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:
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
