Page 73 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

Withdrawal and botulinum toxin A: a double blind RCT
automatic imputation. In case of 14-27 completed days, the existing data were extrapolated to a 28-days period.
To assess long-term efficacy, we included the open label and follow-up phases in the analysis. As some placebo-treated patients received BTA in the open label phase, including these patients in the analysis of ‘placebo-treated patients’ would potentially confound the comparison. To avoid this, the open-label results (outcomes after 24, 36 and 48 weeks) of placebo-treated participants receiving open-label BTA were set to missing (see grey numbers in Figure 1). Thus, participants treated only with placebo were compared to participants who received one or two cycles of BTA. Participants providing at least one outcome measurement were included. We used Linear Mixed Models with changes from baseline to follow-up as the dependent variable. Such models automatically handle missing outcomes, including those censored by us. Fixed effects were treatment, visit number, treatment-by-visit number interaction, headache nurse, gender, depression, and anxiety. Covariates were age and baseline value of the variable of interest. Unstructured covariance matrices were used. We report the adjusted means with 95% confidence intervals. To facilitate objective assessment of the open-label longterm follow-up we present the results both as crude data, without any statistical modelling (Table 3), and by using the statistical model (Figure 4).
Two-sided p values <0.05 were considered statistically significant. Analyses were performed in SPSS23.0 (SPSS Inc., Chicago, USA). The audit trial of the trial register captures protocol amendments: no changes were made after unblinding of study investigators or completion of the trial. Data entry and processing was performed before unblinding of study investigators.
Role of the funding source
The study was funded by grants from the Netherlands Organization for Scientific Research and the Dutch Brain Foundation. They had no role in study design, data collection, data analysis, data interpretation, or writing of the report. JAP, DAK, EWZ and GMT had access to all data in the study and JAP, DAK, MDF, and GMT had final responsibility for the decision to submit for publication.
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