Some researchers have argued that all genomic tests should be approved by the FDA, but that scenario is extremely unlikely, White said. For example, the path to FDA approval for a whole genome sequencing instrument and reagent system is currently unclear. Such a system would have complex intended uses, accuracy problems, no gold standard for comparison, rapid technical obsolescence, and a potential requirement for lengthy and costly prospective treatment-by-genotype clinical outcome studies. In addition, it is difficult for manufacturers that have to produce a system with validated reagents and software to compete with laboratories that develop tests under CLIA that use research-use-only instruments and that can update software and reagents as needed. “There is an uneven playing field that will prevent any of these tests from reaching FDA-approved instrument systems for decades,” said White.

A major hurdle to genomic-based medicine is the lack of a national, dynamically updated, interpretative database of evidence for the clinical utility of genetic variants, White said. Not every CLIA lab will be able to maintain and update a database of all its clinically useful variants and convey those updates to patients and physicians. Without evidence of clinical utility and cost-effectiveness, private and public payers may default to nonreimbursement. The government could have an extremely useful role in standardizing this information, said White, who suggested that the 100K Foodborne Pathogen Genome Project1 may be a model to emulate.

The basis for reimbursement of whole genome sequencing remains uncertain, he observed. Except perhaps for cancer indications, single clinical indications may not be cost-effective, said White. Furthermore, because of issues with accuracy, targeted confirmatory testing of some actionable variants identified by whole genome sequencing may be necessary and will increase overall costs. Given these uncertainties, White asked, how can the cost-effectiveness of whole genome sequencing be assessed for application over a lifetime?

Professional organizations need to develop guidelines for reporting genetic variants to patients and providers, according to White. Also, providers and patients are going to want evidence that a test will make a difference in treatment.

Stakeholders may need to accept different evidentiary standards for the clinical utility of tests for different medical conditions, White said. Also, the government will need to continue to support prospective randomized clinical outcome studies, with studies prioritized by disease area. Studies supported by the Patient-Centered Outcomes Research Institute could contribute to this goal.

Cost-effectiveness studies are not terribly expensive, said White, and


1 See (accessed March 19, 2013).

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