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Published on: January 16, 2019
Methodological issues in the development of a pharmacogenomic algorithm for warfarin dosing: comparison of two
Addepalli Pavani1, Shaik Mohammad Naushad, Addepally Uma
1Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, 500082, India.
Aim:
To ascertain whether multiple polynomial regression (MPR) has any advantage over multiple linear regression (MLR) in developing pharmacogenomic algorithms.
Materials & Methods:
Two pharmacogenomic algorithms were developed based on MPR and MLR models from a warfarin pharmacogenomic data set (derivation cohort [n = 125] and validation cohort [n = 115]).
Results:
The MPR model showed better correlation with therapeutic dose (r = 0.62 vs 0.52); better diagnostic utility in distinguishing the warfarin-sensitive and warfarin-resistant patients (area under the receiver operating characteristic curves: 0.89 vs 0.81); and lower rate of underestimation (13.9 vs 20%) compared with the MLR model. Rate of overestimation was higher in the MPR than the MLR (10 vs 6.7%) model.
Conclusion:
The MPR approach has advantages over the MLR approach in predicting accurate and safe dose.
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