Evidence proving a genetic test’s clinical utility — the elusive “so-what factor” — influences reimbursement decisions to such an extent that even a nod from the US Food and Drug Administration sometimes isn’t enough to swing the pendulum in a product’s favor, according to an Aetna official.
When determining reimbursement for gene-based tests, Aetna, the third-largest health insurer in the US, holds diagnostics companies to the same evidence requirements for establishing appropriate analytical validity, clinical validity, and clinical utility as they do the makers of other types of medical products.
“For personalized medicine and genetic technologies, the standards are the same as the standards that are used for all other areas of medicine,” Joanne Armstrong, regional medical director of women’s health at Aetna, said during the Drug Information Association’s annual meeting, held last week in Atlanta.
Aetna, which covers nearly 15 million Americans, considers as part of its reimbursement metrics data in peer-reviewed publications, decisions of regulatory bodies, and measures of analytic validity, clinical validity, and clinical utility. The insurer also assesses whether a product affects a policy holder’s course of treatment, improves outcomes, and has applicability in a broader population outside of an investigational setting.
The insurer is most concerned with measures of clinical utility, or “the so what factor,” Armstrong said. “When you use it how does it change healthcare decision making and healthcare outcomes.” She noted that peer-reviewed published studies showing clinical utility is one area where diagnostics are most lacking.
According to Armstrong, Roche Diagnostics’ FDA-approved AmpliChip is one example of a product that hasn’t met Aetna’s evidence requirements for reimbursement.
Although the test may be FDA approved, Aetna notes in its policy that Roche should perform controlled clinical trials to prove that the test will reduce adverse drug reactions. Aetna also has asked that Roche compare the AmpliChip, which interrogates CYP2D6 and CYP2C19 polymorphisms, with standard therapeutic drug-monitoring techniques.
Roche officials have spoken out against insurance companies holding genetic tests to the same evidence standards as drugs and other medical products [see PGx Reporter 04-25-2007].
At the DIA meeting, Klaus Lindpaintner, vice president and director of Roche Genetics, said that while the company has ongoing studies that would address some of the evidence requirements requested by insurance companies, these types of tests are a significant time and monetary investment. Roche would not provide more detail on these ongoing studies.
In developing its reimbursement policies, Aetna also looks at other payors, particularly the Centers for Medicare and Medicaid services. Aetna’s genetic technology policy falls in line with CMS’ view that is not necessary to devise a special system for ensuring the utility and validity of genetic tests [see PGx Reporter 06-13-2007].
At the DIA meeting, Lawrence Lesko, director of the FDA’s Office of Clinical Pharmacology & Biopharmaceutics, seemed to take issue with Aetna’s reimbursement policies for diagnostic tests.
“One of the things that strikes me in a lot of the sessions that I sit in on … [is] that we find more reasons not to proceed with personalized medicine than to proceed with it and find reasons to go forward,” he said.
He noted that AmpliChip may be clinically useful in predicting which patients will benefit from breast cancer treatment with tamoxifen. Last year, an FDA advisory panel recommended that the agency should update tamoxifen’s label to include information about CYP2D6 genotype testing [see PGx Reporter 11-15-2006].
Special Treatment for Ailing Diagnostics
A 1997 NIH report called “Promoting Safe and Effective Genetic Testing in the United States”urged the Centers for Disease Control and Prevention to create a specialty for genetic tests to ensure their quality and to “facilitate assigning separate billing and reimbursement codes for each use of a genetic test.”
Although the absence of reimbursement codes for genetic tests is often cited as a major barrier to garnering coverage, patient groups, industry, and regulatory agencies all disagree whether genetic technologies need to be reviewed under special rules and regulations. While patient groups like the Genetics & Public Policy Center and the Genetic Alliance have urged CMS to create a genetic specialty under the Clinical Laboratories Improvement Amendments, CMS has said that existing CLIA regs are sufficient to ensure the safety and effectiveness of tests.
Aetna agrees with CMS that no special program is necessary when making reimbursement determinations for gene-based diagnostics.
“The principles for genetics-based or personalized medicine-based technologies are the same as those principles that govern decision making for all areas of medicine. It’s important we stay focused on these principles,” Aetna’s Armstrong maintained. “There is a lot of interest in having some sort of exceptional process for genetic-based technologies but we should not run around really solid evidence-based decision making.”
But John Ridge, director of reimbursement services at Roche Diagnostics, previously complained to Pharmacogenomics Reporter that in holding Dx developers to the same evidence standards as pharmaceutical companies, payors may end up hindering the development of innovative tests.
Roche Genetics’ Lindpaintner acknowledged that while meeting insurance companies’ evidence demands is difficult for Dx shops, Roche is undertaking the appropriate studies to prove clinical validity and utility for AmpliChip.
“It’s not as easy as doing one or two trials with 1,000 patients over two years. … But how do you do a double-blind controlled study with a companion diagnostic?” Lindpaintner said. “You can do it. You can come up with a design. We’re in the process of doing it, but it’s not something that happens overnight.”
“One of the things that strikes me in a lot of the sessions that I sit in on … [is] that we find more reasons not to proceed with personalized medicine than to proceed with it and find reasons to go forward.”
According to Lindpaintner, the level of evidence being requested by insurance companies places Dx shops in uncharted territory.
“For the diagnostic industry that is a watershed event. They have never had to do this before,” he said, adding that traditionally Dx shops have developed gene-based diagnostic kits from data that had already been validated in academia.
“That’s what they know how to do and … those are rather cheap matters,” said Lindpaintner. “Now we’re talking about a diagnostic that by its very essence is more expensive, and given the value it provides it should be more expensive.”
FDA Approval and Cost-Effectiveness
The AmpliChip, the first FDA-cleared microarray assay, identifies genetic variations in the CYP2D6 and CYP2C19 genes. Researchers believe these two genes play a role in the metabolism of a broad range of drugs, including certain anti-depressants, anti-psychotics, anti-epileptics, proton pump inhibitors, oncologics, and beta-blockers.
Although widely prescribed antipsychotics such as haloperidol, risperidone, and thioridazine are metabolized by CYP2D6, Lindpaintner expressed concern that insurance companies may not deem AmpliChip particularly useful in identifying patients likely to benefit from anti-psychotic therapies.
“My personal worry is that we may never see [AmpliChip] be a great success in the field of prescribing psychothreapeutics, but we may see it being successful in prescribing tamoxifen. It’s just a different set of circumstances, a different indication,” Lindpaintner said.
Lesko defended AmpliChip’s utility with tamoxifen, and suggested that covering the test might lead to efficient use of healthcare dollars.
“If you have breast cancer and you’re taking tamoxifen, and you happen to be a 2D6 metabolizer, biology tells us you can’t possibly respond to the drug,” Lesko said. “So getting back to some things that [Armstrong] presented, it would seem very reasonable to reimburse people to get their 2D6 tested, to weed out the 10 percent that can’t possibly respond to the drug, so they can go on aromatase inhibitors, rather than wait five years and figure out that [tamoxifen] isn’t working.”
Aromatase inhibitors are significantly more costly than tamoxifen, which is a generic drug.
For Aetna, however, neither FDA approval nor cost-effectiveness estimates seem to matter as much as studies published in peer-reviewed literature illustrating clinical utility.
“We don’t cover everything, even those that have FDA approval,” Armstrong said. “I am highlighting [the] AmpliChip CYP450 test because it’s often used as one of the success stories, but it really has a long way to go from the point of view of evidence-based review.”.
Despite receiving a nod from the FDA, “more than half of the rate of response of drug metabolism is unrelated to CYP450 and to … drug-drug interaction,” she said. “So, it’s currently not covered.”