Conceding the need for publicly accessible information about the clinical and analytical validity of laboratory-developed genetic tests, the HHS Secretary’s Advisory Committee for Genetics, Health, and Society decided last week to mandate the development of a web-based registry designed to enhance the understanding and enhance transparency of the tests.
At a meeting it held in Washington, DC, last week, the SACGHS issued an overarching recommendation for the HHS to convene stakeholders, including other federal agencies, laboratory clinicians, patient advocates, and industry, to help the FDA further define its risk-based regulatory approach toward genetic tests.
The committee convened to discuss and finalize a set of draft recommendations it issued last year on the federal oversight of genetic tests. According to committee members, due to overwhelming stakeholder comments, the SACGHS decided that a “mandatory, publicly available, web-based registry that is well-staffed to maintain an accurate and current database would offer the best approach to address the information gaps” regarding laboratory-developed genetic tests.
SACGHS next month expects to finalize the draft report, called “US System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of HHS.” It plans to submit it to the HHS Secretary by the end of April and make it part of its final recommendations on the federal oversight of genetic tests.
According to the committee, the mandatory registry would include information on all LDTs, though it must still decide which agency would manage the database — the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, or the US Food and Drug Administration.
While the SACGHS felt “the concept of a mandatory registry offers promise … there are unresolved issues, including practical and legal questions, that require further analysis before a final decision can be made about how and where to implement the registry.”
To this end, the committee left it up to HHS to decide which agency should spearhead the registry. In the meantime, HHS “should use short-term voluntary approaches such as incentivizing laboratories to register with [the NIH-funded data repository] GeneTests and encouraging laboratories to make their test menus and clinical validity data for these tests publicly available on laboratory websites.”
The SACGHS further suggested that the CDC, CMS, and FDA convene a stakeholders meeting by September to decide the data elements that test developers should be required to submit to the registry. Additionally, HHS should perform a legal analysis to determine what statutory authority these three regulatory agencies have to require LDT developers to report these data points.
In comments to the draft recommendations, industry groups expressed the need for a mandatory registry of genetic tests. Particularly groups such as Johns Hopkins University’s Genetic Public Policy Center, Genetic Alliance, and the Coalition for 21st
Century Medicine have been advocating that the FDA create such a registry to collect data on a product for three to five years before deciding whether to subject that test to pre-market approval or 510(k) clearance [see PGx Reporter 02-06-2008].
“If you look at our webpage, we’ve approved expression arrays, microarrays, multiplex assays. We’re not afraid of technology. It’s the intended use. Even within the construct of IVDMIAs, it can be parsed … with some subtlety.”
“The FDA should exert some authority in this area but not do it in a way that stifles innovation,” SACGHS member and Genzyme Genetics President Mara Aspinall said at the meeting. “This is where the registry” comes in, giving the industry “at least a period of time before any pre-market review, given the massive change that this is for the industry.”
Traditionally, the FDA has practiced “enforcement discretion” over most laboratory-developed tests, which are overseen by CMS. But when the FDA decided it would regulate a more complex type of LDT called in vitro diagnostic multivariate index assays, test developers claimed that the resulting regulatory strategy would be inequitable, arbitrary, and hinder innovation. [see PGx Reporter 02-14-07].
The 1976 Medical Device Amendments to the Food, Drug & Cosmetic Act created three classes of devices, defined by the level of regulatory control issued, with Class III devices requiring the most stringent level of regulation: pre-market approval. According to the FDA’s draft guidance describing IVDMIAs, the tests will likely be Class II devices, requiring pre-market notification in the form of a 510(k) submission, or fall in the Class III category, requiring pre-market approval. However, critics of the guidance have said the agency’s approach is “technology based” and not “risk based.”
“This is a group you have to pull together to discern what ‘risk based’ is and which tests get a pre-market review and which ones don’t,” Marc Williams, SACGHS member and director of the Intermountain Healthcare Clinical Genetics Institute, said at the meeting. “So I think we’re endorsing the concept but we have some concerns about how that concept will be applied.”
The FDA, which is in the midst of finalizing the IVDMIA guidance, has maintained that it should regulate IVDMIAs because the technology behind them confers more risk on patients. During the meeting, Steven Gutman, director of FDA’s Office of In Vitro Diagnostic Device Evaluation, defended the agency’s risk-based approach.
“Even within the IVDMIA subgroup there are risks,” he said. “Certainly the transparency issue is important to us, but it wasn’t the technology per se. If you look at our webpage, we’ve approved expression arrays, microarrays, multiplex assays. We’re not afraid of technology. It’s the intended use. Even within the construct of IVDMIAs, it can be parsed … with some subtlety.”
Ultimately, the SACGHS agreed with the FDA’s approach to regulating LDTs. The committee felt that “applying the same regulatory framework to every genetic test is infeasible” from a time and cost perspective. However, the committee suggested “further analysis … to determine whether appropriate weight has been apportioned to risks associated with the novelty and complexity of the testing platform and technology.”
Muin Khoury, SACGHS member and director of CDC’s National Office of Public Health Genomics, said that “the important thing would be to put out the data that currently exists. [Establish] sort of the truth in advertising. That’s how we get back to the concept of the registry. As part of this process it’s time to put the data out.”