2.2.3 Index for evaluation of remedial dosing strategies
Currently, there is no well-defined therapeutic range for edoxaban concentration. Therefore, the concept of “on-therapy range” was employed. It was built on the assumption that patients were at therapeutic goals when they reached full adherence. In our study, we defined the on-therapy range as between the 5thpercentile of trough and the 95th percentile of peak for both concentration and iFXa based on previous studies25-27 .
Non-adherence scenarios described previously were simulated for both PK and PD, and the percentages of individuals outside the on-therapy range were estimated. Moreover, the remedial strategies listed above were assessed for each non-adherence scenario. The total deviation time for each strategy was defined as the sum of the deviation time outside the on-therapy range of edoxaban concentration or iFXa and was calculated for each strategy.
The goal of the remedial strategy was to help patients minimise out-of-range duration. The strategy with the least total deviation time was considered optimal for each non-adherence scenario. Meanwhile, two remedial strategies were considered equivalent if the difference in the total deviation time was less than 1 h for the same non-adherence scenario.