Comparison of Three Botulinum Neuromodulators for Management of Facial Synkinesis
Comparison of Three Botulinum Neuromodulators for Management of Facial Synkinesis
The purpose of this study is to compare the effectiveness of three commercially available
 botulinum toxin neuromodulators in the treatment of facial synkinesis using patient reported
 outcome measures.
Quality assurance:

 Data is entered in to a spreadsheet as it is extracted exactly from the electronic medical
 record. During review of the findings, the data is again checked against the medical record
 to ensure accuracy. Botulinum toxin types are also verified with scanned copies of the
 botulinum toxin injection sheet which is filled out and scanned in to the medical record at
 the time of treatment.

 Data dictionary:

 Not necessary as limited new terminology is used and all understood among the research group.
 Additional terminology is clearly described for the trial participants and described in the
 manuscript reporting the results of the study.

 Recruitment:

 Patients with facial synkinesis who were appropriate candidates for botulinum toxin
 chemodenervation therapy were offered voluntary participation in this trial. Patients who had
 returned to their baseline SAQ score after a minimum of 12 weeks since their previous
 treatment were permitted to re-enroll in the study for subsequent treatments.

 Data collection:

 At 1, 2, and 4 weeks post treatment, patients were again administered the SAQ. SAQ scores
 were calculated for each follow up time point. The average SAQ score in each treatment group
 (onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA) for each week was
 calculated, as well as the average improvement in SAQ scores.

 Data management:

 Data were initially recorded and stored in the secure, password protected, electronic medical
 record. Data were then extracted from the electronic medical record to a secure Excel
 spreadsheet stored on a password protected computer. Only the principal investigator and
 those researchers involved in data analysis and interpretation were provided access to this
 data. Names and identifiable information were excluded from this spreadsheet so that the
 information could not be linked back to specific patients.

 Data analysis:

 Data were analyzed by first organizing the data in Excel, within the original spreadsheet
 used to record data, then exporting this data in to Prism 6 for Windows (GraphPad Software).
 Using Prism 6, characteristics of the data were assessed and statistical calculations were
 performed to determine significance of comparisons between groups. Details of these
 statistical tests are described below.

 Reporting for adverse events:

 Adverse events were recorded in the electronic medical record at each follow-up visit. These
 were then noted in the data spreadsheet as well to keep track of any events that had occurred
 over the study period. Minor adverse effects reported during the study included redness,
 bruising, swelling, and fullness at the injection sites which were not felt to be significant
 or noted to be qualitatively different between products. No major adverse treatment effects
 were reported during the course of the study.

 Change management:

 There were no significant changes to study protocol over the course of the study.

 Sample size assessment to specify the number of participants or participant years necessary
 to demonstrate an effect:

 https://www.dssresearch.com/knowledgecenter/toolkitcalculators/statisticalpowercalculators.as
 px At an alpha level of 0.05, an estimated standard deviation of 10, an estimated average of
 SAQ 44 and comparison/test value of SAQ 55, a sample size was calculated of approximately
 400. We were unable to obtain this sample size after nearly 3 years of enrolment from July
 2012 to March 2015. However, despite not reaching this estimated sample size, we did identify
 a statistically significant finding at alpha level of 0.05 and with a standard deviation of
 approximately 10-15 per group.

 Plan for missing data to address situations where variables are reported as missing,
 unavailable, "non-reported," uninterpretable, or considered missing because of data
 inconsistency or out-of-range results:

 Patients without follow-up at the post-treatment time points of 1, 2, and 4 weeks were
 excluded and therefore no missing data was expected for SAQ values. The plan for any missing
 data in the study was to leave the data point as missing without attempts to imputate the
 value or otherwise correct for missingness.

 Statistical analysis plan describing the analytical principles and statistical techniques to
 be employed in order to address the primary and secondary objectives, as specified in the
 study protocol or plan:

 The average SAQ score in each treatment group (onabotulinumtoxinA, abobotulinumtoxinA, and
 incobotulinumtoxinA) for each week was calculated, as well as the average improvement in SAQ
 scores. Lower SAQ scores represented less severe patient reported disease. Percent
 improvement in SAQ score was calculated for each time point as the average post-treatment
 score divided by the average pre-treatment score for the treatment group, subtracted from 1.
 The SAQ scores for each time point and treatment groups were found to be normally distributed
 (passing both the D'Agostino & Pearson omnibus normality test as well as Shapiro-Wilk
 normality test) allowing for an assumption of Gaussian distribution in our following tests of
 statistical significance. Comparisons between treatments, and between time points within
 treatment groups were made with a one-way ANOVA followed by appropriate follow-up test for
 multiple comparisons. Comparisons within treatment groups between each follow-up time point,
 and the control pre-treatment time point were made using the Dunnett test (compares every
 mean to a control mean), whereas comparisons of different treatments at a given time point
 were made with the Tukey test (compares every mean to every other mean). A threshold of p ≤
 0.05 was used for statistical significance.

 Patients who had returned to their baseline SAQ score after a minimum of 12 weeks since their
 previous treatment were permitted to re-enroll in the study for subsequent treatments.
 Twenty-seven patients were studied, and 6 of these 27 were enrolled multiple times accounting
 for 11 of the 38 treatments studied. To ensure the baseline SAQ scores of these patients
 receiving repeat treatments did not differ from patients receiving a single treatment, the
 average pre-treatment SAQ score for patients undergoing repeat treatments was compared to the
 average pre-treatment SAQ score of single treatment patients for each type of botulinum toxin
 neuromodulator. These groups were evaluated for normality of distribution by the same method
 as described above, with single treatment patients passing tests of normality; normality for
 the repeat patients could not be determined due to the small number of treatments for each of
 these patients. Statistical comparisons were then made between the pre-treatment SAQ scores
 for repeat treatment patients and the respective (same type of botulinum toxin) single
 treatment patients. In order to preference type I error and identify any possible difference
 between these groups, we made an assumption of normality and used a one-way ANOVA followed by
 a Holm-Sidak multiple comparison test. The Holm-Sidak method was chosen as it has more power
 to identify significant differences than other possible methods such as that of Bonferroni.
Inclusion Criteria:

 -  Facial synkinesis

 Exclusion Criteria:

 -  Previous complication from botulinum toxin neuromodulator injection

 -  Inability to understand or complete the SAQ survey

 -  Inability to participate in follow-up

 -  Pregnancy