PharmGKB response to the FDA Table for Pharmacogenetic Associations

In February, the FDA posted the Table for Pharmacogenetic Associations (PGx Table), and PharmGKB and CPIC blogged about the table a few days later.  We identified substantial areas of overlap and some differences between the gene-drug pairs listed on the FDA table and those with published CPIC guidelines. It is important to note that the FDA PGx Table, CPIC, and PharmGKB may update their content at any time. These comments reflect the PGx table as of May 2020,As of the current posting, the evidence the FDA used to construct the PGx Table is not explicitly posted, although most of the gene-drug pairs with therapeutic management recommendations on the PGx Table have labels also listed on FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling (Biomarker Table) containing some kind of prescribing information as defined by PharmGKB. The CPIC process for creating guidelines has been published and involves field experts conducting extensive reviews of the peer-reviewed literature, all of which is cited or listed as supporting evidence in the guideline publications.Direct comparison of which gene-drug pairs have CPIC guidelines versus which are listed on the FDA PGx Table is difficult due to the completely different manners in which the pairs are selected and ranked, as well as the different content and purposes of CPIC and the FDA PGx Table. Here we present our compilation tables of the gene-drug pairs on FDA’s PGx table with CPIC gene-drug pairs (some of which have guidelines, some are pending, and some are not considered actionable), PharmGKB annotations of drug labels found on FDA’s Biomarker Table, PharmGKB clinical annotations, and PharmGKB annotations of clinical guidelines published by several groups, including CPIC.  These tables are updated manually and therefore may not be current with recent changes in clinical guidelines, the FDA Biomarker Table or PharmGKB clinical annotations at the time of download.This blog post has also been submitted as a comment to the open docket at FDA.