Comparison of targeted vs. expanded pharmacogenomic testing: What are we missing?

BACKGROUND: Pharmacogenomics (PGx) is used as a medication management strategy by a small but growing number of institutions. PGx allows prescribers to individually treat patients concordant with their genes. Recent litigation for preventable PGx-mediated adverse events highlights the need to accelerate PGx implementation for patient safety. Genetic variations cause drug metabolism, transport, and target changes, affecting medication response and tolerability. PGx testing often consists of targeted testing aimed at specific gene-drug pairs or disease states. Conversely, expanded panel testing can evaluate all known actionable gene-drug interactions, enhancing proactive clarity regarding patient response. OBJECTIVES: Evaluate the divergence of targeted PGx testing with a single gene-drug pair test (cardiac), a two-gene panel, and a focused psychiatric panel compared to expanded PGx testing. METHODS: An expanded PGx panel (≥25 genes) was compared to a single gene-drug pair test of CYP2C19/clopidogrel, a dual gene test of CYP2C19/CYP2D6, a 7-gene psychiatric list, and a 14-gene psychiatric panel to inform specific depression and pain management drugs. The expanded panel provided a baseline to evaluate total PGx variations compared to those possibly missed by targeted testing. RESULTS: Targeted testing did not identify up to 95% of total PGx gene-drug interactions discovered. The expanded panel reported all gene-drug interactions for any medication with Clinical Pharmacogenomics Implementation Consortium (CPIC) guidance or U.S. Food and Drug Administration (FDA) labeling for that gene. Single gene CYP2C19/clopidogrel testing missed or did not report on ∼95% of total interactions, CYP2C19/CYP2D6 testing missed or did not report ∼89%, and the 14-gene panel missed or did not report on ∼73%. The 7-gene list missed ∼20% of discovered potential PGx interactions but was not designed to identify gene-drug interactions. CONCLUSIONS: Targeted PGx testing for limited genes or by specialty may miss or not report significant portions of PGx gene-drug interactions. This can lead to potential patient harm from the missed interactions and subsequent failed therapies and/or adverse reactions.