NEW YORK (GenomeWeb) – A Veterans Health Administration subcommittee has recommended about half of the pharmacogenetic tests it evaluated to be more widely implemented across its facilities.
The Clinical Pharmacogenetics Subcommittee of the VHA's Molecular Diagnostics Working Group was charged with developing recommendations for standardizing pharmacogenetic testing across the VHA, which provides healthcare services for more than nine million veterans.
As the subcommittee reported today in Genetics in Medicine, it first developed consensus definitions for clinical validity and clinical utility and then weighed the evidence supporting the clinical utility of 30 drug-gene pairs. Only 13 percent of the pairs they examined were strongly recommended and 40 percent were recommended for greater use at VHA. For the remainder, the subcommittee said there was typically insufficient evidence of their clinical utility.
"Considered with other factors such as feasibility, cost, and patient and provider acceptance, these recommendations will inform national VHA policy for pharmacogenetic testing," wrote the Central Arkansas Veterans Healthcare System's Steven Schichman and his colleagues in their paper.
After defining clinical validity in this context to be the ability of a pharmacogenetic test to provide information about therapeutic efficacy or toxicity and clinical utility as the likelihood that the pharmacogenetic test information will lead to a clinical management change that will improve health outcomes, the researchers identified 30 drug-gene pairs to review.
All the pairs had Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations of Level A strength and all but two had a PharmGKB evidence level 1A, indicating strong clinical validity.
For these assessments, the subcommittee members, noted not only the indications for the drug's use, its mechanism of action, and its pharmacokinetics and pharmacogenetics, but also evidence from CPIC, PharmGKB, and other databases.
Based on this review, Schichman and his colleagues concluded that four of the tests should be strongly recommended before prescribing the associated drug, while 12 should be recommended, and 14 should not be routinely recommended.
Strongly recommended tests, the researchers noted, tended to identify severe adverse drug effects that could be avoided by giving another therapy, while tests that were not routinely recommended tended to inform drug efficacy but lacked evidence that their use improved outcomes.
For instance, Schichman and his colleagues highly recommended HLA-B*57:01 genotyping before abacavir use, as numerous studies have replicated the association between the genotype and a reaction to the drug and as a large clinical trial has found that prescreening could avoid hypersensitivity reactions. Additionally, other anti-retrovirals could be prescribed in its place, they said. They also noted the FDA label for abacavir includes a boxed warning that it not be prescribed for patients who test positive.
Similarly, they recommended CYP2D6 genotyping for codeine use, as it can guide providers to other dosage schemes or drugs. But they didn't strongly recommend it, as codeine is rarely prescribed alone or for the long term in the VHA population, they said.
However, they did not routinely recommend CYP2C19 genotyping prior to clopidogrel use. While they noted that genotyping could identify poor, normal, rapid, and ultra-rapid metabolizers, they said that similar information could be gleaned from platelet aggregometry and that no randomized trial has indicated that testing leads to lower cardiovascular event rates.
Schichman and his colleagues noted, though, that there could be some clinical scenarios in which not routinely recommended tests would be useful, and that their conclusions might not extend to other healthcare systems. They also pointed out that they did not evaluate the cost of testing.
They added, though, that they plan to continually update their recommendation as new evidence arises. "The Subcommittee's work highlights the need for additional rigorous outcomes research to promote the translation of pharmacogenetic discovery into patient care," the researchers wrote.