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.