A review of a priori regression models for warfarin maintenance dose prediction.

Bibliographic Details
Title: A review of a priori regression models for warfarin maintenance dose prediction.
Authors: Ben Francis, Steven Lane, Munir Pirmohamed, Andrea Jorgensen
Source: PLoS ONE, Vol 9, Iss 12, p e114896 (2014)
Publisher Information: Public Library of Science (PLoS), 2014.
Publication Year: 2014
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC4264860?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0114896
Access URL: https://doaj.org/article/3d1dd413ba044213b9e678da7e80fbc9
Accession Number: edsdoj.3d1dd413ba044213b9e678da7e80fbc9
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0114896
Published in:PLoS ONE
Language:English