TABLE 4.
Prophylaxis study model parameter comparison using the original data set, the external data set (PPRU study data), and the merged data set
| Parameter | Parameter value (% RSE) from prophylaxis study modela |
Results of bootstrap analysis (n = 1,000)b with PPRU study data (external data set) fitted using prophylaxis study model |
Results of bootstrap analysis (n = 1,000)c with merged data set fitted using prophylaxis study model |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Prophylaxis study data fitting (internal data set) | PPRU study data fitting (external data set) | Merged data set fitting | 2.50% | 50% | 97.50% | 2.50% | 50% | 97.50% | |
| Fixed effects | |||||||||
| V (liters/kg) | 1.00 (4) | 1.00 (5) | 1.01 (3) | 0.913 | 1.0 | 1.10 | 0.952 | 1.01 | 1.06 |
| CL (liter/h/kg0.75) | 0.013 (3) | 0.012 (10) | 0.012 (3) | 0.009 | 0.011 | 0.013 | 0.011 | 0.012 | 0.013 |
| Exponent for SCR as a covariate on CL | −0.410 (12) | −0.160 (34) | −0.262 (15) | −0.291 | −0.168 | −0.075 | −0.348 | −0.262 | −0.189 |
| Exponent for PMA as a covariate on CL | 2.05 (17) | 1.64 (20) | 1.88 (12) | 0.757 | 1.66 | 2.22 | 1.39 | 1.89 | 2.29 |
| Ka (1/h) | 0.961 (26) | —d | 1.00 (fixede) | — | — | — | — | — | — |
| F1 | 0.995 (7) | — | 1.00 (fixed) | — | — | — | — | — | — |
| IIV | |||||||||
| ω2 (V) | 0.017 (61) | 0.064 (33) | 0.032 (32) | 0.019 | 0.062 | 0.115 | 0.010 | 0.030 | 0.052 |
| ω2 (CL) | 0.051 (29) | 0.140 (26) | 0.082 (18) | 0.072 | 0.133 | 0.242 | 0.054 | 0.081 | 0.113 |
| Covariance (CL − V) | −0.021 (58) | 0.010 (282) | 0.002 (589) | −0.052 | 0.007 | 0.056 | −0.024 | 0.002 | 0.025 |
| Residual errorf | |||||||||
| σ2 (Prop) | 0.214 (12) | 0.207 (24) | 0.224 (9) | 0.061 | 0.201 | 0.275 | 0.178 | 0.223 | 0.263 |
| σ2 (Add) (mg/ml) | 0.505 (36) | 0.266 (64) | 0.356 (34) | 0.002 | 0.064 | 0.267 | 0.012 | 0.121 | 0.328 |
CL (in liters per hour) = 0.0127 · (WT/1)0.75 · (SCR/0.8)−0.41 · (PMA/28)2.05, V (in liters) = 1.00 × (WT/1), Ka (in 1/hour) = 0.96, F1 = 100%, where CL is clearance, WT is actual body weight (in kilograms), SCR is the serum creatinine concentration (in milligrams per deciliter), PMA is postmenstrual age (PMA; in weeks), V is the volume of the central compartment; Ka is the absorption rate constant, F1 is the oral bioavailability, IIV is the interindividual variability, ω2 is the variance of the IIV term, σ2 is the variance of the residual error term, RSE is the residual standard error, and PPRU is the Pediatric Pharmacology Research Unit.
A total of 995 (99.5%) runs successfully minimized the covariance step and 1,000 (100%) runs completed the covariance step.
A total of 1,000 (100%) runs successfully minimized the covariance step and 1,000 (100%) runs completed the covariance step.
—, estimated parameter value not applicable.
Fixed, the parameter was fixed to the original estimate from prophylaxis model in order for the covariance step to run.
Residual error model: W = SQRT(THETAerror2) and Y = IPRED + ERR(1) × W × IPRED + ERR(2), where W is the proportional residual error term, SQRT is square root, THETAerror is the theta estimate of the proportional residual error, Y is a composite expression for model-predicted concentrations, IPRED is the individual predicted concentration, ERR(1) is fixed at 1.00, ERR(2) is the additive residual error, Prop is the proportional error term, and Add is the additive error term.