Medicare will only cover genetic testing for individual response to the blood-thinner warfarin in the context of controlled clinical studies, effective immediately, CMS said Aug. 3.

Prior to the ¹ decision, there was no national policy on pharmacogenomic testing to predict warfarin response, nor were there any local coverage determinations on the topic.

The agency says there is not enough evidence to show that Medicare beneficiary health outcomes are improved by adjusting warfarin dosing based on assessment of mutations to the CYP2C9 or VKORC1 genes.

But data does suggest some link between the mutations and a patient's sensitivity to experiencing potentially fatal excessive bleeding in response to the drug. That is enough for a coverage-with-evidence-development policy, where beneficiaries enrolled in qualifying trials are covered.

Such a policy is appropriate "where additional data gathered in the context of clinical care would further clarify the impact of these items and services on the health of Medicare beneficiaries," CMS writes.

The final coverage decision is virtually identical to a proposal issued May 4 (² Also see "Genomic Tests For Warfarin Could Gain Coverage With Study Participation" - Medtech Insight, 11 May, 2009.).

The CED proposal was supported by the insurance industry and even by leading pharmacogenetic test developer Roche Diagnostics, which acknowledged the need for more evidence on warfarin testing. But Osmetech Molecular Diagnostics, one of several makers of FDA-approved tests for CYP2C9 and VKORC1 warfarin screening, pushed for broader coverage.

No Similar Prior Testing Permitted

Under the new policy, CMS will permit coverage for beneficiaries who have not been previously tested for CYP2C9 or VKORC1 alleles; have received fewer than five days of warfarin in the anticoagulation regimen for which the testing is ordered; and are enrolled in prospective, randomized, controlled clinical studies that meet specified standards.

A covered clinical trial must compare the frequency and severity of major and minor hemorrhaging, various thromboembolic events, and mortality in patients whose warfarin management includes genetic testing and in those who undergo a standard management program.

CMS also lists 13 basic standards that need to be met for a clinical study to qualify for coverage, such as registry on ClinicalTrials.gov and a protocol discussing how the results relate to the Medicare population specifically.

CMS Uses Framework Endorsed By MedCAC

In making its decision, CMS said it considered evidence from a framework developed by a government pilot project known as "Evaluation of Genomics Application in Practice and Prevention Initiative," or EGAPP, which a CMS advisory panel discussed in February (³ Also see "CDC Works To Track Evidence Gaps On Pharmacogenetic Tests" - Medtech Insight, 9 March, 2009.).

The Medicare Evidence Development and Coverage Advisory Committee's "strong endorsement has convinced us of [EGAPP's] importance," the agency writes. "CMS believes that the best current evidence on genetic testing for warfarin responsiveness does not rise to the highest level ('Level 1') of the EGAPP 2009 framework for clinical utility."

Used by more than a million people in the U.S. at any given time, warfarin - often sold under the brand name Coumadin - is indicated as an anticoagulant for patients with atrial fibrillation, venous thromboembolism, valvular heart disease, cerebrovascular disease and cardiac valve replacements.

In 2007, FDA updated the drug's labeling to include information on the usefulness of CYP2C9 and VKORC1 gene analysis; the language did not explicitly recommend such testing, though.

Since then, FDA has cleared a handful of genetic warfarin management assays, including Nanosphere's Verigene, AutoGenomics' INFINITI, ParagonDx' Rapid Genotyping Assay , Osmetech's eSensor and TrimGen's eQ-PCR . Many clinical laboratories offer home brew versions as well.

- Sue Darcey ( ⁴ s.darcey@elsevier.com )

CMS Will Cover Warfarin Gene Tests In Clinical Trials, But That's It

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