TABLE 3.
Predictive performance of published pharmacokinetic models of tobramycin, including ME, MRE, and RMSE, and results of simulation-based npde diagnosticsa
| Model no. (reference) | Bias and imprecision |
npde diagnostics |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| ME (mg/liter)b | MRE (%)b | RMSE (%) | Mean | Variance | Skewness | Kurtosis |
P value |
|||
| Wilcoxon signed-rank test | Fisher test for variance | Shapiro-Wilks test | ||||||||
| Adult and pediatric patients | ||||||||||
| M1 (32) | 3.0 (2.5,3.5) | 75.3 (62.5, 88.2) | 131.1 | −0.3 | 1.5 | 0.5 | −0.1 | 0.0 | 0.0 | 0.0 |
| M2 (36) | 1.0 (0.5,1.4) | 19.2 (12.7, 25.7) | 57.6 | −0.1 | 0.7 | −0.1 | 1.2 | 0.2 | 0.0 | 0.0 |
| Pediatric patients | ||||||||||
| M3 (33) | 12.1 (11.4, 12.7) | 274.1 (240.4, 307.7) | 392.4 | −1.1 | 1.1 | −0.2 | −0.6 | 0.0 | 0.5 | 0.0 |
| M4 (32) | 2.4 (2.0, 2.9) | 71.5 (58.6, 84.4) | 129.1 | −0.3 | 1.6 | 0.4 | −0.3 | 0.0 | 0.0 | 0.0 |
| M5 (31) | 6.0 (5.3, 6.6) | 222.0 (187.2, 256.8) | 365.9 | −0.9 | 2.3 | 0.2 | −0.7 | 0.0 | 0.0 | 0.0 |
| M6 (11) | −0.4 (−0.7, 0.01) | 4.9 (−0.8, 10.6) | 47.8 | 0.0 | 0.8 | 0.0 | 1.6 | 0.5 | 0.0 | 0.0 |
| M7 (3) | 1.8 (1.4, 2.3) | 29.4 (22.2, 36.6) | 66.9 | −0.1 | 0.7 | −0.1 | 1.2 | 0.2 | 0.0 | 0.0 |
| M8 (41) | −4.0 (−4.6, −3.4) | −20.2 (−27.9, −12.5) | 67.4 | 0.2 | 2.7 | 0.0 | −1.3 | 0.0 | 0.0 | 0.0 |
a
Presented are summary statistics for the distribution of the npde’s: mean, variance, skewness, and kurtosis. The expected value of these four variables for N(0, 1) are, respectively, 0, 1, 0, and 0. Further results for (i) a Wilcoxon signed-rank test, to test whether the mean is significantly different from 0, (ii) a Fisher test for variance, to test whether the variance is significantly different from 1, and (iii) a Shapiro-Wilks test, to test whether the distribution is significantly different from a normal distribution, are presented (30).
b
Data in parentheses are 95% confidence intervals.