Evaluation of Pain With Radiesse® With Lidocaine for Nasolabial Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Pain With Radiesse® With Lidocaine for Nasolabial Folds (NCT01069354), a randomized na study. The primary outcome is Pain Score Using a 10-cm Visual Analog Scale (VAS) for Pain (0 = no Pain, 10 = Very Severe Pain).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, single-masked study with a parallel model and enrollment of 102. It lists the study as completed. The recorded start was 2012-11, and primary completion was 2013-05. The phase is listed as NA. The sponsor is Merz North America, Inc.

The arm descriptions add an important feature of the treatment comparison: the same participants received both devices at the same time, with one treatment on the left side of the face and the other on the right. The primary analysis description also refers to paired scores from the treatment and control folds. Thus, the record's design labels and its description of how the two devices were applied should be read together. The record does not explain how randomization assigned treatments to facial sides or give further detail about masking.

The primary outcome results report 101 participants for each condition. Because the arm descriptions indicate that the same participants received both treatments, these are not necessarily independent groups of people. The study is better understood as comparing paired facial-side measurements, although the registry also labels its model as parallel. Details about participant flow, reasons for any difference between enrollment and the reported outcome count, and the analysis population are not reported in the registry record.

The stated aim was to assess pain during nasolabial fold treatment using Radiesse® with lidocaine. The primary outcome was pain immediately after injection. Additional outcomes include pain scores at later time points and a clinically meaningful reduction in pain defined by a threshold on the visual analogue scale. The registry record does not report a sample-size justification or enough information to reconstruct the full conduct of the study.

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

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 Pain Score Using a 10-cm Visual Analog Scale (VAS) for Pain (0 = no Pain, 10 = Very Severe Pain), measured over Immediately after injection (Time 0).

The primary endpoint is the mean pain score immediately after injection, identified as Time 0. Pain was recorded on a 10-cm visual analogue scale, with 0 representing no pain and 10 representing very severe pain. The endpoint compares the score for the fold treated with Radiesse® mixed with lidocaine against the score for the fold treated with Radiesse® without lidocaine.

A visual analogue scale turns a participant's experience into a continuous numerical measure. A mean describes the average score across the participants included in the analysis; the standard deviation describes how spread out individual scores are around that average. The scale gives the analysis a direct, ordered way to compare reported pain between the two facial sides. As with any subjective rating, the score reflects participants' reported experience rather than an objective measurement of tissue or device performance.

The protocol description says that the primary assessment was selected a priori for analysis with a paired t-test, testing the null hypothesis that the mean of the within-participant differences was zero. Pairing is relevant because each participant contributes a score under each condition. The comparison can therefore focus on the difference between that participant's two scores rather than treating the scores as if they came from unrelated people.

The primary endpoint addresses pain immediately after injection. It does not by itself describe later pain, the experience of every participant, or outcomes beyond the measured scale. The reported means and comparison should be interpreted in that specific time point and measurement context.

7. Results Posted in the Registry

• Radiesse® Without Lidocaine: mean 6.73 versus 2.32 on control; difference 4.41 (95% CI 3.88 to 4.94), standardized effect d = 2.29; 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.

Visual Analogue Scale (VAS) Pain Score 15 Minutes Post Injection

• 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:
  • Radiesse® Without Lidocaine: mean 3.45 versus 1.06 on control; difference 2.39 (95% CI 1.88 to 2.90), standardized effect d = 1.29; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Radiesse® Without Lidocaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Visual Analogue Scale (VAS) Pain Score 30 Minutes Post Injection

• 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:
  • Radiesse® Without Lidocaine: mean 2.52 versus 0.73 on control; difference 1.79 (95% CI 1.29 to 2.29), standardized effect d = 0.99; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Radiesse® Without Lidocaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Visual Analogue Scale (VAS) Pain Score 45 Minutes Post Injection

• 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:
  • Radiesse® Without Lidocaine: mean 1.78 versus 0.48 on control; difference 1.30 (95% CI 0.88 to 1.72), standardized effect d = 0.86; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Radiesse® Without Lidocaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary pain measures at several post-injection time points, as well as a measure of participants meeting a clinically meaningful reduction threshold. The detailed posted numerical results include pain scores at 15 minutes, 30 minutes, and 45 minutes after injection. Across those reported measures, the mean scores are lower for the condition mixed with lidocaine, and the recalculated mean differences favor that condition in the same direction as the primary comparison. The registry reports two-sided test p-values of < 0.001 for these time-point analyses.

This overall pattern is consistent with the primary result: the between-condition difference is not limited to the immediate measurement among the time points with detailed results. It should not be generalized to every listed secondary outcome, because numerical results for the other listed outcomes are not reported in the registry record. In particular, the record does not provide detailed numerical results for the clinically meaningful reduction measure or for the later listed follow-up measurements.

Secondary outcomes are generally less definitive than a prespecified primary outcome when a study evaluates many outcomes or time points. Each additional test creates another opportunity to observe a small p-value by chance, even when the underlying null hypotheses are true. Statistical procedures can account for this multiplicity, but whether such procedures were used is not reported in the registry record. The secondary p-values should therefore be read as unadjusted evidence for their individual comparisons, not as a complete multiplicity-controlled body of evidence.

The registry lists 9 secondary outcomes, while detailed numeric results are posted for only some of them. The number and completeness of reported results matter when interpreting a pattern across outcomes. Without a reported analysis plan covering all secondary outcomes, it is not possible to assess whether the observed results reflect a prespecified testing strategy or how unreported results would affect an overall interpretation.

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

• Number of Participants With a Clinically Meaningful Reduction in Pain As Defined by a ≥ 2.0-cm Reduction in VAS
• Visual Analogue Scale (VAS) Pain Score 15 Minutes Post Injection
• Visual Analogue Scale (VAS) Pain Score 30 Minutes Post Injection
• Visual Analogue Scale (VAS) Pain Score 45 Minutes Post Injection
• Visual Analogue Scale (VAS) Pain Score 60 Minutes Post Injection
• Visual Analogue Scale (VAS) Pain Score 1 Week Post Injection
• Visual Analogue Scale (VAS) Pain Score 2 Weeks Post Injection
• Visual Analogue Scale (VAS) Pain Score 4 Weeks Post Injection

9. Statistical Interpretation

10. Statistical Methods Explained

What does a paired comparison mean?

In a paired analysis, each participant contributes measurements under both conditions, and the analysis focuses on the within-participant difference. Here, the arm descriptions say that both devices were used on opposite sides of the same participant's face at the same time. The protocol description says that the primary comparison was planned with a paired t-test. Pairing can be useful because characteristics shared by a participant, such as a general tendency to report higher or lower pain, may affect both measurements. Comparing the two sides within that participant can account for some of that shared variation.

The paired t-test evaluates whether the average within-participant difference is compatible with a null mean difference of zero. Its calculation depends on the variability of those paired differences, not solely on the separate standard deviations for each treatment condition. The registry gives the planned paired-test description and the sponsor's test result, but does not report the individual paired differences or their standard deviation. The recalculated comparison is an unadjusted calculation from the posted summary statistics, so it is not a reconstruction of participant-level paired data.

What does a mean difference describe?

A mean difference expresses the distance between two group or condition averages in the original measurement units. The primary scale uses units on a 10-cm scale. The recalculated estimate is expressed as the score without lidocaine minus the score with lidocaine, so a positive estimate corresponds to a higher mean score in the condition without lidocaine. The sponsor reports the net difference using the reverse direction, which explains why its estimate carries a negative sign. Sign direction is a matter of subtraction order; the scale means and analysis labels are needed to interpret it.

A mean difference is not the same as an individual response. The reported average does not establish that each participant's score changed by that amount, or even that every participant had a difference in the same direction. Individual response distributions are not reported in the registry record.

How should the p-value be read?

A p-value describes how incompatible the observed data are with a specified null hypothesis under the statistical model. In the primary analysis, the null hypothesis is that the mean paired difference is zero. A small p-value indicates that data at least as incompatible with that null would be unusual if the null and model assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of the observed difference.

The recalculated unadjusted p-value is <0.001; the registry's own two-sided test reports p < 0.001. These are reported as written and should not be treated as exact values. Both indicate strong statistical evidence against a zero mean difference under their respective analyses. The registry record does not describe adjustment for multiple comparisons.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the observed estimate under a specified statistical procedure and its assumptions. It helps readers assess precision as well as direction. The primary recalculated interval is 3.88 to 4.94 for the difference expressed as without lidocaine minus mixed with lidocaine. Its endpoints are both positive, and the interval does not include zero. The interval does not mean that there is a 95% probability that the true value lies within this particular range. In repeated use of the same method under its assumptions, intervals constructed in this way would cover the fixed target value at the stated confidence level at the stated frequency.

The registry's own primary analysis does not include a confidence interval. The recalculated interval uses posted summary statistics and is not a replacement for an analysis based on individual paired observations. Its interpretation should therefore remain tied to the recalculation method and the available data.

Why does over-dispersion matter?

Over-dispersion is a general concern when observed variation is greater than a statistical model assumes. If a model understates variability, uncertainty can appear smaller than it is, which can make confidence intervals too narrow and p-values too small. If variation is modeled appropriately, inferential results better reflect the spread in the data. The primary endpoint is continuous and reported as a mean with a standard deviation, and the registry describes a paired t-test. The record does not report a check of the paired differences' distribution, a model assessment, or an alternative analysis for departures from the test assumptions. It is not possible to determine from the registry record whether over-dispersion or other distributional concerns were assessed.

What is the role of recalculation?

Recalculated statistics offer a transparent, simple comparison based on the posted summary values. They can help readers understand an estimate and its uncertainty, but they need not reproduce the sponsor's analysis when the underlying design is paired or when different assumptions or calculation methods are used. In this study, the protocol describes paired testing, while recalculation from summary statistics does not use the participant-level paired differences. The registry's reported analysis is therefore essential context, and any disagreement would make the sponsor's own analysis take precedence. The posted discrepancy flag is false.

11. Confidence Intervals and Precision

The primary recalculated mean difference is 4.41 units on the scale, expressed as the mean score without lidocaine minus the mean score with lidocaine. Its 95% confidence interval runs from 3.88 to 4.94. The interval gives a range for the mean difference that is compatible with the recalculation and its assumptions. Because the entire interval is above zero, the estimated direction is not dependent on the point estimate alone.

The interval also shows that the estimate is not known with perfect precision. Its lower and upper limits differ, reflecting sampling uncertainty. A confidence interval is not a guarantee that the true effect lies within its limits, nor does it describe the range of individual participants' scores or differences. Those individual-level distributions are not reported in the registry record.

The sponsor's analysis reports a mean difference of -4.41 but no confidence interval. Its sign uses the reverse comparison direction; the p-value is reported as < 0.001. The recalculated interval is based on posted summary statistics, whereas the protocol describes a paired t-test. Since the paired participant-level values are not reported, the interval cannot be independently verified as a paired-data interval from the registry record. The registry reports no discrepancy between the sponsor result and the recalculation.

Precision should be considered alongside the outcome's scope: the estimate concerns average pain immediately after injection on the specified visual analogue scale. It does not quantify uncertainty for the later time points or other outcomes.

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 effects, not the trial's original design calculations. They give participants per arm for 80% power and participants per arm for 90% power. They are not total event counts because the primary outcome is continuous, not a time-to-event outcome.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect: 100%, 75%, or 50%. The figures answer a hypothetical design question: under those assumptions, how many participants per arm would be needed to detect an effect of the specified size at the selected power level?

Power is the probability that a study would reject the null hypothesis under a particular assumed effect and statistical model. The 80% and 90% columns represent different target probabilities of detecting that assumed effect if it were present. A higher target power generally calls for a larger planned sample under otherwise similar assumptions. Smaller effects need more participants because they are harder to distinguish from the variation in the outcome.

These values are not observed power. They do not describe the probability that the completed study's result is correct, and they do not establish what the original investigators planned. The registry record does not report the study's original sample-size justification or design assumptions. The planning values are illustrative only and should not be interpreted as evidence that the completed trial was designed around the observed result.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 4.410; pooled standard deviation σ = 1.923.
2. n = 2 × (1.96 + 0.842)² × 1.923² / 4.410² = 3.0, rounded up to 3 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
delta <- 4.41                      # observed difference in means
sigma <- 1.9226674179379                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1069354)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 75% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 50% of observed effect: n per arm = 12 (80% power), 16 (90% power)
power.t.test: 4.2 
Simulated power at n = 3 per arm: 0.562 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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's own primary analysis is a two-sided t-test. It reports a net mean difference of -4.41 and p < 0.001. The negative sign reflects a subtraction direction opposite to the recalculated estimate, which is expressed as the score without lidocaine minus the score with lidocaine. The reported group means, 2.32 with lidocaine and 6.73 without lidocaine, clarify the direction of the result.

The recalculation from posted summary statistics gives a mean difference of 4.41, a 95% confidence interval from 3.88 to 4.94, and an unadjusted p-value of <0.001. The sponsor result and recalculation are directionally consistent once the difference conventions are aligned. The sponsor's own analysis does not report a confidence interval in the registry record.

The protocol description states that the primary outcome was selected a priori for a paired t-test, reflecting the fact that the same participants received both conditions on opposite facial sides. A recalculation from summary statistics does not have access to the paired differences, so it may not reproduce every detail of that planned analysis. The registry record marks the discrepancy flag as false. If a discrepancy were present, the sponsor's own analysis would take precedence; no such discrepancy is indicated in this record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers several outcomes, time points, or comparisons. Even if each individual test uses a valid procedure, looking across many tests increases the chance that at least one result will appear statistically notable by chance. A prespecified primary outcome helps focus the main confirmatory question. Here, the registry identifies immediate post-injection pain as the primary endpoint and lists secondary pain measurements at later time points, together with a clinically meaningful reduction measure.

The registry record does not report whether the secondary analyses were adjusted for multiplicity, whether a hierarchy among secondary outcomes was prespecified, or whether any other method was used to control the overall error rate. The reported secondary p-values should therefore be interpreted as individual, unadjusted comparisons. A consistent pattern can be informative, but it does not remove the need to consider the number of analyses or the possibility of selective reporting.

Missing-data handling is also not reported in the registry record. The record gives enrollment of 102 and primary outcome counts of 101 in each condition, but does not explain why the reported outcome counts differ from enrollment, how missing measurements were treated, or whether all eligible participants were included in the primary analysis. It also does not report whether participants with incomplete paired measurements were excluded or handled in another way.

The analysis population is not specified beyond the reported outcome counts. The registry record does not say whether the analysis followed an intention-to-treat principle, a per-protocol approach, or another definition. It also does not describe sensitivity analyses for missing data. These omissions limit assessment of how robust the results are to exclusions or incomplete observations.

These details matter because analyses across outcomes and choices about incomplete data can influence estimates and uncertainty. The reported primary result remains the posted result, but the absent information constrains how fully its prespecification, multiplicity control, and population coverage can be evaluated.

16. 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 2% reporting threshold.

Most frequent non-serious adverse event terms

For serious adverse events, the registry reports 0 affected participants among 101 at risk in the Radiesse® mixed with lidocaine group and 0 affected participants among 101 at risk in the Radiesse® without lidocaine group. These are participant counts for the categories recorded as serious adverse events; they do not establish that no other adverse events occurred.

The registry separately reports other adverse events affecting 90 participants among 101 at risk with lidocaine and 92 participants among 101 at risk without lidocaine. The record does not provide serious-event terms because no serious events are listed. Death counts are not reported in the registry record.

Zero recorded serious adverse events in these groups is a description of the posted safety data, not proof that serious events are impossible or that the conditions have equivalent safety. The registry record does not provide event-level details, severity breakdowns for other events, or additional context needed to assess the nature of those events.

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

The posted data show that the mean immediate pain score was lower for the facial side treated with Radiesse® mixed with lidocaine than for the side treated without lidocaine. The primary means were 2.32 and 6.73, respectively, on a scale where 0 is no pain and 10 is very severe pain. The recalculated mean difference, stated as without lidocaine minus mixed with lidocaine, is 4.41 units, with a 95% confidence interval from 3.88 to 4.94. The sponsor's own analysis reports p < 0.001, and the recalculated unadjusted p-value is <0.001.

That result concerns an average score immediately after injection among participants contributing to the reported analysis. It does not mean that every participant experienced the same difference, that each participant had less pain on the lidocaine side, or that the mean difference describes the entire distribution of experiences. Individual paired results are not reported in the registry record.

The outcome is a participant-reported pain scale. It captures pain as recorded on that scale and at that time; it does not establish effects on other outcomes or settings. The registry lists later pain assessments and a clinically meaningful reduction measure, but detailed numerical results for all listed secondary outcomes are not reported in the registry record. The available primary result cannot fill in those missing results.

The study's participant-level application of both conditions to opposite facial sides supports a within-participant comparison, as described in the protocol. However, details of randomization, masking, missing data, and the analysis population are not reported. The record also does not report a sample-size justification or adjustment for multiple secondary tests. These gaps limit how broadly the result can be generalized and how fully its statistical assumptions can be evaluated.

The findings describe the recorded comparison and its uncertainty. They do not constitute medical advice or a recommendation about treatment. They do not establish outcomes beyond the measured pain scores or resolve questions not addressed in the registry record.

18. Why This Trial Matters Statistically

This study illustrates why understanding the unit of comparison matters. The arm descriptions state that the same participants received both devices on opposite facial sides at the same time, and the protocol describes a paired t-test for the primary endpoint. That structure differs from a comparison in which each condition is assigned to a separate set of participants. A paired analysis uses within-participant differences, while a simple calculation from separate means and standard deviations may not capture the correlation between a participant's two scores.

It also illustrates the value of checking the direction of a reported mean difference. The sponsor's result is -4.41, while the recalculated comparison is +4.41 because the subtraction order is reversed. The group means resolve the apparent sign conflict. Without stating the direction explicitly, a reader could misunderstand which condition had the higher average score.

Confidence intervals add information beyond a p-value. The recalculated interval gives a range for the average difference under the calculation assumptions, while the sponsor's record reports a p-value but no interval. Considering both statistical evidence and precision helps avoid treating a thresholded significance result as a complete account of the data.

Finally, the registry lists multiple secondary outcomes, but detailed numerical results are not available for all of them, and multiplicity handling is not reported. This makes it important to distinguish the primary analysis from exploratory or unadjusted secondary comparisons. Together, these issues show how design, analysis, reporting completeness, and uncertainty all shape what can be learned from a clinical trial result.

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.

The registry record does not provide the detailed participant characteristics needed to judge how closely the analyzed participants represent other groups undergoing nasolabial fold treatment. The primary outcome reports 101 participants per condition, while enrollment is 102; reasons for the difference and the handling of incomplete observations are not reported.

The record labels the study randomized, single-masked, and parallel, while the arm descriptions state that the same participants received both devices simultaneously on opposite sides of the face. The primary analysis description is paired. The registry does not explain the relationship among these design labels, the randomization process, or the masking procedures. This makes it difficult to independently assess whether the reported design and analysis fully reflect the treatment assignment and data structure.

Individual paired scores, the distribution of paired differences, and the standard deviation of those differences are not reported. Consequently, the recalculated summary-statistic comparison cannot reproduce a participant-level paired analysis. The sponsor's primary analysis provides a test result but no confidence interval in the registry record.

Detailed numerical results are posted for only some of the secondary outcomes listed in the record. Results for the other listed secondary measures are not reported in the registry record. Multiplicity procedures, missing-data methods, the analysis population, sensitivity analyses, and the original sample-size justification are also not reported.

The safety record reports no serious adverse events in either condition, but does not provide event-level information for the other adverse events. These limitations do not change the posted primary values, but they constrain independent assessment of generalizability, precision under the intended paired analysis, and the completeness of the outcome picture.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluation of Pain With Radiesse® With Lidocaine for Nasolabial Folds — NCT01069354.
• Registry record last updated 2018-05-30; status last verified 2017-09.
• Results first posted 2018-05-30.
• 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

The completed randomized study evaluated pain during nasolabial fold treatment with Radiesse® Injectable Dermal Filler mixed with lidocaine compared with the same filler without lidocaine. The registry describes single masking and a parallel model; the arm descriptions say that participants received both devices at the same time on opposite sides of the face.

The primary endpoint was pain immediately after injection on a 10-cm visual analogue scale. Mean scores were 2.32 with lidocaine and 6.73 without lidocaine. The sponsor reports a net mean difference of -4.41 and p < 0.001 from a two-sided t-test. The recalculated difference, expressed as without lidocaine minus mixed with lidocaine, is 4.41, with a 95% confidence interval from 3.88 to 4.94 and an unadjusted p-value of <0.001.

The record lists multiple secondary outcomes but does not report detailed results for all of them. It records 0 serious adverse events among 101 participants at risk in each condition. Important details about missing data, analysis populations, multiplicity, and the original sample-size justification are not reported in the registry record.