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.