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As CMS Ponders Adding Genetic Rule for CLIA Regs, Genetic Testing Players Consider Potential Outcome

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Following a request from the Genetic Alliance to create a genetic testing specialty under the Clinical Laboratory Improvement Act, the Centers for Medicare and Medicaid last week said that such an amendment is currently in clearance at the agency.

"There will be a regulation forthcoming," a CMS official told Pharmacogenomics Reporter sister publication GenomeWeb News last week. "It is a proposed rule that will solicit comments from the public."

The development, which follows a 2000 promise by CMS to look at the issue, is noteworthy for pharmacogenomics and molecular diagnostics test developers and reference labs because any new genetic testing rules added to CLIA would affect all clinical labs conducting genetic testing, including those who purchase tests from outside manufacturers.

Manufacturers, on the other hand, would be affected indirectly, if at all, though such regulation could validate their technologies by acting as a kind of government imprimatur.

The Genetic Alliance's request, made March 2 in an open letter to CMS Administrator Mark McClellan, follows a similar petition from the Genetics and Public Policy Institute, which also published an article in the February issue of Research Policy Alert critical of genetic test quality when used in pharmacogenomics. The institute plans to publish another article in Issues in Science and Technology on March 22 about direct-to-consumer genetic test quality and the concomitant need for a CLIA genetic specialty.


"Right now we're seeing about 900 genetic tests available — that goes up by about a hundred a year, and so that kind of volume, we really think, warrants a subspecialty that could oversee that area."

The two organizations believe that a CLIA genetic specialty is needed to assure the quality and reliability of data produced from a burgeoning number of genetic tests, especially pharmacogenomic tests, which are used to help make important clinical decisions.

"I remember hearing about this [testing specialty] three-plus years ago, and to me, it wasn't a question of 'if,' it was a question of 'when,'" said Bill Pignato, whose firm, William J. Pignato & Associates, consults diagnostics companies.

CLIA specialties already exist for tests in fields such as microbiology, bacteriology, syphilis, endocrinology, virology, toxicology, and hemotology. Despite the fact that genetic testing is performed as often as tests for some of these other indications, CLIA does not regulate them.

CMS, which oversees CLIA regulations, has established other subspecialties "at a much lower threshold" in terms of the number of tests of a particular type, said Genetic Alliance CEO Sharon Terry, who wrote the letter to CMS.

"Right now we're seeing about 900 genetic tests available — that goes up by about a hundred a year, and so that kind of volume, we really think, warrants a subspecialty that could oversee that area," Terry told Pharmacogenomics Reporter this week.

"We don't think these [certifiers] are ready to look at the complexities around putting together these pharmacogenomic tests particularly, and then of course the genetic tests as well," said Terry. No single event triggered Genetic Alliance's letter, said Terry.

Without regulated processes and results, genetic testing can be misrepresented and misused, she contended. In direct-to-consumer testing, for example, "there is a lot of concern that these tests don't work, or that people don't understand them, or [questions like], 'How can you possibly get an Alzheimer's test over the Internet?'" said Gail Javitt, a Policy Analyst at the Genetics and Public Policy Center at Johns Hopkins University

Moreover, concerns about direct-to-consumer testing are "symptom[s] of the lack of a coherent oversight system for genetic testing more generally," Javitt said. Whether any genetic test can be offered directly to consumers is a matter governed by state law, however, she added.

As evidenced by guidance documents like last year's voluntary submissions guidelines for pharmacogenomic data and last month's draft guidance for pharmacogenetic tests and tests for heritable markers, the US Food and Drug Administration can be credibly viewed as a motive force for pharmacogenomic and genetic testing.

But if the FDA approves a diagnostic for pharmacogenomic use, "there is nothing to stop a clinical laboratory from offering that same test [as a homebrew]," said Javitt.

The two routes to clinical testing have inconsistent conditions, Javitt said. "There are two paths [for genetic tests to reach consumers], so we're pointing out again that the current lack of a coherent oversight system can have a negative impact on the development and the promise of pharmacogenetics."

Any new genetic testing rules added to CLIA would affect all clinical laboratories conducting genetic testing, including those who purchase tests from outside manufacturers, while manufacturers would be affected indirectly, if at all.

Without knowing what possible changes might be made, it's hard to estimate the impact of a CLIA genetic testing specialty, said Matt Watson, CEO of CombiMatrix Molecular Diagnostics, a test manufacturer in the process of establishing CLIA certification. But "I wouldn't anticipate that their mission would change, and if that's the case, I don't see that it would impact us greatly one way or the other," he said.

For the patient, a subspecialty under CLIA would probably be a good thing, said Watson. It would also "validate what we're trying to do" and its importance, rather than lumping it in with other testing, he added.

Least Burdensome?

Any change in oversight is often accompanied with additional administrative burdens, and therefore additional cost burdens, as all companies know. "I'm sure it's going to mean more paperwork, and when you're bringing up new tests, of course you're going to have new standards to comply with that you're not used to complying with," said Watson. That burden is not a big concern, though, he said.

But most labs that stand to be affected by a CMS change probably won't be opposed to a genetic specialty, since the two organizations calling for the change are "focused on analytical validity and having appropriate proficiency-testing requirements that typically will apply if you have a subspecialty listed under CLIA," said Pignato, the consultant.

Johns Hopkins' Javitt and her colleagues feel that CMS cast a "very broad net" with a 2000 notice of intent to cover genetic testing, and industry comments on the document suggested that some parts would prove burdensome, such as a question about whether a clinical lab is required to document patients' informed consent, she said. "What's essential to quality is really this issue of proficiency testing, and 'Does the laboratory reliably know how to get the right answer?'" said Javitt.

When factors such as informed consent and genetic test counseling are removed from the equation, the extra burden upon laboratories is reduced, Javitt said.

The Genetic Alliance hasn't found people opposed to the idea of a genetic specialty, said CEO Terry. But Keith Batchelder, a consultant with Genomic Healthcare Strategies, said there are "all these mixed opinions about whether [a genetic specialty would be] good or bad. I don't think there's a consensus."

"I think that there are many areas where regulations — confidentiality, security, quality control — will be necessary in the new world of pharmacogenetics and pharmacogenomics," said Batchelder. But "there are always unintended consequences related to establishing regulations," often because policies cannot anticipate future needs perfectly, while policies established to fix existing problems can have blind spots.

It may be the case that diagnostics makers would prefer a CLIA genetic specialty over increased oversight by the US Food and Drug Administration — which the Genetic Alliance believes could be an option. The FDA's latest guidance document relevant to the field, Pharmacogenetic Tests and Genetic Tests for Heritable Markers, "might be a salvo over the bow" that suggests that the FDA may be looking at taking over regulation of these tests, said Terry. The FDA's Center for Devices and Radiological Health released the guidance document in early February.

But Steve Gutman, director of the FDA's Office of In Vitro Diagnostic Device Evaluation and Safety, wrote in an e-mail to Pharmacogenomics Reporter this week that the guidance should not be interpreted as a message. "The CDRH guidance was intended to clarify premarket review information that is appropriate for a new genomic or genetic test, nothing more and nothing less (and certainly with no hidden message to CMS). Of course, we do hope the guidance, once final, will be valuable to all stakeholders."

"I would have some concerns about the FDA taking it over from CLIA" because it has already developed a solid understanding and experience with testing, said CMD's Watson. At the same time, the FDA is "heavily burdened in trying to take on the IVD industry and the drug industry," although it has periodically signaled its interest in regulating clinical laboratory testing, he said.

— Chris Womack ([email protected])

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