Study of BOTOX and JUVEDERM for Treatment of Moderate to Severe Facial Wrinkles and Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of BOTOX and JUVEDERM for Treatment of Moderate to Severe Facial Wrinkles and Folds (NCT01269801), a randomized phase 4 study. The primary outcome is Efficacy.

2. Clinical Question

3. Trial Design

This was a Phase IV, randomized, open-label crossover study. It enrolled 156 participants and is listed as completed. The registry records a start in 2011-01 and primary completion in 2011-09. The sponsor was AboutSkin Dermatology and DermSurgery, PC. Wrinkles are the listed condition.

The treatments were BOTOX Cosmetic, described as onabotulinumtoxinA for injection, and JUVÉDERM, described as JUVÉDERM Ultra XC and JUVÉDERM Ultra Plus XC Injectable Gel. The brief summary says the study aimed to compare these products with each other and when used together. The registry record does not give the treatment sequence, the interval between treatment periods, or details of how the combined treatment was administered.

In a crossover design, treatment order matters because participants may receive more than one treatment strategy over time. Such designs can support within-participant comparisons, but their interpretation depends on details such as sequence assignment, timing, and whether effects from an earlier period can persist into a later one. Those design details are not reported in the registry record, so the specific crossover structure cannot be reconstructed from the available description.

Masking is listed as none, meaning the study is described as open label. The record does not say whether outcome assessors were masked separately from participants or treating clinicians. It also does not report the number assigned to each sequence or whether all enrolled participants contributed data at each assessment. The stated analysis population is based on randomization group to account for the order in which products were administered, but no further analysis details are reported.

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: Subjects were randomized to two groups: Juvederm first, then Botox (Juvederm group) or Botox first, then Juvederm (Botox group). For the Juvederm group, Day 1 involved juvederm treatment. Week 4 involved botox administration. For the Botox group, Day 1 involved botox treatment. Week 4 involved juvederm administration.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis is based on the randomization group to account for the order in which the products were administered.

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 analysis stratified by treatment group (per sequence).

6. Primary Endpoint

The registry lists the primary outcome as Efficacy, measured over Week 4, 8, 12, 24.

The primary outcome is labeled efficacy and concerns the number of participants with improvement from baseline on aesthetic improvement ratings. The description identifies the Physician Global Aesthetic Improvement Scale (PGAIS) and the Objective Observer Global Aesthetic Improvement Scale. The PGAIS categories listed are no change, improved, much improved, and very much improved. The observer scale categories are no change, some improvement, definite improvement, substantial improvement, and complete improvement.

Assessments are listed at weeks 4, 8, 12, and 24, corresponding to Visits 3, 5, 6, and 7. The primary description specifically refers to participants with an improvement score from baseline to Visit 7. The record describes PGAIS as a five-point scale but lists four category labels; the exact scale definition and the rule for classifying a participant as improved or better are not fully reported in the registry record.

Global aesthetic ratings are used to describe perceived change relative to baseline in a structured way. A count of participants meeting an improvement definition can be clinically interpretable, but it compresses the degree of change into a category and depends on how improvement is defined and assessed. The registry record does not report the observed counts or explain how ratings from the physician and objective observer scales were combined, if at all.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to reduce systematic differences between treatment assignments at the outset. In this study, the record identifies randomized allocation and a crossover model. In a crossover design, participants may contribute observations under more than one treatment period, so the order in which treatments are received is part of the design. The record states that the analysis is based on the randomization group to account for product order. It does not describe the allocation sequences, period structure, or the statistical model used to analyze repeated observations.

What does crossover mean for interpretation?

As a general statistical matter, crossover studies can compare treatments within participants, which may reduce variability from stable differences between people. This advantage depends on appropriate design and analysis. Outcomes can be affected by period effects, learning or assessment effects, and carryover, in which a prior treatment continues to influence a later observation. The registry record does not report whether a washout period was used, whether carryover was assessed, or how period effects were handled. These omissions prevent readers from judging how the design addressed those concerns.

The study is open label, with masking listed as none. As a general matter, knowledge of treatment can influence subjective assessments, participant reporting, or clinical decisions. The outcome description includes both a physician rating and an objective observer rating, but the record does not say whether assessors were masked or how the observer scale was operationalized. The word “objective” in the scale title does not by itself establish that assessment was free from knowledge of treatment or other sources of bias.

How should the improvement outcome be understood?

The endpoint is a count of participants with improvement ratings from baseline. The description identifies the PGAIS and the Objective Observer Global Aesthetic Improvement Scale, with assessments at weeks 4, 8, 12, and 24. Such ratings are ordinal: categories indicate an order of perceived improvement, but the distance between adjacent categories is not necessarily equal. A binary count of participants improved or better can make results easier to interpret, but it discards information about how far participants moved across the scale.

The registry description does not fully specify the threshold used to classify improvement, nor does it explain whether each scale had a separate primary analysis or whether results were combined. It describes the PGAIS as five point while listing four category labels. A reproducible analysis would require an unambiguous scale definition, the scoring rule, the chosen time point, and a clear account of how missing or incomplete ratings were handled. Those details are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under the statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, although precision does not resolve bias or establish that the model is appropriate. The registry record does not report an efficacy estimate or confidence interval, so neither the direction nor the precision of the primary comparison can be assessed.

A p-value, when used, addresses how unusual data at least as incompatible with a specified null hypothesis would be under the model. It does not measure the probability that a treatment effect is real, and it does not describe the size or importance of an effect. No efficacy p-value or statistical test result is reported in the registry record. The record also does not report the planned significance threshold for the primary efficacy analysis.

Why do over-dispersion and model choice matter?

As a general explanation, count outcomes can vary more than a simple statistical model expects. This is called over-dispersion. If present and ignored, uncertainty estimates may be too optimistic. However, the primary outcome is described as a number of participants with improvement, and the registry does not report the distribution of the data or the model used. There is therefore no basis to say that over-dispersion occurred or that a particular count model was used. For a binary participant-level outcome, methods for comparing proportions or modeling repeated crossover observations may be relevant, but the analysis actually selected is not reported.

The sample-size planning assumptions state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe planning for fractions of the observed effect. These are planning assumptions, not evidence about the trial's original design or its achieved ability to detect an effect. The record does not report the trial's own sample-size justification, and planning values are not observed power. Because the primary outcome is not reduced to one comparison in the registry data, a single observed effect for such planning is not described in the record.

Finally, the registry lists zero analyses. This means the record does not contain analysis entries for the outcome in the information at hand; it does not establish that no analysis was performed outside the registry. Without an analysis report, readers cannot assess the handling of repeated measures, treatment order, missing observations, or uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The primary description includes assessments at weeks 4, 8, 12, and 24 and names two aesthetic improvement scales. Multiple visits and scales create the possibility of multiple statistical comparisons. As a general matter, if many comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan specifies a primary contrast or accounts for multiplicity. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which scale and visit were designated for a primary inferential comparison.

The registry names Visit 7 as the baseline-to-follow-up point for the participant improvement count, while also listing assessments at earlier visits. It does not say whether those earlier assessments were secondary, exploratory, or part of a repeated-measures analysis. The exact improvement threshold and any rules for combining physician and observer ratings are also not fully reported. These gaps make it difficult to know which result should be considered the principal efficacy finding even if results were available.

Missing-data methods are not reported in the registry record. The entry does not state how participants without a Visit 7 assessment, incomplete ratings, or withdrawal were handled. Nor does it describe imputation, sensitivity analyses, or a complete-case approach. The enrolled population is listed as 156, but the number contributing to each efficacy assessment is not reported.

The analysis population is described as based on randomization group to account for treatment order. The record does not give further definitions, such as whether all randomized participants were included or how deviations from assigned order were treated. Accordingly, an intention-to-treat analysis, a per-protocol analysis, or any other specific population should not be inferred.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death due to hypertensive cardiovascular disease (0.6%).

The registry lists serious adverse event information separately for the two named groups. For Botox Cosmetic, it records 154 at risk and 1 affected by a serious adverse event; for JUVÉDERM, it records 152 at risk and 0 affected. The record also lists other adverse events: 8 affected in the Botox Cosmetic group and 19 in the JUVÉDERM group, with the corresponding at-risk counts recorded as 154 and 152.

These entries are counts as posted in the registry, not an adjusted comparison. The record does not report the statistical method for comparing safety outcomes, event timing, severity details beyond the serious-event classification, or how attribution was handled across treatment periods in the crossover design. The figures should not be interpreted as rates calculated from the counts or as proof of a difference between treatments.

The serious-event term listed is “death due to hypertensive cardiovascular disease” at 0.6%. The deaths field for the listed groups is null, and the registry record does not explain how the term relates to the group-level serious-event counts or deaths information. The term should therefore be read as a registry entry whose context is not fully described, rather than as a reconciled account of deaths in each group.

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

The record describes a completed Phase IV randomized crossover study with an enrollment of 156 and a primary efficacy outcome based on aesthetic improvement ratings. It also provides group-level adverse-event entries. These details are useful for understanding the study's question and the kinds of outcomes it tracked, but they do not provide the efficacy findings needed to estimate a comparative treatment effect.

No primary outcome counts, effect estimates, confidence intervals, or efficacy test results are reported in the registry record. It is therefore not possible to say how many participants improved, whether one strategy had a larger improvement count, or how precise any difference was. The study's completed status is a status designation, not evidence of efficacy or safety.

The results cannot establish equivalence or absence of an effect. A lack of reported comparative results is different from an analysis showing that treatments were similar. Likewise, the listed adverse-event counts do not, on their own, establish that one product is safer. Crossover order, event attribution, missing outcomes, and the analysis population all matter to interpretation, and key details about those matters are not reported.

The endpoint also relies on rating categories. Its interpretation depends on the precise improvement threshold, the assessor, the scale, and the assessment time. The registry names two scales and multiple visits but does not fully define how these elements formed the primary comparison. Any broader claim about magnitude or durability of improvement would go beyond the information in the record.

In short, this registry information supports a description of the trial design, planned efficacy measurement, and posted safety counts. It does not support a conclusion that either treatment strategy produced greater improvement, a quantified claim about the size of a difference, or a clinical recommendation.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining randomized allocation with a crossover design and an outcome based on rated aesthetic change. That combination makes treatment order important: participants may be assessed across periods, and the analysis needs to account for how products were administered. The registry explicitly notes that the analysis population is based on randomization group to account for order, but it does not report the model or sequence details needed to evaluate that approach.

The primary measure is also not a single plainly defined numeric score in the registry description. It refers to participant counts with improvement on physician and observer scales, across several visits. This highlights a general issue in clinical-trial interpretation: outcome definitions need to identify the scale, threshold, assessor, and time point before a count can be understood as a reproducible comparison. Here, those details are incomplete and no efficacy results are posted.

The study illustrates why a completed trial entry and a stated endpoint are not substitutes for results. Without outcome counts and uncertainty estimates, readers cannot assess the size or precision of a treatment contrast. Without a reported analysis plan, they cannot evaluate choices about treatment period, repeated observations, multiplicity, or missing data.

The safety entries provide another statistical lesson. Group counts are descriptive, but an interpretable comparison requires clear definitions, denominators, event attribution, and suitable analysis. The registry's serious-event term and null deaths fields are not reconciled in the record. Careful reading means preserving that ambiguity rather than resolving it by assumption.

14. 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 main limitation of the registry information is the absence of primary efficacy results. Although the study is marked completed and the primary outcome is described, the record does not report improvement counts, comparative estimates, confidence intervals, or efficacy tests. It is therefore not possible to assess the central efficacy question from the posted information.

The endpoint description is incomplete for reproducible interpretation. It names two scales and multiple visits, describes a baseline-to-Visit 7 improvement count, and lists rating categories. It does not fully specify the improvement threshold or how the two scales were used in the primary analysis. The PGAIS is called a five-point scale while four category labels are listed.

Important crossover details are not reported, including treatment sequences, period structure, timing between treatments, and whether carryover was assessed. The open-label designation is clear, but the record does not explain whether outcome assessors were masked. These omissions limit assessment of potential period, order, carryover, and assessment effects.

The registry does not report missing-data handling, a detailed analysis population, a multiplicity plan, or the statistical model. It also does not provide a sample-size justification for the trial. The planning assumptions are not a substitute for the original design rationale or for evidence about the trial's ability to detect an effect.

Safety interpretation is limited by the lack of event timing and comparative analysis details. The serious adverse event term at 0.6% is not reconciled with the group-level deaths fields, which are null. The registry record does not explain that discrepancy in context.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of BOTOX and JUVEDERM for Treatment of Moderate to Severe Facial Wrinkles and Folds — NCT01269801.
• Registry record last updated 2014-12-16; status last verified 2014-12.
• Results first posted 2014-12-16.
• 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.

18. Record Summary

The registry record describes NCT01269801, a Phase IV randomized, open-label crossover study of BOTOX Cosmetic and JUVÉDERM for moderate to severe facial wrinkles and folds. It lists an enrollment of 156, a start in 2011-01, primary completion in 2011-09, and completed status. The sponsor is AboutSkin Dermatology and DermSurgery, PC.

The primary efficacy outcome concerns participant improvement ratings on the PGAIS and Objective Observer Global Aesthetic Improvement Scale, with assessments at weeks 4, 8, 12, and 24. No efficacy results or analysis entries are reported. Safety entries list serious and other adverse events by group, but the record does not provide a comparative safety analysis or reconcile the serious-event term with the deaths fields.