Table 4.
Comparison of models’ predictability in the low-, intermediate- and high-dose groups of the derivation cohort.
| Prediction model | IWPC-derived PGx algorithm | Lenzini and coworkers model | Clinically based algorithm† | Fixed-dose approach‡ | Puerto Rican algorithm |
|---|---|---|---|---|---|
| Low doses (≤3 mg/day) | |||||
| MAE (95% CI), mg/day | 1.22 (1.18–1.26) | 0.78 (0.62–0.94) | 1.54 (1.50–1.58) | 2.59 (2.53–2.65) | 0.70 (0.54–0.86) |
| R2 (%) | 20.1 | 34.2 | 49.0 | – | 48.4 |
| p-value† | NS | NS | 0.0162 | 0.0009 | – |
| Intermediate doses (>3 and <7 mg/day) | |||||
| MAE (95% CI), mg/day | 0.99 (0.94–1.04) | 1.18 (1.04–1.32) | 0.89 (0.83–0.95) | 0.88 (0.83–0.93) | 0.61 (0.52–0.70) |
| R2 (%) | 3.51 | 15.1 | 21.9 | – | 36.8 |
| p-value† | 0.0021 | 0.001 | 0.0001 | 0.0002 | – |
| High doses (≥7 mg/day) | |||||
| MAE (95% CI), mg/day | 3.74 (3.64–3.84) | 2.97 (2.28–3.66) | 6.11 (5.99–6.23) | 3.20 (3.11–3.29) | 2.35 (1.58–3.12) |
| R2 (%) | 1.76 | 6.8 | 0.34 | – | 4.17 |
| p-value§ | NS | NS | NS | NS | – |
Predicted warfarin daily doses (mg/day) with the Puerto Rican model, the Lenzini and coworkers pharmacogenetic refinement model [8], the IWPC pharmacogenetic-guided algorithm [2], and the clinical-based and fixed-dose approaches as compared with the actual doses of warfarin for the therapeutic effect in patients requiring low (≤3 mg/day) intermediate ( >3 and <7 mg/day), or high (≥7 mg/day) exposure. Data correspond to the study ‘derivation’ cohort of 163 Puerto Rican patients at the Veterans Affairs Caribbean Healthcare System-affiliated anticoagulation clinic. The 95% CIs of the estimates of MAEs were calculated. R2 is the coefficient of determination.
This algorithm is the same model developed in Puerto Ricans but excluding genotypes.
The fixed-dose was set as 5 mg of warfarin per day.
p-values for the comparison of proportions of ‘ideal dose’ estimates using the Puerto Rican pharmacogenetic algorithm versus the clinically based, Lenzini’s, IWPC-derived algorithms and the fixed-dose approach, as derived with the use of McNemar’s test of paired proportions.
IWPC: International Warfarin Pharmacogenomics Consortium; MAE: Mean absolute error; NS: Not significant differences (p ≥ 0.05); PGx: Pharmacogenomics.