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FDA, CMS Parallel Review Pilot Opens Opportunities for Personalized Medicine Molecular Dx

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This article has been updated to note that Exact Sciences has previously said it will submit the Cologuard test for parallel review by FDA and CMS. Originally published Oct. 7.

By Turna Ray

The US Food and Drug
Administration and the Centers for Medicare & Medicaid Services this week launched a "parallel review" pilot for medical devices, under which they plan to coordinate regulatory and Medicare coverage reviews for up to five "innovative" devices per year.

Based on the criteria set out for devices that would be eligible for the parallel review process, molecular diagnostics in the personalized medicine field may be potential candidates for the pilot.

"Both agencies believe that overlapping evaluations by FDA and CMS for innovative products could speed consumer access to those new products by reducing the time span between marketing approval or clearance decisions and national coverage/payment determinations," an FDA spokesperson told PGx Reporter. "FDA and CMS are working together to identify areas in which they can collaborate to achieve these goals and parallel review provides one such opportunity."

The pilot comes after the two agencies announced their intent last year to establish a parallel review process, under which FDA and CMS would share data on drugs, biologics, and devices with the aim of reducing the time between regulatory approval and a national coverage determination for such products. The latest pilot is specifically focused on bringing to market new and "innovative" devices.

In order to be eligible to be reviewed simultaneously by the FDA and CMS, devices will have to fall in to one of the following categories: new technologies for which the sponsor has submitted a pre-investigational device exemption; devices for which the sponsor has submitted an original or supplemental pre-market review application or petitioned for a de novo review; or devices that fall in the Medicare Part A or Part B benefit category and aren't already being reviewed under a national coverage decision.

The pilot program is voluntary, and sponsors can opt out of the parallel review process. The agencies noted that although CMS and FDA will align reviews for a handful of tests through the pilot, this "will not change the existing separate and distinct review standards for FDA device approval and CMS coverage determination."

As previously reported by PGx Reporter sister publication GenomeWeb Daily News, molecular diagnostics firm Exact Sciences has said it will utilize the FDA/CMS parallel review process for Cologuard, a stool-based DNA colon cancer screening test based on a biomarker and platform technology licensed from MDxHealth. Exact plans to file a premarket approval application for the test with the FDA in the fourth quarter of 2012, at which point CMS will conduct its national coverage assessment for the test.

In announcing the parallel-review pilot, FDA and CMS acknowledged the currently disjointed nature of reimbursement and regulatory approval. "Often, device sponsors focus solely on obtaining FDA approval, only to find that Medicare coverage is not automatically forthcoming," the agencies said in a statement. "Both agencies rely on clinical data in reaching their decisions, and while the two agencies have distinctly different regulatory responsibilities, parallel review can reduce time between FDA approval and Medicare national coverage determinations."

Incongruent regulatory and reimbursement processes have been a major cause for concern among molecular diagnostics stakeholders who feel that aligning CMS's and FDA's requirements would bring more innovative tests to market and drive adoption of personalized medicine.

On the one hand, FDA approval of a molecular diagnostic doesn't make CMS any more likely to cover the test for the Medicare population. On the other hand, since molecular diagnostics can come to market as diagnostic kits or as laboratory-developed tests under the purview of CMS' Clinical Laboratory Improvement Amendments, tests can be reimbursed and not have FDA approval.

Test developers and labs complain that payor adoption often lags several years behind regulatory approval of a molecular diagnostic. For example, several firms have garnered FDA approval for genetic tests that gauge which patients are more likely to experience serious adverse events to the anticoagulant warfarin, but CMS and private payors still consider such testing investigational.

Several years after the FDA approved the first genetic test for warfarin sensitivity, CMS issued a "coverage with evidence development" strategy to pay for pharmacogenetic-based warfarin dosing when conducted in the context of a prospective, randomized-controlled trial that shows such an intervention improves outcomes for Medicare beneficiaries compared to the standard of care (PGx Reporter 5/6/2009).

Meanwhile, diagnostic developers and labs who have invested in the clinical validity and utility studies that payors demand for reimbursement — and have launched their diagnostics as laboratory-developed tests instead of FDA-approved kits — have fared better on the market.

As in the case of Genomic Health, the regulatory status of its Oncotype DX breast cancer recurrence test hasn't hurt the reimbursement prospects of the test in any way. Although Oncotype DX doesn't have FDA approval, but is marketed as a CLIA-certified laboratory-developed test, Genomic Health has secured reimbursement payment for its Oncotype DX breast cancer test from most of the major private payors in the US.

Although there has been significant industry support for simultaneous FDA/CMS reviews for many years, the two agencies have publicly balked at such suggestions, arguing that the regulatory agency and the government payor have distinct aims as defined by their separate legislative mandates and that without an act of Congress parallel reviews would not be possible.

However, last year, CMS and the FDA for the first time began openly discussing the possibility of parallel reviews. In June 2010, FDA Commissioner Margaret Hamburg and CMS Acting Administrator Marilyn Tavenner signed a memorandum of understanding in which the two agencies agreed to share information and expertise. The agencies have hinted that their data-sharing pact can potentially expand into areas beyond regulatory approval and Medicare coverage of new products. For example, the FDA can use Medicare claims data to conduct post-market surveillance of medical products.

As of Oct. 7, FDA and CMS began accepting submissions for devices that are eligible for parallel review. The pilot program will run for up to two years "with the possibility for extension," the agencies said. Each year the pilot is running, the agencies will accept "no more than three to five submissions."

The FDA spokesperson said that it will be up to sponsors to publicly announce whether their products are being reviewed under the parallel pilot.


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