Table I.
Models Used for Numerical Experiments
| Model | Reference | Model classification | Fixed effects | Random effects | Residual error | Number of subjects | Number of samples | Comment |
|---|---|---|---|---|---|---|---|---|
| A | Jönsson et al. (18) | Two-comp. PK | 7 | 2 | Additive | 177 | 1196 | Closed form |
| B | Bergmann et al. (19) | Two-comp. PK | 10 | 3 | Additive and proportional | 93 | 274 | Closed form |
| C | Wählby et al. (20) | Two-comp. PK, transit comp. power PD | 7 | 4 | Additive and proportional | 47 | 530 | ODEs |
| D | Grasela and Donn (21) | One-comp. PK, | 3 | 3 | Proportional | 59 | 155 | Closed form |
| E | Practically non-identifiable Emax model. | 8 | 5 | Additive and proportional | 326 | 1803 | ED50 and γ cannot both be estimated on sim. Data | |
| F | Non-identifiable example from Aoki et al. (22) | Structurally non-identifiable two-comp. PK w/ fraction of dose data | 4 | 3 | Proportional | 25 | 612 | V1, Q, V2, and CL cannot all be estimated |
Comp., compartment; DEs, differential equations; γ, hill factor for Emax model; ED50, dose required for half effect; V1, volume of central compartment; V2, volume of peripheral compartment; Q, intercompartmental clearance; CL, clearance