Table 4.
Top five potential DDIs in the Lifelines cohort detected in the IADB.nl database with their kappa, sensitivity, specificity, PPV, and NPV, as well as 95% CI (time window: 3 months).
| CYP2D6/2C19/2C9 mediated potential DDI | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Potential DDI | Na | N1b | N2c | Detected in both databases (TP) | Over-reportingd (FP) |
Under-reportinge (FN) |
Kappa (95%CI) | Sensitivity, % (95%CI) |
Specificity, % (95%CI) |
PPV, % (95%CI) | NPV, % (95%CI) |
| CYP2D6 | |||||||||||
| metoprolol_paroxetine | 83 | 39 | 28 | 22 | 17 | 6 | 0.656 (0.655–0.656) | 78.57 (59.05–91.07) | 99.93 (99.89–99.96) | 56.41 (43.65–63.37) | 99.98 (99.95–99.99) |
| metoprolol_clomipramine | 18 | 15 | 11 | 10 | 5 | 1 | 0.769 (0.768–0.770) | 90.91 (58.72–99.77) | 99.98 (99.95–99.99) | 66.67 (44.94–83.05) | 100.00 (99.97–100.00) |
| metoprolol_fluoxetine | 17 | 10 | 9 | 9 | 1 | 0 | 0.947 0.946–0.947) | 100.00 (66.37–100.00) | 99.99 (99.98–100.00) | 90.00 (55.90–98.46) | 100.00 (-) |
| metoprolol_amiodarone | 14 | 11 | 5 | 5 | 6 | 0 | 0.625 (0.623–0.627) | 100.00 (47.82–100.00) | 99.98 (99.95–99.99) | 45.45 (27.24–64.97) | 100.00 (-) |
| metoprolol_duloxetine | 14 | 3 | 2 | 2 | 1 | 0 | 0.800 (0.797–0.802) | 100.00 (15.81–100.00) | 100.00 (99.98–100) | 66.67 (21.98–93.42) | 100.00 (-) |
| CYP2C19 | |||||||||||
| citalopram_omeprazole | 173 | 37 | 29 | 19 | 18 | 10 | 0.575 (0.574–0.576) | 65.52 (45.67–82.06) | 99.93 (99.89–99.96) | 51.35 (38.27–64.25) | 99.96 (99.93–99.98) |
| diazepam_omeprazole | 151 | 40 | 49 | 19 | 21 | 30 | 0.425 (0.424–0.426) | 38.78 (25.20–53.76) | 99.92 (99.87–99.95) | 47.50 (34.21–61.15) | 99.88 (99.85–99.91) |
| omeprazole_fluvoxamine | 28 | 5 | 4 | 3 | 2 | 1 | 0.667 (0.665–0.669) | 75.00 (19.41–99.37) | 99.99 (99.97–100.00) | 60.00 (25.13–87.02) | 100.00 (99.98–100.00) |
| diazepam_esomeprazole | 27 | 8 | 10 | 5 | 3 | 5 | 0.555 (0.553–0.557) | 50.00 (18.71–81.29) | 99.99 (99.97–100.00) | 62.50 (31.45–85.83) | 99.98 (99.96–99.99) |
| clopidogrel_omeprazole | 24 | 10 | 8 | 5 | 5 | 3 | 0.555 (0.553–0.557) | 62.50 (24.49–91.48) | 99.98 (99.95–99.99) | 50.00 (26.35–73.65) | 99.99 (99.97–100.00) |
| CYP2C9 | |||||||||||
| diclofenac_paroxetine | 51 | 9 | 14 | 4 | 5 | 10 | 0.347 (0.345–0.348) | 28.57 (8.39–58.10) | 99.98 (99.95–99.99) | 44.44 (19.32–72.77) | 99.96 (99.95–99.97) |
| ibuprofen_paroxetine | 22 | 4 | 6 | 1 | 3 | 5 | 0.200 (0.198–0.202) | 16.67 (0.42–64.12) | 99.99 (99.97–100.00) | 25.00 (3.86–73.47) | 99.98 (99.97–99.99) |
| naproxen_paroxetine | 20 | 6 | 4 | 3 | 3 | 1 | 0.600 (0.598–0.602) | 75.00 (19.41–99.37) | 99.99 (99.97–100.00) | 50.00 (22.01–77.99) | 100.00 (99.98–100.00) |
| diclofenac_fluoxetine | 14 | 4 | 3 | 1 | 3 | 2 | 0.286 (0.283–0.289) | 33.33 (0.84–90.57) | 99.99 (99.97–100.00) | 25.00 (4.48–70.29) | 99.99 (99.98–100.00) |
| diclofenac_fluvoxamine | 8 | 2 | 3 | 1 | 1 | 2 | 0.400 (0.397–0.403) | 33.33 (0.84–90.57) | 100.00 (99.98–100.00) | 50.00 (7.38–92.62) | 99.99 (99.98–100.00) |
aN, the number of participants with DDIs in the Lifelines cohort (n = 80,837); bN1, the number of participants with DDIs in the Lifelines cohort within overlapping population between the Lifelines and IADB.nl databases (n = 25,387); cN2, the number of participants with DDIs in the IADB.nl cohort within overlapping population between the Lifelines and IADB.nl databases (n = 25,387). dOver-reporting, detected only in the Lifelines cohort but not on the IADB.nl. eUnder-reporting, detected only in the IADB.nl but not in the Lifelines cohort.