

The endpoint is defined as control-device VAS minus test-device VAS. Its direction therefore depends on the order of that subtraction, and interpretation requires care about which device is designated control and which test. The brief summary describes the comparison as HA IDF II plus with lidocaine versus HA IDF II without lidocaine, but the posted result does not provide the paired VAS values. The category counts alone do not show the magnitude or distribution of individual differences.

The finding does not establish effects on longer-term appearance, durability, pain at later visits, or outcomes not posted in the registry. It also does not by itself establish comparative safety. The safety record reports 0 serious adverse events and 3 other adverse events, but provides limited detail about event type and follow-up.

The recalculated risk difference and p-value should not be interpreted as a randomized treatment comparison: they arise from contrasting the recorded threshold categories. The sponsor's posted proportion is the more directly aligned summary of the binary endpoint, while the detailed method and analysis population are not reported in the registry record.

Statistical estimates are not substitutes for the clinical context needed to judge the significance of a threshold or the relevance of a short-term pain measure. This result characterizes the posted endpoint in this completed study; it does not establish that either product works or does not work, and it should not be generalized beyond the population and assessment described in the registry record.

17. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a paired endpoint and a two-group summary. The primary endpoint is explicitly a within-subject difference in VAS scores, and the official title describes a matched-pairs design. Yet the posted counts are organized as categories according to whether the difference reaches a threshold. Reading those counts as if they were two independent treatment arms would change the question being answered.

The recalculation illustrates why the estimand—the exact quantity a statistical analysis aims to estimate—must be identified before interpreting a risk difference or p-value. Here, the recalculated contrast is between the endpoint categories. The sponsor's report instead gives the threshold proportion. Without subject-level paired measurements and fuller methods, the posted summary cannot support reconstruction of a paired treatment-effect analysis.

The endpoint also shows the trade-off in converting a continuous measure into a binary threshold. A threshold can communicate the frequency of a defined response, but it suppresses information about the size and spread of observed differences. Reporting both threshold results and an appropriate summary of the paired continuous differences can offer a fuller account, though the registry does not post those additional summaries.

Finally, precision should be judged for the specific estimate and analysis that generated it. The sponsor's confidence interval and the recalculated interval refer to different quantities. Keeping those quantities distinct, while noting the unreported analysis plan and missing-data procedures, helps prevent a numerically striking contrast from being mistaken for evidence about a different question.

18. 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 registry does not provide the individual paired VAS scores, their distribution, or detailed results for the two device measurements. As a result, the sponsor's paired comparison cannot be independently reconstructed from the posted category counts. The recalculated category contrast is not a substitute for that analysis.

The endpoint is dichotomized at 10mm. The record does not explain how the threshold was selected or whether it was prespecified. Because the posted result only classifies subjects above or below the cutoff, it does not show how far observations were from the threshold or summarize the full range of VAS differences.

The original sample-size justification, the statistical analysis plan, the analysis population, and missing-data procedures are not reported in the registry record. The exact allocation and masking procedures are also not described in detail. Although the study is labelled randomized and triple-masked and its official title describes a matched-pairs design, those labels do not resolve these methodological details.

Only one outcome measure and one analysis are listed, and no secondary outcomes are posted. The registry does not state whether other outcomes were planned, whether interim analyses were conducted, or how multiplicity was addressed. Safety reporting is also limited: event terms and deaths are not detailed, and the safety follow-up duration is not reported in the registry record.

The primary assessment is immediate after treatment at Visit 2 (week 0). The posted endpoint therefore does not address later pain assessments or longer-term outcomes. These limitations constrain what can be concluded from the registry result, even when its reported estimate and interval are read as stated.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Clinical Study to Evaluate the Efficacy and Safety of YVOIRE Volume Plus Versus YVOIRE Volume in Nasolabial Fold Injection — NCT02340078.
• Registry record last updated 2019-01-23; status last verified 2013-11.
• Results first posted 2019-01-23.
• 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.

22. Record Summary

NCT02340078 is a completed, randomized, triple-masked, active-controlled study of HA IDF II plus, a cross-linked HA filler with lidocaine, compared with HA IDF II, a cross-linked HA filler without lidocaine, for nasolabial fold injection. The official title describes a matched-pairs design. Enrollment is 62, the listed start is 2013-11, and primary completion is 2015-02.

The primary endpoint is the proportion of subjects with at least a 10mm within-subject difference in VAS pain scores immediately after treatment, defined as control-device score minus test-device score. The posted categories include 59 subjects meeting the threshold and 3 below it. The sponsor reports a proportion of 0.952 with a 95% confidence interval from 0.87 to 0.99.

The recalculated contrast is between the two outcome categories, not randomized product groups. Details of the paired analysis, missing data, analysis population, and original sample-size rationale are not reported in the registry record.