Statistics
REGRESSION, ADVERSE EVENT, EVENT, ADVERSE EVENTS
Because participants in the LICON follow-up study were each enrolled immediately after completion of the ICON study (i.e. 48 weeks after ONS implantation), while the ICON study was still recruiting new patients until December 3rd 2017, the initial LICON participants (who started the ICON study already in 2013) had a much longer (potential) follow-up than those enrolled later (e.g. only in 2016). We therefore calculated the maximal potential follow durations for each individual participant and the entire group. First we calculated the potential maximal follow-up duration for each individual participant from the time they were included for the L-ICON follow-up study (i.e. immediately after they completed the ICON study 48 weeks after ONS implantation) to the end of the L-ICON follow-up study. Then, we calculated the total potential follow-up duration for the entire group by summing all individual potential follow-up durations and adding them together for all participants.Descriptive analyses were used to visualize response after ONS implantation. Furthermore, missing values for attack frequency and three SF36 items (mental health sum score, general health and physical health sum score) were imputed until 5 years after completion of the ICON trial (after the end of the open label extension, i.e. 48 weeks after implantation). Variations in the imputed datasets were analysed and pooled data from five different imputed datasets was used. Age, body mass index (BMI), sex, weekly attack frequency, mental health sum score, physical health sum score and general health score were used as predictors with predictive mean matching. Because of the low number of data points from 5 years after ICON trial completion, data was imputed until 5 years after completion of the ICON trial. The distribution of the attack frequencies was skewed. Therefore, we used the logarithm of the weekly attack frequency in the analyses and the geometric mean for the representation of the pooled data. Data is depicted with a 95% confidence interval (CI) around the pooled geometric or arithmetic mean. A Kaplan Meier survival analysis was performed for time to first treatment success, defined as ≥ 50% or ≥30% reduction in attack frequency. Participants were censored if the event had not occurred 5 years after ICON trial completion. A binary logistic regression model was used to predict a yes/no ≥ 50% reduction in attack frequency at 2 years after ICON trial completion. Sex, restlessness during attacks and ≥50% response in week 1–4, after implantation were used as categorical predictors. Age, mean weekly attack frequency at baseline and number of autonomic symptoms were used as continuous predictors. Adverse events and serious adverse events were depicted using a rate point estimate with a 95% confidence interval. As in the ICON study, serious adverse events were defined according to EN ISO 14155-1, which implies that surgical interventions and hospital admissions labelled as serious adverse events, irrespective of the nature of the hospital admission.