Leading PGx Resources Show Incongruous Gene-Drug Interactions, Dosing Recommendations

Leading PGx Resources Show Incongruous Gene-Drug Interactions, Dosing Recommendations
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Only five of the 126 drugs that were listed by both the FDA’s Table of Pharmacogenetic Associations and those listed by the Clinical Pharmacogenetics Implementation Consortium (CPIC) showed the same drug-gene associations and dosing implications. The differences point to one reason why pharmacogenomics (PGx) lags in adoption by physicians.

“This study reveals conflicting information regarding potential drug-gene interactions that undoubtedly cause confusion among health care providers, thereby slowing the integration of pharmacogenomics, one of the pillars of personalized medicine, into clinical care,” said Personalized Medicine Coalition (PMC) President Edward Abrahams.

The comparative analysis, led by PMC researchers, was published yesterday in the American Journal-Health Pharmacy and showed additional deviations among the two most common pharmacogenomic clinical guidelines. Thirty-four drugs were listed by both sources, but showing differing gene-drug interactions and dosing recommendations, while 87 drugs were listed by only one of the two sources.

According to the study authors—which included PMC Senior Vice President for Science Policy Daryl Pritchard, Ph.D.; Atrium Health Cancer Pharmacology and Pharmacogenomics Chair Jai N. Patel, Pharm.D.; PMC Program Manager Lindsay E. Stephens; and Intermountain Healthcare Executive Clinical Director of Precision Health Howard L. McLeod, Pharm.D.—a clear understanding of information about gene-drug interactions is needed in order for clinicians to make optimal use of PGx testing for their patients.

One potential reason for the differences in the two sources, the authors noted, “may be due in part to FDA having access to PGx information that is unavailable in published literature and/or because PGx classifications are based on criteria other than clinical actionability.”

The discordance among different PGx sources is a known problem among policy makers and PGx experts, who have advocated for improved collaboration between FDA, CPIC, clinical guideline developers, and other stakeholders. “A collaborative approach will minimize duplicative efforts and harmonize solutions for an immediate impact on public health,” the study authors noted.

One such collaborative effort is a new pharmacogenomics collaborative PGx organization called the Standardizing Laboratory Practices in Pharmacogenomics (STRIPE). STRIPE’s goal is to convene diverse stakeholders to address challenges and opportunities for PGx testing and includes the development of the Pharmacogenomic Clinical Annotation Tool (PharmCAT)—a collaborative effort of The Pharmacogenomics Knowledge Base (PharmGKB) and the former PGRN Statistical Analysis Resource, as well as other groups. The intent of PharmCAT is to extract guideline variants from a genetic dataset, interpret the variant alleles, and make prescribing recommendations that can be used to inform treatment decisions.

Aside from the incongruities between the PGx sources, the researchers also note that most practitioners, aside from those implementing PGx, aren’t aware of the CPIC guidelines and also don’t use the PGx information included in the labeling of many approved drugs.

“There should be a concerted effort from professional medical organizations to evaluate PGx information using sources from CPIC, PharmGKB, and FDA to inform clinical practice recommendations,” the authors conclude.