A Study To Assess the Safety and Effects of OnabotulinumtoxinA (BOTOX) Intramuscular Injection in Adult Participants With Moderate to Severe Platysma Prominence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Assess the Safety and Effects of OnabotulinumtoxinA (BOTOX) Intramuscular Injection in Adult Participants With Moderate to Severe Platysma Prominence (NCT04949399), a randomized phase 3 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The primary endpoint is a safety measure, not a direct measure of improvement in platysma prominence. The registry’s secondary measures address participants’ and investigators’ assessments at specific time points. Those outcomes can inform the clinical question from different perspectives, but they do not replace the primary safety comparison or establish a complete account of benefit and harm. The record identifies the study as completed and lists 18 outcome measures, with 15 analyses posted.

3. Trial Design

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The registry also describes masking as triple. Randomization means that assignment to treatment groups was determined by an allocation process rather than by participant or investigator choice. A parallel-group design assigns each participant to one study arm. The record does not identify which specific people or roles were masked, so the meaning of triple masking cannot be further specified from the registry information.

The study enrolled 408 participants. The registry lists 209 participants in the placebo arm and 199 in the BOTOX arm for the primary adverse-event analysis. The BOTOX group received onabotulinumtoxinA injected into the platysma muscle on Day 1; the placebo group received placebo injected into the same muscle on Day 1. The registry summary describes a single treatment and a four-month study, with regular monthly visits.

The primary safety endpoint counted participants with adverse events from enrollment to Day 120. Its analysis population was the Safety Analysis Set, defined in the record as all participants who received at least one dose of study drug. The record lists the study as completed. It gives a start date of 2021-07-08 and a primary completion date of 2022-12-20.

Several details that would help interpret the design are not reported in the registry record. These include the planned sample-size justification, the original analysis plan, any interim analyses, the handling of missing outcome data, and the specific roles covered by masking. The enrollment figure is a recorded trial total, but it does not by itself explain how the target enrollment was chosen or whether the trial was designed around the primary safety endpoint or one of the secondary outcomes.

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: The ITT Population included all randomized participants (N=408); the modified ITT Population included all randomized participants with a baseline summary score ≥ 19 on the ANLFQ: Impacts questionnaire (N=367). The Safety Analysis Set included all participants who were treated with at least 1 dose of study drug (N=408).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set included all participants who received at least 1 dose of study drug.

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: Baseline analyses were performed on the ITT population, consisting of all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over Enrollment to Day 120.

The primary endpoint is the number of participants with adverse events from enrollment to Day 120. The registry defines an adverse event as an untoward medical occurrence in a participant administered a pharmaceutical product; the occurrence does not necessarily have to be caused by the treatment. The measure therefore counts participants with at least one recorded adverse event during the stated period, rather than counting every event experienced by each participant.

For this endpoint, the registry reports 45 participants with adverse events among 209 in the placebo group and 47 among 199 in the BOTOX group. The safety analysis included participants who received at least one dose. This endpoint is used to describe and compare observed safety events across the randomized groups during follow-up. It can show how many participants were recorded as having an event, but a participant count alone does not describe the event’s severity, duration, cause, or clinical importance.

The endpoint also does not measure treatment effectiveness. The registry’s secondary outcomes include participant and investigator assessments related to appearance, satisfaction, and bother. These are separate outcomes with their own definitions and time points. Interpreting the safety count alongside those outcomes requires attention to the different questions each measure addresses, the analysis populations, and the uncertainty around group comparisons.

The registry record does not report a treatment attribution requirement for the primary adverse-event count, and the event definition explicitly allows events without a causal relationship to treatment. Consequently, the count should be read as adverse events observed in the study population, not as a count of events proven to have been caused by the assigned injection.

7. Results Posted in the Registry

• BOTOX: 23.6% (47/199) versus 21.5% (45/209) on control; risk difference 2.1 percentage points (95% CI -6.0 to 10.2), risk ratio 1.10 (0.77–1.57); unadjusted two-proportion z-test p = 0.614.

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 Responses of "Satisfied" or "Very Satisfied" on the Appearance of Neck and Lower Face Questionnaire (ANLFQ): Satisfaction (Follow-up) Item 5 (Effect of Treatment) at Day 14

• 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:
  • BOTOX: 65.8% (131/199) versus 11.0% (23/209) on control; risk difference 54.8 percentage points (95% CI 47.0 to 62.7), risk ratio 5.98 (4.02–8.91); 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 BOTOX than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Responses of 'Not at All Bothered' or 'A Little Bothered' on the Bother Assessment Scale - Platysma Prominence (BAS-PP) Scale Item 2 (Jawline) at Day 14

• 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:
  • BOTOX: 53.8% (107/199) versus 14.8% (31/209) on control; risk difference 38.9 percentage points (95% CI 30.5 to 47.4), risk ratio 3.63 (2.56–5.14); 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 BOTOX than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Responses of 'Not at All Bothered' or 'A Little Bothered' on the BAS-PP Scale Item 1 (Vertical Neck Bands) at Day 14

• 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:
  • BOTOX: 52.3% (104/199) versus 7.2% (15/209) on control; risk difference 45.1 percentage points (95% CI 37.3 to 52.9), risk ratio 7.28 (4.39–12.07); 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 BOTOX than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted Day 14 secondary outcomes cover satisfaction with treatment effect and participant-reported bother related to the jawline and vertical neck bands. Across these outcomes, the recorded response percentages are higher in the BOTOX group than in the placebo group for the specified favorable response categories. The sponsor-reported Cochran-Mantel-Haenszel differences are positive, with confidence intervals above zero and p-values below .0001. This is a consistent direction across the three posted Day 14 comparisons, but each outcome represents a distinct experience or assessment.

These results complement the primary adverse-event count by addressing participant perceptions rather than the occurrence of any adverse event. They do not establish the same conclusion as the primary endpoint, which is a safety measure. Nor do they represent the entire set of registered secondary outcomes: the registry lists additional appearance assessments, time points, and questionnaire measures. The listed secondary results are therefore a partial view of the registered outcome program.

Secondary findings generally carry less evidential weight when the record does not state how multiple comparisons were handled. Testing many outcomes can increase the chance that some results appear statistically notable even when there is no underlying difference for those measures. Prespecified outcome hierarchies, multiplicity adjustments, or a clearly defined confirmatory strategy can help interpret that issue, but such details are not reported in the registry record. The unadjusted nature of a p-value should therefore remain visible in interpretation.

Statistical evidence in a secondary endpoint does not by itself establish clinical importance, durability, or generalizability. The assessments are tied to Day 14, and the registry record does not supply the full results for every listed measure or details of missing-data handling. The results can be described as the posted comparisons for the named outcomes and time point, while avoiding a claim that they settle the broader effectiveness question.

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

• Percentage of Participants Who Achieved Grade 1 or 2 (Minimal or Mild) According to Investigator's Assessment Using C-APPS at Maximum Contraction at Days 14, 30, 60, 90, and 120
• Percentage of Participants Who Achieved Grade 1 or 2 (Minimal or Mild) According to Participant's Assessment Using P-APPS at Maximum Contraction at Days 14, 30, 60, 90, and 120
• Percentage of Participants With Responses of "Satisfied" or "Very Satisfied" on the Appearance of Neck and Lower Face Questionnaire (ANLFQ): Satisfaction (Follow-up) Item 5 (Effect of Treatment) at Day 14
• Percentage of Participants With Responses of 'Not at All Bothered' or 'A Little Bothered' on the Bother Assessment Scale - Platysma Prominence (BAS-PP) Scale Item 2 (Jawline) at Day 14
• Percentage of Participants With Responses of 'Not at All Bothered' or 'A Little Bothered' on the BAS-PP Scale Item 1 (Vertical Neck Bands) at Day 14
• Change From Baseline on the Appearance of Neck and Lower Face Questionnaire (ANLFQ): Impacts Summary Score at Day 14
• Percentage of Participants Who Achieved at Least 1-Grade Improvement From Baseline Based on Investigator's Assessment Using C-APPS at Maximum Contraction at Days 14, 30, 60, 90, and 120
• Percentage of Participants Who Achieved at Least 1-Grade Improvement From Baseline Based on Participant's Assessment Using P-APPS at Maximum Contraction at Days 14, 30, 60, 90, and 120

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each person is counted as having had an adverse event or not during the specified follow-up. The registry reports the number with events and the number analyzed in each group. The unadjusted comparison is expressed as a risk difference. In general, a risk difference compares the proportion with the outcome in one group against the proportion in the other. A value of zero corresponds to equal observed proportions; values on either side indicate a difference in opposite directions.

The confidence interval around a risk difference describes a range of values reasonably compatible with the observed data under the statistical method used. It reflects sampling uncertainty, not uncertainty about every possible source of bias or error. For the primary endpoint, the interval includes zero. This means the posted data do not rule out no group difference at the confidence level represented by the interval. The unadjusted p-value of 0.614 is also not evidence that the groups are exactly equivalent. A non-small p-value can arise when the observed difference is modest relative to the uncertainty.

For secondary binary outcomes, the registry posts percentages, confidence intervals, and sponsor-reported Cochran-Mantel-Haenszel analyses. In general, the Cochran-Mantel-Haenszel method estimates a group association while accounting for strata. The registry record does not identify the stratification factors used, so it is not possible to describe what was adjusted for in these reported analyses. The sponsor-reported differences and confidence intervals should be distinguished from the posted unadjusted recalculations, which use summary statistics and do not reproduce an adjusted analysis.

The secondary comparisons are reported as differences in percentages, with confidence intervals and p-values. In general, a confidence interval gives an indication of both the direction and precision of an estimated contrast. A narrow interval indicates greater precision than a wide one, given the method and data. A p-value assesses how unusual data at least as incompatible with a specified null hypothesis would be under the model’s assumptions. It is not the probability that the null hypothesis is true, and it does not describe the size or importance of an effect.

What does an unadjusted comparison mean?

An unadjusted comparison uses the reported group summaries without accounting for additional covariates or strata. It can be useful for a transparent description of the observed groups, but it may differ from a trial’s prespecified model or a sponsor’s adjusted analysis. The primary comparison is identified as an unadjusted recalculation from posted summaries. The registry record lists no conflicting sponsor analysis for that endpoint, and the discrepancy flag is false. For the secondary outcomes with reported sponsor analyses, the Cochran-Mantel-Haenszel results are distinct from simple unadjusted calculations.

Why do binary outcomes use participant counts?

When an outcome records whether each participant had at least one event, the number of participants with that outcome is the numerator and the number analyzed is the denominator. This differs from an event-rate analysis, which would count repeated events or use time at risk. The primary endpoint is explicitly a participant count. It should not be interpreted as the number of all adverse-event occurrences, because a participant may experience more than one event and the posted primary measure counts participants with events.

Why can over-dispersion matter?

Over-dispersion is a general concern when data vary more than a statistical model assumes. It can make standard errors too small if the model does not allow for the extra variability, producing confidence intervals that are too narrow and p-values that appear more compelling than warranted. The primary measure is a binary participant outcome, not a count model with a reported dispersion parameter. The registry record does not report an over-dispersion assessment or a count-model analysis for this endpoint, so over-dispersion should not be inferred from the event counts.

What does the analysis population tell us?

The primary Safety Analysis Set includes all participants who received at least one dose of study drug. That definition means the primary endpoint is not described as an analysis of every randomized participant regardless of treatment receipt. The registry record does not report whether a separate intention-to-treat analysis was performed, how participants with incomplete follow-up were handled, or which populations were used for the secondary outcomes. Those omissions limit the ability to determine whether the posted analyses consistently preserve the original randomized comparison.

Statistical significance and clinical interpretation are separate. A small p-value can accompany a precisely estimated difference, but does not by itself establish importance; a larger p-value does not show equivalence. Interpretation should consider the estimate, its confidence interval, the outcome’s definition, the study population, and whether the analysis was planned. The registry record does not report the complete statistical analysis plan, so some details necessary to evaluate those choices are unavailable.

11. Confidence Intervals and Precision

The primary adverse-event comparison has an unadjusted confidence interval that extends from -0.060 to 0.102 for the risk difference. Because the interval crosses zero, the posted results are compatible with no difference and with differences in either direction. This is an important qualification to the point estimate and the observed group counts. The p-value of 0.614 is consistent with the interval not establishing a clear separation, but neither statistic proves that the groups are equivalent.

The precision of an estimate depends on the amount of information in the data and on the outcome’s variability. The primary comparison includes 209 participants in the placebo group and 199 in the BOTOX group. The observed event counts are 45 and 47, respectively. Those counts describe the available information for the endpoint, but they do not eliminate uncertainty about the underlying group rates. The interval is the most direct summary of that uncertainty in the posted comparison.

For the Day 14 secondary measures, the registry reports confidence intervals for each group’s percentage, and the sponsor analyses report intervals for the group differences. These intervals indicate uncertainty in the respective estimates. The sponsor-reported difference intervals are 46.8 to 62.8 for treatment-effect satisfaction, 30.5 to 47.8 for the jawline bother response, and 36.8 to 52.5 for the vertical-neck-band bother response. Each interval is specific to its outcome and analysis. These secondary estimates should not be treated as more precise merely because their p-values are small; precision is reflected in the interval’s width and depends on the measure and analysis.

Confidence intervals do not account for every limitation. They do not correct for unreported missing-data handling, possible selective reporting, or multiple testing. They also do not establish whether a difference is meaningful to participants. Precision is one part of interpretation, alongside the study design, outcome definitions, analysis population, and completeness of the registry record.

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 illustrations are planning calculations based on an observed effect, not a description of the trial’s original design justification. For outcomes other than time-to-event measures, the figures are participants per arm; time-to-event illustrations, if present, would give total events. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The detectable effect is set to the stated fraction of the observed effect.

The 80% power column describes the number of participants per arm the illustration estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect and model were correct. The 90% power column gives the corresponding planning quantity for a 90% chance. These are planning targets, not predictions about what a future study will find. The sample sizes are not observed power.

Rows that plan for 100% of the observed effect use the full observed contrast as the target. Rows planning for 75% or 50% use smaller target effects. Smaller effects generally require more participants to distinguish them from random variation under the same assumptions. The illustrations therefore show how sensitive required enrollment can be to the effect chosen for planning.

The registry record does not report the assumptions or calculation used to set the trial’s original enrollment target. These illustrations cannot establish that the completed study was adequately or inadequately powered for its primary safety endpoint, nor can they recover the original design rationale. They should be read as hypothetical planning examples derived from the observed effect, with the listed assumptions, rather than as evidence about the trial’s actual design process.

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 = 0.215; treatment proportion p₁ = 0.236; average p̄ = 0.226.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5912 = 1.1588.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5911 = 0.4974.
4. n = (1.1588 + 0.4974)² / (0.0209)² = 6,298.2, rounded up to 6,299 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 <- 0.215311004784689                          # control proportion
p1 <- 0.236180904522613                          # 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(4949399)
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 = 6,299 (80% power), 8,432 (90% power)
 75% of observed effect: n per arm = 11,106 (80% power), 14,867 (90% power)
 50% of observed effect: n per arm = 24,780 (80% power), 33,173 (90% power)
power.prop.test: 6298.2 
Simulated power at n = 6,299 per arm: 0.798 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists 18 outcome measures and 15 analyses, including the primary safety endpoint and a range of secondary outcomes. The secondary measures span participant and investigator assessments, satisfaction, bother, impacts, and several follow-up time points. When many outcomes are analyzed, the chance of obtaining at least one small p-value by chance can rise if each test is considered separately. This is the general multiplicity problem.

The registry record does not report a multiplicity adjustment, a testing hierarchy, or which outcomes were intended to be confirmatory versus exploratory. Consequently, the posted secondary p-values should be interpreted as individual, unadjusted evidence rather than as a family-wise controlled set of tests. This does not negate the reported findings; it limits how confidently they can be treated as confirmatory evidence across all outcomes.

Missing-data methods are also not reported in the registry record. The record does not explain how participants with missing assessments, withdrawals, or incomplete follow-up were handled for the primary endpoint or for the secondary outcomes. It also does not give the analysis population for the secondary endpoints in the information. If outcome availability differs between groups or relates to participants’ responses, the observed percentages may not fully represent everyone randomized. The registry information is insufficient to evaluate that possibility.

For the primary endpoint, the reported Safety Analysis Set includes participants who received at least one dose. The record does not describe an intention-to-treat analysis or provide details about participants who were randomized but did not receive treatment. This population definition is relevant because the primary comparison is based on treated participants rather than, as far as the record states, every randomized participant.

Interim analyses, stopping rules, and the full statistical analysis plan are not reported in the registry record. Without those details, readers cannot verify the planned timing and hierarchy of analyses, the prespecification of model choices, or the handling of all registered outcomes. These are gaps in reporting, not evidence that a particular procedure was or was not used.

15. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.5%), cellulitis (0.5%), ophthalmic vascular thrombosis (0.5%), thyroid cancer (0.5%), subarachnoid haemorrhage (0.5%).

The registry reports serious adverse events in 3 of 209 participants in the placebo group and 2 of 199 participants in the BOTOX group. It reports zero deaths in both groups. These figures count participants with serious adverse events, rather than providing a rate over person-time or a full account of each event’s timing and course. The record also lists 11 participants with other adverse events in each group in the separate adverse-event summary.

The listed serious-event terms include appendicitis, cellulitis, ophthalmic vascular thrombosis, thyroid cancer, and subarachnoid haemorrhage, each recorded at 0.5%. The registry information does not attribute each listed term to a treatment arm, nor does it give enough detail to determine whether events were judged related to study treatment. The overall adverse-event definition does not require a causal relationship.

These counts are descriptive. With few serious events, the observed counts alone provide limited precision for comparing groups, and they do not establish a difference or equivalence in serious-event risk. Interpretation also depends on follow-up, event definitions, attribution procedures, and completeness of reporting, some of which are not detailed in the registry record.

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

The primary result describes adverse events recorded during follow-up among participants who received at least one dose. The counts were 45 in the placebo group and 47 in the BOTOX group, with an unadjusted comparison whose confidence interval includes zero. The result does not establish a clear group difference in the proportion of participants with an adverse event. It also does not demonstrate that the groups have identical safety profiles.

The endpoint counts participants with adverse events whether or not the events were caused by treatment. It is therefore not a tally of treatment-related events, nor a measure of severity or burden. Serious adverse events and deaths are reported separately, with few serious events and no deaths recorded in either group. These descriptive data do not provide enough detail to assess every possible type, timing, or consequence of an adverse event.

The secondary Day 14 outcomes show differences in recorded satisfaction and bother responses between the groups. They measure participant-reported responses for particular questions, not every aspect of appearance or experience. The registry lists other outcomes and time points, but the record does not include full results for all of them in the information available for this analysis. The reported secondary findings should therefore be interpreted as specific to their defined measures and analyses.

Statistical evidence does not settle whether an observed difference is important to participants, persists beyond the measured time point, or applies to people outside the studied population. The registry record does not report a minimum clinically important difference, the complete analysis plan, or all missing-data methods. It also does not provide a basis to infer comparative results for outcomes that are not posted.

In short, the posted results describe event counts and selected Day 14 response comparisons in this completed study. They do not establish a comprehensive benefit-harm conclusion, prove causation for adverse events, or resolve uncertainty left by missing methodological details. Those limits are especially relevant when reading secondary outcomes without a documented multiplicity strategy.

17. Why This Trial Matters Statistically

This trial illustrates why a primary endpoint’s definition matters as much as its numerical result. The primary outcome counts participants with at least one adverse event, which is different from counting all events, identifying treatment-related events, or measuring event severity. A reader who treats these as interchangeable would draw more from the endpoint than it can support.

It also demonstrates the distinction between a point estimate and its precision. The primary comparison’s confidence interval crosses zero, while the unadjusted p-value is 0.614. The two summaries together show that the observed counts do not establish a clear difference, but do not prove equivalence. Reporting the interval alongside the p-value makes the range of compatible differences more visible.

The secondary findings provide a useful contrast in statistical interpretation. Several Day 14 response comparisons have sponsor-reported intervals above zero and p-values below .0001, yet the record does not describe multiplicity control or a prespecified hierarchy. A small p-value can be notable for an individual comparison while still requiring caution when multiple outcomes are tested. This is a general issue in clinical trials, not a reason to disregard the posted observations.

Finally, the record shows how reporting gaps shape interpretation. The primary safety analysis population is described, but secondary analysis populations and missing-data methods are not. The original sample-size justification and statistical analysis plan are also not reported in the registry record. Statistical reading therefore involves both evaluating the estimates that are posted and recognizing which design and analysis details remain unavailable.

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 record gives the primary safety counts and a comparison, but the primary endpoint is broad: an adverse event need not be causally related to the assigned treatment. The count does not provide event-level severity, duration, recurrence, or attribution. The separate serious-event summary offers limited counts and a short list of terms, but does not provide a full account of clinical context.

Although the study is described as triple masked, the registry does not identify the roles masked. The exact randomization procedures and any stratification factors are not reported in the record. The sponsor-reported Cochran-Mantel-Haenszel analyses for secondary outcomes are named, but the strata used are not identified. These omissions make it difficult to assess the details of allocation and adjusted analysis.

The registry record does not report how missing observations were handled, the analysis populations for the secondary outcomes, or whether all registered outcomes were analyzed as planned. It lists more outcome measures than posted analyses. The available secondary results cover selected Day 14 outcomes and do not provide the full set of results at all registered time points. The absence of a reported result should not be interpreted as a null finding.

No multiplicity strategy, interim analysis information, full statistical analysis plan, or original sample-size justification is reported in the registry record. The sample-size illustrations are based on observed effects and stated planning assumptions; they cannot establish the rationale for the completed trial’s enrollment. These reporting limitations constrain assessment of prespecification, missingness, and the strength of confirmatory claims.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study To Assess the Safety and Effects of OnabotulinumtoxinA (BOTOX) Intramuscular Injection in Adult Participants With Moderate to Severe Platysma Prominence — NCT04949399.
• Registry record last updated 2024-11-20; status last verified 2024-10.
• Results first posted 2024-11-20.
• 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

The registry identifies NCT04949399 as a completed Phase 3, randomized, triple-masked, parallel-group, placebo-controlled study sponsored by AbbVie. It enrolled 408 adults with moderate to severe platysma prominence and compared a single Day 1 intramuscular injection of onabotulinumtoxinA with placebo. The study summary describes follow-up through Day 120.

The primary endpoint counted participants with adverse events from enrollment to Day 120 in the Safety Analysis Set. The registry reports 45 of 209 participants in the placebo group and 47 of 199 in the BOTOX group. The unadjusted comparison has a confidence interval that includes zero and an unadjusted p-value of 0.614. Serious adverse events were reported for 3 placebo participants and 2 BOTOX participants, with zero deaths in both groups.

Selected Day 14 secondary comparisons show higher recorded favorable response percentages in the BOTOX group. Interpretation is limited by unreported multiplicity procedures, missing-data handling, secondary analysis populations, and the original sample-size justification. The registry record supports description of the posted results, not a complete assessment of all registered outcomes or a comprehensive benefit-harm conclusion.