Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study

Rianne M F van Schie; Nadia el Khedr; Talitha I Verhoef; Martina Teichert; Bruno H Stricker; Albert Hofman; Peter N Buhre; Judith A M Wessels; Tom Schalekamp; Saskia le Cessie; Felix J M van der Meer; Frits R Rosendaal; Anthonius de Boer; Anke-Hilse Maitland-van der Zee; Loes E Visser

doi:10.2217/pgs.12.101

Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study

Rianne M F van Schie, Nadia el Khedr, Talitha I Verhoef, Martina Teichert, Bruno H Stricker, Albert Hofman, Peter N Buhre, Judith A M Wessels, Tom Schalekamp, Saskia le Cessie, Felix J M van der Meer, Frits R Rosendaal, Anthonius de Boer, Anke-Hilse Maitland-van der Zee, Loes E Visser

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

AIM: 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.

RESULTS: 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).

CONCLUSION: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.

Original language	English
Pages (from-to)	1239-45
Number of pages	7
Journal	Pharmacogenomics
Volume	13
Issue number	11
DOIs	https://doi.org/10.2217/pgs.12.101
Publication status	Published - Aug 2012

Keywords

Acenocoumarol
Aged
Aged, 80 and over
Algorithms
Anticoagulants
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP2C9
Dose-Response Relationship, Drug
Female
Genotype
Humans
Individualized Medicine
International Normalized Ratio
Male
Middle Aged
Mixed Function Oxygenases
Pharmacogenetics
Phenprocoumon
Polymorphism, Single Nucleotide
Vitamin K Epoxide Reductases
Warfarin

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van Schie, R. M. F., el Khedr, N., Verhoef, T. I., Teichert, M., Stricker, B. H., Hofman, A., Buhre, P. N., Wessels, J. A. M., Schalekamp, T., le Cessie, S., van der Meer, F. J. M., Rosendaal, F. R., de Boer, A., Maitland-van der Zee, A.-H., & Visser, L. E. (2012). Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study. Pharmacogenomics, 13(11), 1239-45. https://doi.org/10.2217/pgs.12.101

@article{f7e93f2a4a294a74b276f3455474881d,

title = "Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study",

abstract = "AIM: 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.RESULTS: 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).CONCLUSION: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.",

keywords = "Acenocoumarol, Aged, Aged, 80 and over, Algorithms, Anticoagulants, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2C9, Dose-Response Relationship, Drug, Female, Genotype, Humans, Individualized Medicine, International Normalized Ratio, Male, Middle Aged, Mixed Function Oxygenases, Pharmacogenetics, Phenprocoumon, Polymorphism, Single Nucleotide, Vitamin K Epoxide Reductases, Warfarin",

author = "{van Schie}, {Rianne M F} and {el Khedr}, Nadia and Verhoef, {Talitha I} and Martina Teichert and Stricker, {Bruno H} and Albert Hofman and Buhre, {Peter N} and Wessels, {Judith A M} and Tom Schalekamp and {le Cessie}, Saskia and {van der Meer}, {Felix J M} and Rosendaal, {Frits R} and {de Boer}, Anthonius and {Maitland-van der Zee}, Anke-Hilse and Visser, {Loes E}",

year = "2012",

month = aug,

doi = "10.2217/pgs.12.101",

language = "English",

volume = "13",

pages = "1239--45",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Future Medicine Ltd.",

number = "11",

}

van Schie, RMF, el Khedr, N, Verhoef, TI, Teichert, M, Stricker, BH, Hofman, A, Buhre, PN, Wessels, JAM, Schalekamp, T, le Cessie, S, van der Meer, FJM, Rosendaal, FR, de Boer, A, Maitland-van der Zee, A-H & Visser, LE 2012, 'Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study', Pharmacogenomics, vol. 13, no. 11, pp. 1239-45. https://doi.org/10.2217/pgs.12.101

TY - JOUR

T1 - Validation of the acenocoumarol EU-PACT algorithms

T2 - similar performance in the Rotterdam Study cohort as in the original study

AU - van Schie, Rianne M F

AU - el Khedr, Nadia

AU - Verhoef, Talitha I

AU - Teichert, Martina

AU - Stricker, Bruno H

AU - Hofman, Albert

AU - Buhre, Peter N

AU - Wessels, Judith A M

AU - Schalekamp, Tom

AU - le Cessie, Saskia

AU - van der Meer, Felix J M

AU - Rosendaal, Frits R

AU - de Boer, Anthonius

AU - Maitland-van der Zee, Anke-Hilse

AU - Visser, Loes E

PY - 2012/8

Y1 - 2012/8

N2 - AIM: 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.RESULTS: 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).CONCLUSION: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.

AB - AIM: 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.RESULTS: 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).CONCLUSION: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.

KW - Acenocoumarol

KW - Aged

KW - Aged, 80 and over

KW - Algorithms

KW - Anticoagulants

KW - Aryl Hydrocarbon Hydroxylases

KW - Cytochrome P-450 CYP2C9

KW - Dose-Response Relationship, Drug

KW - Female

KW - Genotype

KW - Humans

KW - Individualized Medicine

KW - International Normalized Ratio

KW - Male

KW - Middle Aged

KW - Mixed Function Oxygenases

KW - Pharmacogenetics

KW - Phenprocoumon

KW - Polymorphism, Single Nucleotide

KW - Vitamin K Epoxide Reductases

KW - Warfarin

U2 - 10.2217/pgs.12.101

DO - 10.2217/pgs.12.101

M3 - Article

C2 - 22920394

SN - 1462-2416

VL - 13

SP - 1239

EP - 1245

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 11

ER -

Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study

Abstract

Keywords

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