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SACGHS Debate Changes to Draft PGx Report; Final Will Be Released March ’08

WASHINGTON, DC -- Members of the HHS Secretary’s Advisory Committee on Genetics, Health, and Society last week voted to change parts of a report on pharmacogenomics after discussing public comments to the draft version.
The final version of the report is slated to be released in March 2008.
The SACGHS released the draft report, “Realizing the Promise of Pharmacogenomics,” in March of this year. The report was available for public comment from March 23 to June 1.
According to SACGHS, the majority of comments came from professional groups, such as the Pharmaceutical Research and Manufacturers of America and the Personalized Medicine Coalition, as well as from individual academics, health care providers, and researchers.
Recurring themes in the public comments included the criticism that the draft report was too optimistic about the long-term potential of PGx; a recommendation for more discussion of international efforts and public-private collaborations; and a better definition of PGx. Several comments also asked the committee to address the oversight of genetic tests.
SACGHS earlier this month issued a separate draft report on the regulatory oversight of genetic tests [see PGx Reporter 11-14-2007]. 
The public comments also recommended that the federal government encourage stakeholders in industry and academia to collect DNA to facilitate clinical trials for PGx research; noted the need for criteria to define the types of PGx information that should be included in a drug label; requested increased emphasis on the need for clinical effectiveness evidence to secure payor reimbursement; and asked that the reimbursement of PGx products should be value based.
Additionally, there was some disagreement to whether genetic counseling will be required for patients and physicians using and prescribing genetic tests.
Following the receipt of the public’s recommendations, the committee organized the draft report into three themes: research and development; gatekeepers; and implementation of PGx to improve outcomes in clinical and public health practice.
During the meeting SACGHS members debated the content, scope, and language of each of its 15 recommendations and 37 subparts. Three prominent discussions among committee members included the US Food and Drug Administration’s Voluntary Genomic Data Submissions Program, the development of PGx products for smaller markets, and the reimbursement for PGx products.
With regard to the FDA’s VGDS program, the SACGHS initially recommended that the “NIH should encourage grantees and contractors to participate in FDA’s Voluntary Genomic Data Submission program to ensure consistency in data standards that may affect drug prescribing.”
However, some members felt that HHS should require, instead of merely encouraging, grantees and contractors that receive the department’s funding to participate in VGDS. Some members felt that language requiring participation in a voluntary program would cause confusion. Others suggested that the HHS should convene appropriate agencies to lay out policies for when VGDS would be a requirement.
Meeting participant Steven Gutman, director of the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, moved to change the wording of the recommendation to emphasize that voluntary genomic data submissions should really be done in the exploratory phase of drug or diagnostic development. Without this distinction, the FDA may be overwhelmed by inappropriate submissions, Gutman suggested.
“VGDS is an exploratory process,” Gutman said. “As [the program] gains experience, it will start to create guidances and documents and it doesn’t need to keep reinventing the wheel.
“So [if] someone comes along with the third model of a particular kind [of genomic data], they don’t really need to submit again to the VGDS because that route has been established,” he added. “Because we at the FDA’s end don’t really have the resources, depending on how generous NIH funding in this area is, to start looking at just dozens” of superfluous submissions.
Earlier this year, Felix Frueh, associate director of genomics at the FDA, said he has seen an increase in the number of submissions to the program from drug companies wishing to “strategically” populate Phase III trials with genetically favorable volunteers. Particularly, Frueh has said that the agency has noted increasingly complex data submissions to the program [see PGx Reporter 01-03-2007].
“[W]hen you’re playing around with genomic data in the context of the drug, the VGDS really hits the spot, and when you have a companion diagnostic that’s on the way and you need to start thinking about a pre-IDE or a protocol review by the center for devices,” Gutman said at the SACGHS meeting.
Additionally, Gutman encouraged the committee to note in the report that even in developing diagnostics with NIH funding, test developers should be aware of FDA’s regulatory requirements for diagnostics. Test developers should read FDA guidance documents to familiarize themselves with the idea that their research will generate a product that will have “certain obligations about quality control and following the protocol.”

Once the sponsor realizes that it will “need both [drug and diagnostic] as bride and groom to enter the marketplace, then [the FDA is] the wedding hall.”

Companies should only submit to the VGDS program in the discovery phase, when they are still trying to figure out whether their genomic findings will yield a drug or a companion diagnostic as well. Once the sponsor realizes that it will “need both [drug and diagnostic] as bride and groom to enter the marketplace then [the FDA is] the wedding hall,” Gutman said.
Given these suggestions, the committee members voted to alter this recommendation to state: “HHS should require grantees and contractors as appropriate to participate in FDA’s VGDS program during the exploratory phase of drug development and/or the pre-IDE review process in situations where pharmacogenomic diagnostics are thought to be essential to clinical drug use.”
Another point of debate was how to encourage the development of PGx products in small disease populations. Due to the difference in the disease prevalence thresholds for orphan drugs and orphan devices, there was some concern among committee members that co-development of drug/diagnostic combination products in smaller disease markets would not be encouraged.
A drug is granted orphan status when 200,000 people or less are affected by the disease. For diagnostics, 4,000 people or less have to be impacted by the illness to garner orphan status. This incongruence “could favor the development of PGx drugs but not their companion diagnostics,” the committee noted.
“The fundamental premise that I’m concerned about is that for orphan drugs the system works as an incentive, said Mara Aspinall, SACGHS member and Genzyme Genetics president, who requested that any recommendation from the committee emphasize the need to incentivize development of PGx diagnostics along with drugs. “For orphan devices the system currently works as a disincentive, with more restrictions.”
The committee ultimately settled on the following recommendation: “HHS should engage all stakeholders in identifying and providing incentives to encourage the development of pharmacogenomics drugs and diagnostics, especially for smaller patient populations and/or markets.”
Finally, significant debate surrounded the reimbursement for PGx products. Initially, the draft recommendations stated that if a PGx test shows it enhances safety and effectiveness in clinical management or provides greater value over covered services, then public and private health plans should provide coverage for the test.
However, many of the committee members noted that such a recommendation has no teeth since it is outside the HHS Secretary’s oversight scope. The secretary only has purview over CMS-related payors, not over private payors.
Additionally, committee members noted that the Secretary should clarify with CMS whether PGx tests are considered a preventative service, and therefore will not be covered by CMS due to legislative statutes excluding such coverage.
“You’re telling Medicare how to make coverage decisions, and it’s not consistent with how CMS makes those decisions,” said Marc Williams, committee member and director of the Intermountain Healthcare Clinical Genetics Institute, in Salt Lake City.
Meeting participant Barry Straube, chief medical officer at the Centers for Medicare and Medicaid Services’ Office of Clinical Standards & Quality, noted that CMS bases its coverage decisions on comparative effectiveness metrics and cost-effectiveness. CMS does not look at the value of the test. The coverage of preventative tests will require an act of Congress, Straube added.
Finally, Straube suggested that in the matter of reimbursement of PGx tests, HHS ask CMS to produce a guidance document for the reimbursement of PGx tests. In crafting this document, CMS would survey the private sector to gauge what types of tests private payors are willing to cover.
Straube suggested the committee completely do away with its original recommendation on reimbursement for PGx tests, and instead recommend to the “Secretary to ask CMS to produce a guidance document on current status of genetic testing as it relates to pharmacogenomics, including surveying the private sector to look at what’s extant in that setting, and make some recommendations to him as to what options are available,” Straube said.
The committee settled on the following language: “CMS should develop a guidance document detailing current Medicare coverage and reimbursement of pharmacogenomics. In doing so, CMS should survey private health plans to identify differences between Medicare and private health plan coverage, as well as future coverage issues.”
This survey will help CMS compare private coverage policies with restriction under Medicare, and align them if possible, Straube noted.
After finalizing the language of the report last week, the committee plans to ready the final version of the report during the rest of this year, and send this version to the Secretary by February of next year. The report is slated for public release in March.

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