Individual dosing advice
To evaluate the clinical impact of the choice of model on dosing
regimens, we compared the dose (IU) for each individual with a PK
profile assessment of rFIX-Fc (n=36) as calculated by application of
Bayesian forecasting using both the published and the developed novel
model. Individual PK parameters were calculated for the clinical
situation in which a peak, trough and random mid FIX activity level were
available. Doses were targeted at maintaining a FIX level
>3 IU/dL at 168h after infusion of rFIX-Fc during
steady-state (Dose3%). We wanted to perform Bayesian
forecasting on data that was not included in the development of the
model. Hence, five separate datasets including 29-30 patients were
created on which population PK parameters were estimated. These
estimates were used for Bayesian forecasting using three individual
samples of the remaining 6-7 patients not included in the dataset.
Differences in calculated doses between the two models were explored by
the permutation test, as the doses were not normally distributed and
contained too many ties to perform a Wilcoxon signed rank test. This
analysis was also performed separately for children <12 years
of age, since the previously published model did not include children
<12 years of age, whereas the newly developed model did.