Table 3.
Shortening metric values calculated (with 95% confidence intervals indicated) for evaluation of the assay’s predictivity of QT shortening in the rabbit ventricular wedge experiments when considering the different uses of the available ion channel data described. Entries are ordered alphabetically by the data type used in the simulations. The missing entry is due to the inability to calculate the metric due to there being no compounds in the relevant categories for its computation.
| Case number | Ion channel data use combination | Accuracy (%) |
Kappa value |
Sensitivity (%) |
Specificity (%) |
Positive predictive value (%) |
Negative predictive value (%) |
|---|---|---|---|---|---|---|---|
| 1 | IonWorks/FLIPR data, multiple channel block, fitting for IC50 value (121 compounds) | 69.4 (60.7–76.9) |
0.13 (−0.10–0.37) |
29.0 (16.1–46.6) |
83.3 (74.3–89.6) |
37.5 (24.7–52.3) |
77.3 (68.0–84.5) |
| 2 | IonWorks/FLIPR data, multiple channel block, fitting for IC50 value & Hill coefficient (121 compounds) | 71.1 (62.4–78.4) |
0.23 (0.02–0.45) |
41.9 (26.4–59.2) |
81.1 (71.8–87.9) |
43.3 (30.0–57.8) |
80.2 (70.9–87.1) |
| 3 | IonWorks/FLIPR data, multiple channel block including KCNQ1 interactions, fitting for IC50 value (121 compounds) | 69.4 (60.7–76.9) |
0.13 (−0.10–0.37) |
29.0 (16.1–46.6) |
83.3 (74.3–89.6) |
37.5 (25.0–51.9) |
77.3 (68.0–84.5) |
| 4 | PatchXpress data, hERG block only, fitting for IC50 value (77 compounds) | 76.6 (66.0–84.7) |
0.00 (−0.40–0.40) |
0.00 (0.00–17.6) |
100 (93.9–100) |
– | 76.6 (66.0–84.7) |
| 5 | PatchXpress data, multiple channel block, fitting for IC50 value (77 compounds) | 76.6 (66.0–84.7) |
0.26 (−0.04–0.56) |
33.3 (16.3–56.3) |
89.8 (79.5–95.3) |
50.0 (31.8–68.2) |
81.5 (70.4–89.1) |
| 6 | PatchXpress data, multiple channel block, fitting for IC50 value & Hill coefficient (77 compounds) | 75.3 (64.6–83.6) |
0.24 (−0.06–0.54) |
33.3 (16.3–56.3) |
88.1 (77.5–94.1) |
46.2 (29.3–63.9) |
81.3 (70.0–88.9) |
| 7 | PatchXpress data, multiple channel block, fitting for IC50 value, one-dimensional simulation (77 compounds) | 72.7 (61.9–81.4) |
0.22 (−0.06–0.51) |
38.9 (20.3–61.4) |
83.1 (71.5–90.5) |
41.2 (26.5–57.6) |
81.7 (70.1–89.4) |
| 8 | QSAR data, multiple channel block (372 compounds) | 79.8 (75.5–83.6) |
0.10 (−0.09–0.28) |
14.1 (7.58–24.6) |
93.5 (90.2–95.8) |
31.0 (26.1–36.5) |
84.0 (79.7–87.5) |