Lateral Canthal Rhytides With Medium Depth Chemical Peel With or Without Pretreatment With Botulinum Toxin A: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lateral Canthal Rhytides With Medium Depth Chemical Peel With or Without Pretreatment With Botulinum Toxin A (NCT01586819), a randomized phase 3 study. The primary outcome is Posttreament Results of Chemical Peel if Botox A is Added as Pre-treatment.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 3, randomized study sponsored by Loyola University. The record lists enrollment of 26 and a completed status. It records a start date of 2011-09 and primary completion in 2013-05. The study title calls it a split-face, rater-blinded randomized control trial, but the masking field is listed as none and the model field as parallel. These entries leave uncertainty about how the treatment allocation and ratings were implemented. The record does not explain the discrepancy.

The two listed groups were Botulinum Toxin and Chemical Peel Only. The primary outcome was wrinkle severity using the four-point Facial Wrinkle Severity Scale, with baseline and 12 weeks given as the timeframe. The posted group sizes are 11 for Botulinum Toxin and 14 for Chemical Peel Only. The enrollment figure and group sizes are recorded separately; the registry record does not explain the relation between them or identify an analysis population for the primary result.

The record describes treatment with botulinum toxin before a medium-depth chemical peel compared with chemical peel alone. Its brief summary names Jessner’s peel followed by 35% Trichloroacetic acid. The intervention descriptions include a schedule of follow-up visits for the botulinum toxin group, but a complete account of all visit procedures and timing is not reported in the registry record. Detailed randomization procedures, allocation concealment, the sample-size justification, and the statistical analysis plan are also not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Twenty-six female subjects ages 30 to 75 years old were enrolled in this 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 Posttreament Results of Chemical Peel if Botox A is Added as Pre-treatment, measured over Baseline and 12 weeks.

The primary endpoint is the Facial Wrinkle Severity Scale, a four-point ordinal measure of lateral canthal wrinkle severity. The registry defines Grade 0 as no wrinkles, Grade 1 as mild wrinkles, Grade 2 as moderate wrinkles, and Grade 3 as severe wrinkles. The record names units as scale units and describes the primary outcome as a median with interquartile range. The stated assessment timeframe is baseline and 12 weeks.

An ordinal scale distinguishes ordered categories without requiring that the distance between adjacent grades be equal. For example, moving from mild to moderate severity is an ordered change, but the scale does not establish that this change is numerically equivalent to moving from moderate to severe. Reporting the median and interquartile range is therefore a way to describe the center and spread of ranked scores while retaining the scale’s ordered categories.

The posted median is 1.0 in the Botulinum Toxin group and 2.0 in the Chemical Peel Only group. Their posted interquartile limits are 0.0 to 1.0 and 1.0 to 2.0, respectively. The outcome title refers to posttreatment results, but the record also states baseline and 12 weeks as the timeframe. It does not state whether the posted values are 12-week scores, baseline-adjusted values, or change scores. That distinction matters when interpreting a comparison over time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is summarized with medians and interquartile ranges. A median is the middle of an ordered set of observations. The interquartile range describes the central half of the distribution, so its lower and upper limits indicate where that central portion begins and ends. General statistical point: for an ordinal scale, these summaries preserve the order of categories and avoid treating the difference between successive grades as necessarily equal. In this study, the scale runs from Grade 0, no wrinkles, through Grade 3, severe wrinkles.

The record reports a Wilcoxon (Mann-Whitney) test. General statistical point: this rank-based method compares the ordering of observations between two groups. It does not require the scores to follow a normal distribution, an assumption that may be difficult to justify for a short ordinal scale. The test is often interpreted as assessing whether observations from one group tend to rank differently from observations in the other group. It does not directly estimate a difference in medians in every setting; interpretation depends on the shape and spread of the group distributions as well as their locations.

The registry reports p = .002 for the test. General statistical point: a p-value is calculated under a null hypothesis and a set of model assumptions. It describes how unusual data at least as incompatible with the null model would be if that model and those assumptions held. It is not a measure of the probability that the null is true, and it does not state the chance that the result will replicate. A p-value also does not communicate the size of the group contrast or its precision. A confidence interval for an effect estimate would address precision more directly, but no such interval is reported for this outcome.

The record’s description of the design creates an important analysis question. The official title calls the trial split-face and rater-blinded, while the masking field says none and the model field says parallel. A split-face design generally means that treatments are assigned to different sides of the same participant, so two measurements from that participant can be correlated. General statistical point: paired methods preserve the relationship between within-person observations, whereas a test for independent groups assumes observations across groups are independent. The registry’s named Mann-Whitney method is a two-group rank test, but the record does not explain whether the analysis used paired observations, participant-level summaries, or another approach. It is not possible to determine from the record whether the analysis accounts for the design described in the title.

The primary endpoint is stated to be assessed at baseline and 12 weeks, but only one set of arm medians and interquartile limits is posted. The record does not identify those values as baseline scores, 12-week scores, or changes from baseline. Nor does it describe a model that adjusts for baseline score or explains how repeated measurements were handled. This omission makes it difficult to interpret the posted values as a treatment effect over time rather than a simple description of scores at a particular assessment.

Sample-size planning information is not reported as part of the trial’s own design justification. The record does describe planning illustrations based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are planning calculations, not observed trial outcomes and not evidence of the probability that this completed trial detected an effect. The registry record does not report the original target sample size rationale, assumptions about the expected effect, or any adjustment for the described study structure.

There is no reported confidence interval for the group contrast, and no adjusted effect estimate is listed. The record also does not specify whether the reported analysis was prespecified, which analysis population was used, how missing outcome measurements were handled, or whether sensitivity analyses were conducted. These omissions do not alter the numerical summaries or the reported p-value, but they limit assessment of precision, robustness, and the alignment of the analysis with the trial design.

General statistical point: a sound interpretation combines the measurement scale, analysis method, design, effect estimate, and uncertainty. Here, the rank-based method and the ordinal endpoint can be understood from the registry, but important design and analysis details are not. In particular, the title’s split-face description and the lack of an explicit pairing explanation make the test’s assumptions difficult to evaluate. The reported result should therefore be read as the analysis recorded in the registry, with those limitations in view.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s Wilcoxon (Mann-Whitney) analysis and p = .002. It gives a Z statistic as part of that result, but no confidence interval or numerical treatment-effect estimate. The reported arm summaries are medians of 1.0 for Botulinum Toxin and 2.0 for Chemical Peel Only, with interquartile limits of 0.0 to 1.0 and 1.0 to 2.0, respectively.

No independent recalculated contrast or p-value is specified in the registry record, so there is no separate recalculation to compare numerically with the sponsor’s analysis. The record does not flag a discrepancy. If a recalculated analysis and the sponsor’s analysis differ, the sponsor’s own analysis takes precedence for describing the registered result; the assumptions and study design still need to be considered when interpreting it. In this case, the registry does not explain whether the Mann-Whitney test accounts for the split-face description in the title, nor does it clarify whether the posted values represent week-12 scores or changes from baseline. Those uncertainties are not resolved by the reported p-value.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, but it does not report a multiplicity adjustment or explain how the primary analysis was selected among any planned analyses. It also does not state whether there were prespecified secondary outcomes, subgroup comparisons, or additional time points included in the analysis plan. The record therefore does not establish how many statistical tests were planned or whether the reported p-value was adjusted for multiple testing.

General statistical point: when many hypotheses are tested, the chance of obtaining at least one small p-value under a collection of null hypotheses can increase. Adjustment procedures can address that issue, but the appropriate approach depends on the planned family of tests and the analysis strategy. Since the registry does not describe that strategy, the impact of multiplicity on the reported result cannot be assessed from this record.

The registry does not report missing-data counts for the primary endpoint, explain how missing observations were handled, or identify whether the analysis included all randomized participants or another analysis population. The posted arm sizes are 11 and 14, while overall enrollment is recorded as 26; the record does not explain the relationship between these counts. No conclusion about exclusions or missingness can be drawn from those figures alone.

The record also does not state whether the analysis was intention-to-treat, per-protocol, or based on another population definition. It gives no details about imputation, sensitivity analyses, or the handling of any participants who did not complete the stated assessment timeframe. These omissions matter because missing outcomes and analysis-population choices can affect which observations contribute to a comparison.

12. 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 0% reporting threshold.

The registry reports serious adverse events for 0 of 11 participants at risk in the Botulinum Toxin group and 0 of 14 participants at risk in the Chemical Peel Only group. Deaths are recorded as 0 in both groups. The registry also records other adverse events for 0 of 11 and 0 of 14 participants at risk, respectively.

These figures describe the counts recorded in the registry for the stated groups and at-risk denominators. They do not establish that no adverse events of any kind occurred outside the categories or reporting period represented in the record. The registry does not provide event terms for serious adverse events, and the serious-event term list is empty. It also does not describe the event-collection methods or the time window used for safety reporting.

Zero reported events should be interpreted as no events recorded in those categories for the listed participants, not as proof that the risk is absent. The figures are descriptive and do not provide a precise comparative estimate of safety between groups. The record does not report a statistical comparison of adverse events.

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

The posted primary outcome summaries show a median wrinkle severity score of 1.0 in the Botulinum Toxin group and 2.0 in the Chemical Peel Only group. The scale defines lower grades as less severe wrinkles. The registry reports a Wilcoxon (Mann-Whitney) test with p = .002. Together, these entries describe the observed scores and the sponsor-reported rank-based statistical test.

They do not provide a complete estimate of the size or precision of the treatment contrast. No confidence interval is reported, and the registry does not give a separate effect estimate beyond the group summaries. The record also does not clarify whether the posted scores refer to the 12-week assessment or change from baseline. It therefore cannot establish from these entries alone how much scores changed during follow-up.

The title describes a split-face, rater-blinded randomized trial, but the registry’s masking and model fields do not match that description. The record does not say whether the reported Mann-Whitney analysis accounted for within-participant pairing. That uncertainty limits assessment of whether the statistical method reflects the design described in the title.

The p-value is not a measure of clinical importance, and it does not establish that the finding would be replicated in another study. The adverse-event counts record no serious or other events in the listed groups, but they do not establish that risk is absent. Overall, the registry offers a comparison of wrinkle-severity summaries and a reported test, while leaving unanswered questions about the endpoint values, analysis structure, missing data, and precision. The result should be read within those limits and not as medical advice.

14. Why This Trial Matters Statistically

This trial raises a useful statistical issue because the registry presents an ordinal outcome and describes the study as split-face. An ordinal wrinkle scale is not the same as a continuous measurement with equal intervals between values. Medians, interquartile ranges, and rank-based tests can describe ordered outcomes without requiring a normal distribution, but their interpretation still depends on how the observations were collected and related to one another.

The design description makes that relationship especially important. If each participant contributes observations from both sides of the face, those observations may be paired. The registry’s title uses split-face language, while the listed model is parallel, and the reported Mann-Whitney method is not accompanied by an explanation of how any paired structure was handled. This makes the connection between design and analysis a central question for readers.

The trial also illustrates why a p-value is not a complete report of an effect. The registry includes group medians, interquartile limits, and a p-value, but no confidence interval or separate numerical estimate of the contrast. It also does not identify whether the scores are posttreatment values or changes from baseline. Statistical interpretation depends not only on whether a test result is small, but also on the outcome definition, time point, analysis method, and uncertainty.

Finally, the difference between the overall enrollment entry and the group sizes cannot be interpreted without a participant flow or analysis-population description. The record does not state whether any outcomes were missing or how they were handled. These are practical reminders that a registry result can be informative while still leaving essential questions about design implementation and analysis unresolved.

15. 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 contains inconsistent design descriptions: the official title calls the study split-face and rater-blinded, but the masking field says none and the model field says parallel. It does not explain how randomization was implemented, whether treatment was assigned by facial side, or whether ratings were blinded. These details are important for judging the risk of bias and the appropriateness of the analysis.

The primary outcome timeframe is baseline and 12 weeks, but the record posts one set of medians and interquartile limits without identifying whether they are baseline values, week-12 values, or changes. It does not provide a confidence interval or a distinct estimate of the treatment contrast. As a result, the magnitude and precision of the comparison cannot be fully evaluated from the posted statistics.

The reported Mann-Whitney analysis is not accompanied by an explanation of how the test relates to the split-face title description. The registry does not report the analysis population, the number of participants contributing to each outcome analysis, missing-data handling, or sensitivity analyses. Although enrollment and arm counts are recorded, the record does not explain their relationship.

The sample-size justification and prespecified statistical analysis plan are not reported in the registry record. Nor does it describe any multiplicity strategy, interim analyses, or the rationale for selecting the reported test. The safety record gives zero counts for the listed event categories but does not describe ascertainment procedures or provide event terms. These limitations concern what can be evaluated from the registry record; they do not determine the results beyond the statistics that are posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lateral Canthal Rhytides With Medium Depth Chemical Peel With or Without Pretreatment With Botulinum Toxin A — NCT01586819.
• Registry record last updated 2017-09-11; status last verified 2017-08.
• Results first posted 2017-09-11.
• 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.

19. Record Summary

NCT01586819 is a completed Phase 3 randomized study sponsored by Loyola University, with enrollment recorded as 26. It compares botulinum toxin pretreatment before a medium-depth chemical peel with chemical peel only for lateral canthal rhytides. The primary endpoint is the four-point Facial Wrinkle Severity Scale, with baseline and 12 weeks listed as the timeframe.

The registry posts medians of 1.0 for Botulinum Toxin and 2.0 for Chemical Peel Only, and reports a Wilcoxon (Mann-Whitney) test with p = .002. It records no serious adverse events, other adverse events, or deaths in either listed group. Interpretation is limited by unresolved differences in the design descriptions, uncertainty about what the posted endpoint values represent, and the absence of a confidence interval, analysis-population details, and missing-data information.