Table 2.
Final Model Population Parameter Estimates
| Parameter | Typical Value (95% CI*) | Variability (95% CI*) |
|---|---|---|
| Baseline cfu for drug sensitive, log10cfu | 5.75 (5.19 to 6.09) | 0.892† (0.543 to 1.20) |
| Baseline cfu for inhA, 5 mg/kg, log10cfu | 5.87 (5.18 to 6.36) | — |
| Baseline cfu for inhA, 10–15 mg/kg, log10cfu | 6.63 (6.27 to 7.01) | — |
| Additive error in cfu, log10cfu | 0.493 (0.42 to 0.565) | — |
| Growth rate in MGIT drug sensitive, kgrowth, 1/d | 1.65 (1.45 to 1.97) | — |
| Growth rate in MGIT for inhA, kgrowth, 1/d | 1.19 (1.04 to 1.42) | — |
| Delay of growth in MGIT after INH treatment, h | 5.85 (0.971 to 11.2) | 14.2‡ (10.4 to 17.3) |
| MGIT detection threshold, log10cfu | 9.31 (8.93 to 9.78) | — |
| Proportional error in TTP, % | 13.3 (11.1 to 14.9) | — |
| EC50 for drug sensitive, mg/L | 0.01 fixed | — |
| EC50 for inhA, mg/L | 0.544 (0.125 to 3.22) | — |
| Gamma, ϒ (·) | 2.88 (1.04 to 7.93) | — |
| Killmax, 1/d | 0.42 (0.355 to 0.907) | 62.0§ (52.0 to 66.0) |
| T1/2E0, half-life of effect compartment delay, h | 17.0 (3.94 to 31.3) | — |
| Correlation of the cfu–TTP errors, % | −36.7 (−52.5 to −22.4) | — |
Definition of abbreviations: cfu = colony-forming units; CI = confidence interval; EC50 = 50% concentration at which 50% of the maximum induced kill by isoniazid is achieved; INH = isoniazid; MGIT = Mycobacterial Growth Indicator Tubes; TTP = time to positivity.
The ε-shrinkage for cfu = 8% and TTP = 17%.
Coefficient of variation was calculated by , where ω2 represent the variance.
Estimated from nonparametric bootstrap of the final model (n = 200, stratified on arm).
The between-subject variability of the parameter estimate expressed as SD (in the log10 scale).
The between-occasion variability of the parameter expressed as approximate coefficient of variation (CV%).
The between-subject variability of the parameter expressed as approximate coefficient of variation (CV%).