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.
- on our homepage by clicking "Clinically relevant PGx summaries'
- on gene, drug and variant pages under the 'Clinical PGx' tab
- made available as a download under the PharmGKB Data Usage Agreement
We describe these new level of evidence criteria in the new published article:
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.2012.96
Click here to download the PDF