Efficacy and Safety of FS for Flap Adherence in Rhytidectomy ANDREA FIDELL

Study Objectives and Purpose:  Study Purpose: To compare the safety and efficacy of the sealant (FS) versus standard of care (SoC) in adhering tissue and improving wound healing in subjects undergoing face lifts.  Primary Objective: To evaluate the effect of FS on the improvement of flap adherence in subjects undergoing face lifts as indicated by a reduction in drainage volume.

Study Design:  This is a split-face study where one side of the face will be treated with the sealant (FS) and the other side will receive SoC.  Each subject will participate in both arms (FS and SoC) simultaneously, and serve as his/her own control.  The decision of which side of the face will be operated on first, and the decision of which side of the face will receive FS, will both be predetermined by a randomization scheme.  The decisions will be placed in an envelope and opened immediately prior to the start of the surgery. Due to the nature of the product only the subject can be blind to treatment.

Randomization Scheme:  This is a randomized, single-blind, no treatment-controlled clinical study. In order to minimize/avoid bias, subjects will be randomly assigned to 1 of 4 randomization sequences at a ratio of 1:1:1:1.  First FS on the right side and then SoC on the left side.  First FS on the left side and then SoC on the right side.  First SoC on the right side and then FS on the left side.  First SoC on the left side and then FS on the right side.  Doctors should only consider breaking the blind if such knowledge is essential to the subject’s care.

Variables:  The primary efficacy variable is total drainage volume collected on each side of the face at 24 hours (+/- 4h) post-surgery.  Prior to the completion of the surgery of each side, and before the application of FS, a drain will be placed on each side of the face.  The volumes measured for each side of the face will be recorded.

Subject Selection:  Inclusion Criteria:  Subject is years old.  Subject is planned for a face lift.  Subject has read, understood, and signed the written informed consent  Subject is healthy, as determined by doctors using standard preoperative assessments to include laboratory tests.

Subject Selection:  Exclusion Criteria:  Subject is indicated for additional procedure to the body during the same operation.  Subject has undergone a prior face lift surgery.  Subject has known (documented) bleeding or coagulation disorder.  Subject has known sensitivity to sealants.

Results:  I ran a t-test to determine if there was a significant difference between the amount of drainage that came from the FS side of the face and the amount of drainage that came from the SoC side of the face.  My conclusions were based on an alpha level of.05

Histograms of FS and SoC drainage (measured in mL)

Statistical Analysis:  T-test: Is there a significant difference between the amount of drainage on the FS side and the SoC side? Paired Samples Test Paired Differences tdfSig. (2-tailed) MeanStd. DeviationStd. Error Mean 95% Confidence Interval of the Difference LowerUpper Pair 1FS drainage - SOC drainage

More questions…  Does site location have a significant effect on FS drainage?  Does FS dose have an effect on adverse events?  Do surgery duration time, age, and FS dose significantly predict FS drainage?  Are the distributions of BMI, Surgery duration time, and the difference between FS drainage and SoC drainage the same across FS adverse events?  Do additional procedures have a significant effect on FS drainage and SoC drainage while controlling for BMI?  Do BMI and FS dose have a significant effect on SoC drainage and FS drainage?

Statistical Analysis:  ANOVA: Does site location have a significant effect on FS drainage? Tests of Between-Subjects Effects Dependent Variable:FS drainage Source Type III Sum of SquaresdfMean SquareFSig. Corrected Model a Intercept SITEID Error Total Corrected Total a. R Squared =.444 (Adjusted R Squared =.395)

Plot for ANOVA

Statistical Analysis:  ANOVA: Does FS dose have a significant effect on adverse events?

Statistical Analysis:  Regression: Do surgery duration time, age, and FS dose significantly predict FS drainage? ANOVA a Model Sum of SquaresdfMean SquareFSig. 1Regression b Residual Total a. Dependent Variable: FS drainage b. Predictors: (Constant), FS dose (mL), AGE, Surg Dur (hr)

Plots from Regression

Statistical Analysis:  Non-Parametric Tests: Are the distributions of BMI, Surgery duration time, and the difference between FS drainage and SoC drainage the same across FS adverse events? Here adverse events on the FS side of the face is the response variable.

Statistical Analysis:  MANCOVA: Do additional procedures have a significant effect on FS drainage and SoC drainage while controlling for BMI? Multivariate Tests b EffectValueFHypothesis dfError dfSig. InterceptPillai's Trace a Wilks' Lambda a Hotelling's Trace a Roy's Largest Root a BMIPillai's Trace a Wilks' Lambda a Hotelling's Trace a Roy's Largest Root a AddlProcPillai's Trace a Wilks' Lambda a Hotelling's Trace a Roy's Largest Root a a. Exact statistic b. Design: Intercept + BMI + AddlProc Tests of Between-Subjects Effects SourceDependent Variable Type III Sum of SquaresdfMean SquareFSig. Corrected ModelFS drainage a SOC drainage b InterceptFS drainage SOC drainage BMIFS drainage SOC drainage AddlProcFS drainage SOC drainage ErrorFS drainage SOC drainage TotalFS drainage SOC drainage Corrected TotalFS drainage SOC drainage a. R Squared =.023 (Adjusted R Squared = -.005) b. R Squared =.023 (Adjusted R Squared = -.004)

Statistical Analysis:  MANOVA: Do BMI and FS dose have a significant effect on SoC drainage and FS drainage? Is there a significant interaction? Tests of Between-Subjects Effects SourceDependent Variable Type III Sum of SquaresdfMean SquareFSig. Corrected ModelFS drainage a SOC drainage b InterceptFS drainage SOC drainage BMIFS drainage SOC drainage FSdosemLFS drainage SOC drainage BMI * FSdosemLFS drainage SOC drainage ErrorFS drainage SOC drainage TotalFS drainage SOC drainage Corrected TotalFS drainage SOC drainage a. R Squared =.112 (Adjusted R Squared =.075) b. R Squared =.163 (Adjusted R Squared =.127)

Plots from MANOVA