PharmGKB Clinical Annotations Update and New Levels of Evidence

We have launched an update of our Clinical Annotations, assessing new evidence available for each gene variant - drug association. Each Clinical Annotation is written by a PharmGKB curator and assigned a level of evidence. We have recently revised our criteria to provide 6 levels of evidence, from the highest (1A) to the lowest (4), detailed below:

Level 1A - Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.  Level 1B - Annotation for a variant-drug combination where the preponderance of evidence shows an association.  The association must be replicated in more than one cohort with significant p-values, and preferably will have a strong effect size.Level 2A - Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.Level 2B - Annotation for a variant-drug combination with moderate evidence of an association.  The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.Level 3 - Annotation for a variant-drug combination based on a single significant (not yet replicated) association or annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association.Level 4 - Annotation based on a case report, non-significant study or in vitro, molecular or functional assay evidence only.

Clinical Annotations can be found on PharmGKB:

We describe these new level of evidence criteria in the new published article:Pharmacogenomics Knowledge for Personalized Medicine M Whirl-Carrillo, E M McDonagh, J M Hebert, L Gong, K Sangkuhl, C F Thorn, R B Altman and T E Klein. Clinical Pharmacology & Therapeutics (2012) 92: 414-417; doi:10.1038/clpt.2012.96Click here to download the PDF

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