ArticlePharmacogenetics and genomics2009
Pharmacogenomic trial design: use of a PK/PD model to explore warfarin dosing interventions through clinical trial simulation.
Article in Pharmacogenetics and genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- The Creating an Optimal Warfarin Nomogram (CROWN) Study.Thrombosis and haemostasis · 2012Trial
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
objectiveVariants of two genes, CYP2C9 and VKORC1, explain approximately one third of variability in warfarin maintenance dose requirements. However, the clinical utility of using this information in addition to clinical and demographic data ('pharmacogenomic-guidance') is unclear, as few comparative clinical trials have been conducted to date. The objective of this study was to explore the incremental effect of pharmacogenomic-guided warfarin dosing under various conditions using clinical trial simulation.
methodsWe used an existing pharmacokinetic/pharmacodynamic model to perform clinical trial simulations of pharmacogenomic-guided versus standard of care warfarin therapy. The primary outcome was the percentage of patient time spent in therapeutic range over the first month of therapy. We assessed the influence of the frequency of INR monitoring, and the use of a loading dose and dose increase delay in patients with CYP2C9 variants.
resultsPharmacogenomic guidance resulted in a 3-4 percentage point absolute increase in time spent in therapeutic range over the first month of therapy compared with standard of care. The improvement in time in range was greater when the frequency of INR monitoring in both arms was assumed to be lower. The absolute difference increased to 6-8 percentage points with the use of a loading dose and dose increase delay in patients with a CYP2C9 variant.
conclusionOur initial results imply that pharmacogenomic-guided warfarin dosing may be more useful in settings with less intensive patient follow-up, and when adjustments are made for slower therapeutic response in patients with a CYP2C9 variant. Further pharmacokinetic/pharmacodynamic model development may be useful for warfarin pharmacogenomic trial design.
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Registered trials
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