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.