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Table 1. Key preparatory steps in establishing pharmacogenetic implementation programs
Preparatory steps Elements Points to consider
Selecting the The medications • Resources available include CPIC, FDA Table for Pharmacogenomic Associations,
medications, genes and DPWG Guidelines, FDA Tables of Pharmacogenetic Biomarkers, etc.
the laboratory • Clinically actionable examples can be found in many clinical specialties such
as cardiology, pain, psychiatry, infectious diseases, oncology, gastroenterology,
transplantation, neurology, and others
• Some high-risk PGx medications are backed by randomized controlled trials, e.g.,
Abacavir, carbamazepine, and mercaptopurine
• Some high-risk PGx medications have black box warnings highlighting their PGx
associations, e.g., warfarin and clopidogrel
The genes • Gene selection is mainly driven by medications in a reactive testing model
• Of note, the 24 CPIC guidelines cover 19 genes
• Most early adopters initiate their programs with the CYP genes, e.g., CYP2C19,
CYP2D6, and CYP2C9
• Other commonly implemented genes include VKORC1, SLCO1B1, and HLA-B
• Pre-emptive testing approach with a panel that covers common genes may reduce
the need to choose which gene(s) to test first
• Genes to be tested must have documented implications for medication response,
evidence of association with medication-related outcomes and pharmacogenetic-
guided therapeutic recommendation
• All relevant variants must be reviewed and interrogated during testing
The test and the lab • Laboratory must be CAP/CLIA accredited
• Test can be conducted in-house or with a commercia laboratory
• Commercial lab reports usually contains information on genes and variants tested,
genotypes, and phenotypes (pre-2019 reports may have included high-risk medications
and PGx-guided therapeutic recommendations)
Selecting the patients to The patients • Consider patients who have experienced adverse drug events or failed therapies in
test the past.
• Consider patients who are diagnosed with indications for which a PGx medication
treatment is anticipated.
• Consider patients who meet third party coverage determinations.
Providing oversight The • Success of this program is the responsibility of a multidisciplinary team
for implementation multidisciplinary • Pharmacists are leaders in this discipline and they play many key roles
program team • Other team members include physicians, geneticists, laboratory personnel,
informaticians, IT experts, nurses, patient advocates, institutional leadership, etc.
CPIC: Clinical Pharmacogenetics Implementation Consortium; FDA: United States Food and Drug Administration; DPWG: Dutch
Pharmacogenetics Working Group; PGx: pharmacogenetics; CYP: cytochrome P450; CAP/CLIA: College of American Pathologists/
Clinical Laboratory Improvement Amendments

classified as informative, actionable, and testing recommended or required. In February 2020, the FDA
published a table for pharmacogenomic associations which further delineates the type of pharmacogenetic
association as it relates to efficacy, adverse events, and pharmacokinetic associations . There are some
[10]
overlap between CPIC guidelines and the FDA’s table for pharmacogenomic associations; however several
differences have been noted as well. To date, there are 41 medications that have both CPIC guidelines
and FDA pharmacogenetic information. Of these 41 medications, the FDA drug-labels recommend
pharmacogenetic testing for four (i.e., oxcarbazepine, azathioprine, mercaptopurine, and thioguanine),
and requires testing for four more medications (i.e., abacavir, carbamazepine, ivacaftor, and rasburicase).
Specifically, abacavir, carbamazepine, and mercaptopurine are supported by randomized controlled trials
that documented improved clinical outcomes and cost effectiveness of pharmacogenetic testing before the
initiation of these medications [11-13] . The FDA has also updated some drug labels with black box warnings
for their pharmacogenetic associations such as clopidogrel, codeine, rasburicase, and pegloticase (https://
www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling) [Table 2].

The genes
Pharmacogenetic testing is the process of interrogating the implicated genes and variants to determine
one’s genotype and corresponding clinical phenotypes. The selection of the right gene(s) to test depends on
the medication(s) of interest. The two dozen CPIC guidelines published to date cover 19 genes. Most early
adopters of pharmacogenetics initiate their programs with the genes that encode the cytochrome P450 (CYP)