2.2.4 Sensitivity analysis
Sensitivity analysis was applied to identify parameters that potentially impacted model outcome and their contribution to the overall variability. Sensitivity was assessed by the change in clearance (CL/F, 50-100%), CrCl (20-80 ml/min), and body weight (40–100 kg). The change in CL/F was assumed to reflect the impact of co-administration with a certain P-gp inhibitor (e.g. dronedarone, cyclosporine, and erythromycin), as concomitant use increased edoxaban exposure by 40% to 84.5% according to a previous study28. The detailed demographic and dosage information for sensitivity analysis are listed in supplementary Table 2.
Irregularly dosed intervals of 22–26 h (09:00, 07:00, and 09:00) and 26–22 h (09:00, 11:00, and 09:00) were tested considering that patients might take edoxaban at slightly different times every day. To ensure equivalence, the criterion used to evaluate the equality of different strategies was tested from 1–3 h. Sensitivity analysis was performed when the dose was delayed for 6, 12, 18, and 24 h.