Frequency of analyses

A DMEC (made up of at least two clinicians and one statistician that are independent of the study team) will be set up to review data on safety, activity, protocol adherence and recruitment. The DMEC will review safety data for all participants entered into the trial after 12 participants have been recruited, and 3-monthly thereafter. Interim reports containing safety data, protocol adherence and recruitment will be presented to the DMEC in strict confidence at, at least, yearly intervals. This committee, in light of the interim data, and any advice and evidence they wish to request, will if necessary report to the TSC if there are any concerns regarding the activity or safety of the trial treatments.

The DMEC may also report to the TSC, with a recommendation of early release of data, should ICD be found to be significantly superior to CD during the interim analysis (once 70% of PFS events have been observed).

Final analysis will take place in two stages. Analysis of the primary endpoint will take place when at least 198 PFS events have been observed. At this time, all other endpoints relating to the first ‘phase’ of the study, with the exception of OS, will be analysed. A decision will be made based on the overall number of deaths observed as to whether OS will be analysed at the same time as PFS, or whether additional follow-up is required prior to analysis. Analyses relating to the switch phase of the study will take place after a minimum of 6 months follow-up after the last CD participant to switch treatments has started ICD treatment.