Covariate analysis
Age, height, LBW, FFM, BMI and centre of inclusion were explored as covariates. In univariate analysis - using the structural model without application of allometric scaling – the separately weight-related covariates body weight, FFM and LBW were significantly related to CL and V1. We chose however to allometrically scale these parameters with body weight as it is easy and routinely measured, as opposed to LBW and FFM. Incorporation of a separate residual error for one haemophilia treatment centre improved the model (p<0.05), but was not significant after the backward selection reprocess (p<0.01). Therefore, all centres were described by the same residual error model. CL decreased with age; the latter was the only covariate that improved the fit of the model to the data. On basis of this relationship typical clearance of a 73 kg patient would decrease from 1.89 dL/h at an age of 20 years to 1.36 dL/h at an age of 70 years.