Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Pharmacogenomics. 2012 Aug;13(11):1239-45. doi: 10.2217/pgs.12.101.
To evaluate the performance of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) acenocoumarol dose algorithms in an independent data set. The EU-PACT trial investigates the added value of pretreatment genotyping for use of warfarin, phenprocoumon and acenocoumarol.
PATIENTS & METHODS: External validation was performed in the Rotterdam Study cohort using information about 707 acenocoumarol users. R(2), which measures the strength of correlation between the predicted and observed acenocoumarol dose, mean absolute error and mean squared error were calculated to evaluate the performance of the original algorithm.
Validation resulted in a R(2) of 52.7 and 12.9% compared with an R(2) of 52.6 and 17.8% in the original study for the genotype-guided and nongenotype-guided dose algorithm, respectively. For the genotype-guided dose algorithm, the mean absolute error was 0.48 mg/day and the mean squared error was 0.38 (mg/day)(2). For the nongenotype-guided dose algorithm, the mean absolute error was 0.62 mg/day and the mean squared error was 0.63 (mg/day)(2).
The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.
评估欧洲抗凝治疗药物基因组学（EU-PACT）依诺肝素剂量算法在独立数据集的性能。EU-PACT 试验研究了预处理基因分型对使用华法林、苯丙香豆素和依诺肝素的附加价值。
在鹿特丹研究队列中进行了外部验证，该队列使用了 707 名依诺肝素使用者的信息。计算 R²（衡量预测和观察到的依诺肝素剂量之间的相关性强度）、平均绝对误差和平均平方误差，以评估原始算法的性能。
验证结果显示，基因型指导剂量算法的 R²为 52.7%和 12.9%，与原始研究中的 R²为 52.6%和 17.8%相比有所下降。对于基因型指导剂量算法，平均绝对误差为 0.48mg/天，平均平方误差为 0.38（mg/天）²。对于非基因型指导剂量算法，平均绝对误差为 0.62mg/天，平均平方误差为 0.63（mg/天）²。
EU-PACT 依诺肝素算法在本研究中的性能与原始研究相同，这意味着它适用于各种人群。
