This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines and Frown Lines (NCT01189760), a randomized phase 3 study. The primary outcome is Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01189760 |
| Phase | Phase 3 |
| Condition | Facial Rhytides, Crow's Feet Lines, Glabellar Lines |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 917 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
The intent-to-treat population included all randomized participants. The registry reports 917 participants enrolled in a trial addressing facial rhytides, crow’s feet lines, and glabellar lines. For the primary endpoint, participants with missing values were counted as non-responders.
Intervention
One group received onabotulinumtoxinA 44 U total per treatment, injected into bilateral crow’s feet line and frown line areas. A second group received 24 U total onabotulinumtoxinA with placebo injections in those areas. Participants received two treatments 4 months apart.
Comparator
The comparator was normal saline injected into bilateral crow’s feet line and frown line areas per treatment. Participants in this group also received two treatments 4 months apart.
Primary question
At Day 30, what percentage of participants met the composite responder definition for crow’s feet line severity at maximum smile? A responder had to improve by at least 2 grades from baseline on the composite assessment, which used both Investigator and Subject Facial Wrinkle Scale assessments. The comparison was between each onabotulinumtoxinA regimen and normal saline.
3. Trial Design
This was a phase 3 randomized, double-masked, parallel-group trial sponsored by Allergan. The registry lists a total enrollment of 917 participants and a completed status. The recorded study start was 2010-09-01, and primary completion was 2011-03-01. The registry describes the study as evaluating safety and efficacy of botulinum toxin Type A compared with placebo for crow’s feet lines and frown lines.
Three groups were described: onabotulinumtoxinA 44 U, onabotulinumtoxinA 24 U with placebo, and placebo consisting of normal saline. In each group, injections were given into bilateral crow’s feet line and frown line areas. The treatment descriptions specify two treatments 4 months apart. The 44 U description identifies that amount as the total dose per treatment. The 24 U description identifies a total of 24 units and placebo injections per treatment.
Randomization means assignment to treatment groups was by chance; double masking means the record identifies the trial as double-masked, but the registry record does not specify which individuals were masked or how masking was maintained. A parallel design assigns participants to a group rather than describing a crossover between treatments.
The registry record does not report the randomization procedure, allocation concealment details, eligibility criteria, treatment adherence, or the intended sample-size justification. It also does not report interim analyses or the full statistical analysis plan. Those details should not be inferred from the trial’s design labels or enrollment figure.
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
| Stage | onabotulinumtoxinA 44U | onabotulinumtoxinA 24U | Placebo (Normal Saline) |
|---|---|---|---|
| STARTED | 305 | 306 | 306 |
| COMPLETED | 291 | 283 | 255 |
| NOT COMPLETED | 14 | 23 | 51 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population included all randomized participants. Participants with missing values are considered non-responders.
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.
| Characteristic | Unit | onabotulinumtoxinA 44U | onabotulinumtoxinA 24U | Placebo (Normal Saline) | Total |
|---|---|---|---|---|---|
| Participants analysed | 305 | 306 | 306 | 917 | |
| Age, Customized: <45 Years | Participants | 87 | 89 | 100 | 276 |
| Age, Customized: 45 to 65 Years | Participants | 204 | 200 | 194 | 598 |
| Age, Customized: >65 Years | Participants | 14 | 17 | 12 | 43 |
| Sex: Female, Male: Female | Participants | 267 | 273 | 263 | 803 |
| Sex: Female, Male: Male | Participants | 38 | 33 | 43 | 114 |
| CFL Severity as Assessed by the Investigator: Moderate | Participants | 109 | 115 | 113 | 337 |
| CFL Severity as Assessed by the Investigator: Severe | Participants | 196 | 191 | 193 | 580 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile, measured over Baseline, Day 30.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants who responded on a composite assessment of crow’s feet line severity at maximum smile, measured at Day 30. The composite used both the Investigator and Subject Facial Wrinkle Scales. Each scale used four grades: 0 for none, 1 for mild, 2 for moderate, and 3 for severe. A responder was defined as having at least a 2-grade improvement from baseline.
This is a binary endpoint: each participant is classified as a responder or non-responder, and the reported group result is the percentage who responded. The registry states that the intent-to-treat population included all randomized participants and that missing primary values were considered non-responses. That rule retains participants with missing endpoint values in the stated analysis population while assigning them to the non-responder category for this outcome.
A composite endpoint brings together the Investigator and Subject assessments under the stated responder definition. It therefore represents the trial’s specified combination of those assessments, rather than an outcome based solely on either the investigator’s rating or the participant’s rating. The endpoint is useful for comparing the proportion meeting a defined degree of improvement across randomized groups. It does not, by itself, describe every participant’s change, the distribution of grades, or outcomes beyond the stated assessment and time point.
7. Results Posted in the Registry
- onabotulinumtoxinA 44U: 21.3% (65/305) versus 0.0% (0/306) on control; risk difference 21.3 percentage points (95% CI 16.7 to 25.9); unadjusted two-proportion z-test p = <0.001.
- onabotulinumtoxinA 24U: 20.6% (63/306) versus 0.0% (0/306) on control; risk difference 20.6 percentage points (95% CI 16.1 to 25.1); unadjusted two-proportion z-test p = <0.001.
Risk difference: onabotulinumtoxinA 44U
95% CI: 16.7 to 25.9 percentage points
Recalculated from the posted summary statistics
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.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines | Binary Endpoint | Risk difference | +55.7 pts (49.9 to 61.6) | 10 per arm |
| Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile | Binary Endpoint | Risk difference | +77.7 pts (72.8 to 82.7) | 6 per arm |
| Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest | Binary Endpoint | Risk difference | +61.7 pts (55.4 to 67.9) | 9 per arm |
Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines
- 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:
- onabotulinumtoxinA 44U: 59.0% (180/305) versus 3.3% (10/306) on control; risk difference 55.7 percentage points (95% CI 49.9 to 61.6), risk ratio 18.06 (9.75–33.46); unadjusted two-proportion z-test p = <0.001.
- onabotulinumtoxinA 24U: 54.9% (168/306) versus 3.3% (10/306) on control; risk difference 51.6 percentage points (95% CI 45.7 to 57.6), risk ratio 16.80 (9.06–31.17); 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 onabotulinumtoxinA 44U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
- The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for onabotulinumtoxinA 24U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile
- 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:
- onabotulinumtoxinA 44U: 87.9% (268/305) versus 10.1% (31/306) on control; risk difference 77.7 percentage points (95% CI 72.8 to 82.7), risk ratio 8.67 (6.20–12.14); unadjusted two-proportion z-test p = <0.001.
- onabotulinumtoxinA 24U: 78.1% (239/306) versus 10.1% (31/306) on control; risk difference 68.0 percentage points (95% CI 62.2 to 73.7), risk ratio 7.71 (5.49–10.82); 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 onabotulinumtoxinA 44U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
- The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for onabotulinumtoxinA 24U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest
- 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:
- onabotulinumtoxinA 44U: 75.1% (220/293) versus 13.4% (40/298) on control; risk difference 61.7 percentage points (95% CI 55.4 to 67.9), risk ratio 5.59 (4.16–7.52); unadjusted two-proportion z-test p = <0.001.
- onabotulinumtoxinA 24U: 61.3% (182/297) versus 13.4% (40/298) on control; risk difference 47.9 percentage points (95% CI 41.1 to 54.6), risk ratio 4.57 (3.37–6.18); 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 onabotulinumtoxinA 44U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
- The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for onabotulinumtoxinA 24U than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
The secondary outcomes extend the primary question by examining other ways of describing crow’s feet line severity and change. The posted numerical results include investigator-rated none-or-mild severity at maximum smile, at least a 1-grade improvement at maximum smile, and at least a 1-grade improvement at rest. Across these outcomes, the observed proportions are higher in the onabotulinumtoxinA groups than in the saline group, and the posted comparisons report unadjusted p < 0.001.
This direction is broadly consistent with the primary result, which used a stricter composite responder definition requiring at least a 2-grade improvement at maximum smile. The outcomes are not interchangeable: they use different thresholds, assessment sources, or conditions such as smiling versus resting. Their agreement in direction is supportive as a descriptive pattern, but it does not make them repetitions of the primary endpoint or establish that every listed secondary measure has the same evidential strength.
The registry’s secondary outcome list also includes subject global assessment, self-perception of age, and Facial Line Outcomes Questionnaire items. These represent additional perspectives, but the numerical results for those measures are not described in the posted outcome details available in the registry record. No conclusions about their observed results should be inferred from the outcomes’ inclusion in the list.
Unadjusted secondary results carry less weight for confirmatory interpretation when several outcomes and comparisons are considered. In general, multiple testing raises the chance of finding at least one apparently notable result by chance, and no multiplicity adjustment is reported in the registry record. The secondary findings can be read as complementary descriptions of the observed pattern, while the primary endpoint remains the outcome identified as primary. The full prespecified hierarchy and multiplicity strategy are not reported.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines
- Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile
- Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest
- Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score
- Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline
- Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30
- Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30
- Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30
9. Statistical Interpretation
For the primary endpoint at Day 30, the reported responder percentages were 21.3% in the onabotulinumtoxinA 44 U group, 20.6% in the 24 U group, and 0.0% in the normal saline group. The corresponding responder counts were 65 of 305, 63 of 306, and 0 of 306. These are the posted group results for the composite assessment of crow’s feet lines at maximum smile.
The registry reports an unadjusted p < 0.001 for each comparison of an onabotulinumtoxinA group with normal saline. A p-value measures how compatible the observed data are with a specified null hypothesis under the assumptions of the test; it is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The record’s posted p-values are unadjusted, so they should be read as individual comparison results rather than as evidence that accounts for all outcomes or comparisons.
The observed percentages are close between the two onabotulinumtoxinA groups, while both are above the reported percentage in the saline group. These are descriptive comparisons; they do not establish a difference between the two active-dose groups. The posted primary comparisons are each against placebo, and no direct statistical comparison between the two onabotulinumtoxinA groups is reported in the registry record.
The primary endpoint is defined by a threshold of at least a 2-grade improvement. Participants just reaching that threshold and those improving by more grades are both counted as responders. Conversely, participants who improved by less than the threshold are not counted as responders. The percentages therefore answer a specific threshold question and do not summarize the full range of individual changes.
Interpretation is also tied to the endpoint’s population and missing-data rule: all randomized participants were included in the intent-to-treat population, and participants with missing primary values were considered non-responders. The registry record does not report how many primary values were missing or describe sensitivity analyses for alternative missing-data assumptions. The stated result should be understood in the context of that rule and the Day 30 measurement, not as a complete account of later outcomes or all aspects of safety.
10. Statistical Methods Explained
The main reported outcome is a binary percentage: the fraction of participants in a group who met the responder definition. The definition was at least a 2-grade improvement from baseline on the composite Investigator and Subject assessment of crow’s feet line severity at maximum smile. The registry reports group sizes, responder percentages, and responder counts for each randomized group. This makes the endpoint directly interpretable as the observed proportion meeting the predefined threshold in each group.
What does an unadjusted comparison mean?
The registry reports risk-difference comparisons of each onabotulinumtoxinA group with normal saline, with unadjusted p-values. In general, a risk difference expresses the difference between two group proportions. The unadjusted label means the reported comparison is not described as having an adjustment for other variables or for multiple comparisons. It does not establish that no adjustment was planned in a separate statistical plan; that plan is not reported in the registry record.
The posted comparisons use the placebo group as the reference for each active group. The results do not report a test of the 44 U group directly against the 24 U group. A numerical similarity between two observed group percentages is not a substitute for a direct comparison, and a conclusion about whether the active regimens differ from each other is not supported by these placebo comparisons alone.
How should the p-values be read?
In general, a p-value describes how unusual data at least as incompatible with a null hypothesis as the observed data would be, if that null hypothesis and the test assumptions held. It does not give the probability that the null hypothesis is true. Nor does a small p-value indicate how large an observed difference is. The group percentages and the interval estimates address the observed magnitude and its uncertainty; the p-value addresses a different question about compatibility with a null comparison.
The primary results report p < 0.001 for both comparisons with normal saline. The record identifies these as unadjusted. No multiplicity procedure or adjusted primary p-value is reported. The absence of a reported adjustment matters when interpreting a collection of endpoints and comparisons, because examining several results can increase the chance of at least one small p-value under a set of null hypotheses. This general issue does not change the reported values, but it limits treating each unadjusted secondary result as if it were an isolated confirmatory test.
What role does the analysis population play?
The primary analysis population is described as intent-to-treat and includes all randomized participants. The stated rule counts missing primary values as non-responders. In general, this approach preserves the randomized group assignment in the analysis and makes the handling of missing primary values explicit. It also means that a participant’s missing result contributes to the non-responder count rather than being excluded from the endpoint percentage. The registry record does not report the number of missing primary measurements or additional analyses examining other assumptions about missing values.
The record does not describe an adjusted regression model, stratification factors, covariate adjustment, the test used to calculate the p-values, or the procedure used to form confidence intervals. Those methods should not be inferred merely from the labels for the reported risk differences and p-values. The statistical analysis plan is not reported in the registry record.
What do the planning illustrations represent?
Some posted secondary comparisons include planning illustrations based on a stated fraction of the observed effect. The registry’s note describes these as illustrations, not the trial’s own sample-size design. In general, a planning calculation estimates the number of participants needed under specified assumptions to detect a chosen effect with a chosen power. Such calculations depend on assumptions about the effect, allocation, significance level, and statistical approximation. The stated illustrations use a two-sided significance level of 0.05, equal allocation between two groups, and a normal approximation. They are not observed power, do not show what power the completed trial achieved, and should not be treated as the documented justification for enrolling 917 participants.
The registry record does not report a sample-size justification for the trial, interim analyses, or a complete analysis plan. It also does not report whether any planned analyses were changed. The posted figures therefore support description of the stated outcomes and comparisons, but not reconstruction of unreported design decisions or inferential procedures.
11. Confidence Intervals and Precision
A confidence interval gives a range of values compatible with the data and the interval method, under its assumptions. In general, a narrower interval indicates greater precision for the estimated quantity, while a wider interval indicates more uncertainty. An interval is not a guarantee that the true value lies within its particular bounds, nor does it describe the range of individual participant outcomes.
The registry posts interval estimates for the primary risk-difference comparisons, along with the group percentages and unadjusted p-values. The reported direction of each comparison is consistent with the observed group percentages: the active-group responder proportions are above the saline-group proportion. The interval estimates provide information about uncertainty in those group contrasts that the point estimates alone cannot convey. The confidence-interval method is not reported in the registry record, so details of its assumptions cannot be assessed from the record.
The primary group sizes were 305, 306, and 306 participants. Those denominators matter when judging precision: an estimate from a finite group is subject to sampling variability, even when the observed percentage is clear. The confidence intervals concern the estimated group contrast and should be considered alongside the endpoint definition, the missing-as-non-responder rule, and the fact that the comparisons are unadjusted.
Precision does not settle every interpretive question. A confidence interval around a group contrast does not establish the clinical importance of the endpoint threshold, address unreported outcomes, or show whether the two active regimens differ from each other. The registry’s primary interval estimates are available, but the registry record does not report the interval construction method or a multiplicity adjustment. These limits should be kept in view when interpreting the apparent separation between the placebo and active groups.
12. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary outcome and lists eight secondary outcomes. The posted comparison results include unadjusted p-values. A multiplicity adjustment, testing hierarchy, or other method for controlling the overall error rate across endpoints and treatment comparisons is not reported in the registry record. In general, when many hypotheses are tested, the chance of at least one small p-value under null conditions can be greater than for a single test. This is why unadjusted secondary p-values are usually interpreted more cautiously than a result from a clearly specified primary test.
The primary population is described as intent-to-treat, including all randomized participants. For the primary endpoint, missing values were considered non-responders. This is a stated endpoint rule, not a claim that primary data were complete. The registry record does not report the number of participants with missing primary values, reasons for missingness, or sensitivity analyses using alternative assumptions. Missing-data handling for the secondary outcomes is not reported in the registry record.
The record does not report the full statistical analysis plan, a prespecified sequence for testing endpoints, or whether any analyses were designated as exploratory. It also does not report interim analyses. Without those details, it is not possible to determine from the registry record how the investigators intended to manage multiplicity, or whether the posted analyses fully match the original plan. These omissions do not alter the reported outcome values, but they limit assessment of the broader inferential framework.
The primary result should therefore be read using its explicit definition and missing-value rule, and secondary findings should be treated as additional, unadjusted comparisons. This distinction is important: the number of outcomes and comparisons affects the interpretation of statistical evidence, even when each individual outcome is clearly defined.
13. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| onabotulinumtoxinA 44U | 5 | 305 | 1.6% |
| onabotulinumtoxinA 24U | 8 | 306 | 2.6% |
| Placebo (Normal Saline) | 6 | 306 | 2.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| onabotulinumtoxinA 44U | 58 of 305 |
| onabotulinumtoxinA 24U | 51 of 306 |
| Placebo (Normal Saline) | 38 of 306 |
Most frequent serious adverse event terms
| Event term | Organ system | onabotulinumtoxinA 44U | onabotulinumtoxinA 24U | Placebo (Normal Saline) |
|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 305 | 3 of 306 | 0 of 306 |
| Myocardial infarction | Cardiac disorders | 0 of 305 | 1 of 306 | 1 of 306 |
| Pneumonia | Infections and infestations | 1 of 305 | 0 of 306 | 1 of 306 |
| Goitre | Endocrine disorders | 0 of 305 | 1 of 306 | 0 of 306 |
| Non-cardiac chest pain | General disorders | 1 of 305 | 0 of 306 | 0 of 306 |
| Cholecystitis | Hepatobiliary disorders | 0 of 305 | 0 of 306 | 1 of 306 |
| Herpes zoster | Infections and infestations | 1 of 305 | 0 of 306 | 0 of 306 |
| Breast cellulitis | Infections and infestations | 0 of 305 | 1 of 306 | 0 of 306 |
| Urosepsis | Infections and infestations | 0 of 305 | 1 of 306 | 0 of 306 |
| Cellulitis | Infections and infestations | 0 of 305 | 0 of 306 | 1 of 306 |
Most frequent non-serious adverse event terms
| Event term | Organ system | onabotulinumtoxinA 44U | onabotulinumtoxinA 24U | Placebo (Normal Saline) |
|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 24 of 305 | 18 of 306 | 15 of 306 |
| Headache | Nervous system disorders | 19 of 305 | 14 of 306 | 18 of 306 |
| Injection site haematoma | General disorders | 15 of 305 | 19 of 306 | 5 of 306 |
Serious events with the highest arm-level rate: basal cell carcinoma (1.0%), non-cardiac chest pain (0.3%), pneumonia (0.3%), herpes zoster (0.3%), syncope (0.3%).
The registry reports serious adverse events in 5 of 305 participants in the onabotulinumtoxinA 44 U group, 8 of 306 in the 24 U group, and 6 of 306 in the normal saline group. Other adverse events were reported for 58 of 305, 51 of 306, and 38 of 306 participants, respectively. These are counts among the stated numbers at risk; they are not estimates of causality or measures of severity for the non-serious events.
The listed serious adverse event terms include basal cell carcinoma at 1.0%, and non-cardiac chest pain, pneumonia, herpes zoster, syncope, and myocardial infarction at 0.3% each. The registry record does not specify in this summary how these terms were distributed across groups or establish whether an event was caused by treatment. Death counts are not reported in the registry record; their absence from the displayed values should not be interpreted as confirmation that no deaths occurred.
Safety counts should be read alongside the trial’s group sizes and the scope of the registry reporting. They do not, by themselves, establish comparative risk or provide a full account of timing, duration, seriousness criteria, or participant-level event histories.
14. What the Result Does, and Does Not, Mean
The primary result describes the proportion of randomized participants who met a specific responder threshold at Day 30. It reports higher responder percentages in both onabotulinumtoxinA groups than in the normal saline group under the stated composite assessment and missing-data rule. The posted unadjusted comparisons also report p < 0.001 for each active-group comparison with saline.
This result does not mean that every participant receiving an active regimen improved, or that every participant in the saline group had no improvement. The percentages classify participants according to a defined threshold; they do not show the full range of individual changes. The endpoint also concerns crow’s feet line severity at maximum smile at a particular assessment time, rather than every facial line outcome, every time point, or every aspect of participant experience.
The primary endpoint combines Investigator and Subject Facial Wrinkle Scale assessments. It is not a measure based on only one of those perspectives. The two active regimens were each compared with saline in the posted primary comparisons, but a direct statistical comparison between the active regimens is not reported. Similar observed responder percentages do not establish equivalence or prove that the regimens have the same effect.
Statistical significance is not the same as clinical importance. The registry record does not provide a threshold for what magnitude of between-group difference would be considered clinically important, nor does the primary endpoint alone answer questions about duration, other outcomes, or safety. The confidence intervals describe uncertainty in the reported comparisons, but their construction method is not reported.
Finally, the findings apply to the registered trial population, intervention descriptions, comparator, and endpoint definition. The registry does not report all details needed to assess generalizability, the full analysis plan, or missingness beyond the stated primary rule. The results should be understood within those boundaries rather than extended to unreported outcomes or populations.
15. Why This Trial Matters Statistically
This trial illustrates why an endpoint’s definition matters as much as its label. The primary outcome is not simply a general assessment of improvement: it specifies a composite of Investigator and Subject ratings, a maximum-smile assessment, a Day 30 time point, and a threshold of at least a 2-grade improvement. Those choices determine which participants count as responders and what the resulting percentages mean.
It also shows how a binary outcome can communicate a clinically interpretable threshold while concealing variation within each category. A participant just reaching the response threshold and a participant with a larger change both contribute to the responder percentage. Reading the proportion together with the stated endpoint avoids treating it as a complete description of every participant’s experience.
The record also gives a practical example of the distinction between primary and secondary evidence. The secondary outcomes use different assessments and thresholds, and their posted comparisons are unadjusted. Their broad direction can add context, but a collection of nominal results does not replace a prespecified multiplicity strategy or a direct comparison between active regimens. The missing reporting of that strategy limits how strongly the secondary findings can be treated as confirmatory.
Finally, the registry separates observed results from planning illustrations. Calculations based on observed effects can help illustrate sample-size assumptions, but they are not the trial’s own sample-size justification and are not observed power. The record does not report the trial’s original sample-size rationale. Keeping that distinction clear prevents a retrospective illustration from being mistaken for a design decision documented before the trial.
16. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
- Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.
The registry record does not report the full eligibility criteria, detailed randomization procedure, allocation concealment, or who was masked. It identifies the trial as randomized and double-masked, but those labels alone do not establish how these procedures were implemented. The record also does not report the full statistical analysis plan, sample-size justification, interim analyses, or a multiplicity strategy.
For the primary endpoint, missing values were treated as non-responses, but the number and reasons for missing values are not reported in the registry record. Sensitivity analyses under alternative missing-data assumptions are also not reported. This limits assessment of how the primary result might depend on the stated missing-value rule. Handling of missing values for secondary outcomes is not reported.
The posted primary comparisons are each against normal saline. A direct inferential comparison between the 44 U and 24 U groups is not reported, so their observed percentages should not be used to claim that one regimen is superior, equivalent, or non-inferior to the other. The reported p-values are unadjusted, and no multiplicity procedure is documented.
The registry’s secondary outcome list covers more measures than the numerical secondary details described in the record. Results for several listed participant-reported and questionnaire measures are not reported in the registry record. The safety summary provides group counts and selected serious adverse event terms but does not provide a complete account of event timing, duration, or treatment attribution. Death counts are not reported in the registry record.
These reporting limits do not invalidate the posted results, but they restrict conclusions about methods, missingness, other outcomes, safety details, and generalizability.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines and Frown Lines — NCT01189760.
- Registry record last updated 2019-04-16; status last verified 2019-04.
- Results first posted 2013-12-03.
- 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.
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20. Record Summary
NCT01189760 is a completed randomized, double-masked, parallel phase 3 trial sponsored by Allergan, with 917 participants enrolled. It compared onabotulinumtoxinA 44 U, onabotulinumtoxinA 24 U with placebo, and normal saline for crow’s feet and frown lines. Each group’s treatment description specifies injections into bilateral crow’s feet line and frown line areas and two treatments 4 months apart.
The primary outcome was the percentage meeting a composite responder definition for crow’s feet line severity at maximum smile at Day 30. A responder had at least a 2-grade improvement from baseline on Investigator and Subject Facial Wrinkle Scale assessments. The reported percentages were 21.3%, 20.6%, and 0.0% across the 44 U, 24 U, and saline groups. Each active-group comparison with saline had an unadjusted p < 0.001.
The registry states that the primary analysis included all randomized participants and counted missing values as non-responses. The full statistical plan, multiplicity approach, sample-size justification, and interim analyses are not reported in the registry record.