Originally published June 15.
By Turna Ray
The Centers for Disease Control and Prevention's GAPPNet project last week announced several new online resources for gathering information on ongoing studies related to public health, including a searchable database of genomic applications and a new open-access journal that publishes evidence reviews and summary articles on the validity and utility of genetic tests.
GAPPNet, short for the Genomic Applications in Practice and Prevention Network, is an effort led by the CDC's Office of Public Health Genomics and NCI's Division of Cancer Control and Population Sciences that convenes personalized medicine stakeholders to translate advances in genomic research into useful medical products and actionable guidelines (PGx Reporter 07/15/09).
In a Genetics in Medicine article last year, Muin Khoury, director of CDC's Office of Public Health Genomics, and others, outlined the four aims of GAPPNet: convening individuals and groups conducting genomics translation research, programs, and policy activities; sponsoring new translational research; synthesizing and evaluating available research findings; and developing and disseminating "validated, useful genomic knowledge and applications for use in medicine and public health."
The new GAPPNet services launched last week address these aims.
The Office of Public Health Genomics has revamped the GAPPNet website from an earlier version, which primarily provided information about what the project intended to do and meetings stakeholders had convened. The site now provides information about genomic technologies, policies, and new research. Furthermore, the site allows users to add to the body of knowledge about genomic technologies, question technology reviews posted by collaborators, and check out on an interactive map where the latest translational genomics projects are taking place.
The key to advancing GAPPNet's translational goals is the GAAP Knowledge Base: a searchable database of genomic applications that provides healthcare providers information on tests' availability, indication, clinical validity, and clinical usefulness. The two components of GAPP KB are GAPP Finder, a database of genomic applications, and the Evidence Aggregator, a tool for searching reports, reviews, recommendations, and guidelines on genomic applications.
Simultaneously, GAPPNet launched a new journal utilizing Google's Knol platform, which facilitates an online collaborative approach to conducting evidence reviews vetted by an expert review board. The open model of the Evidence for Genomic Applications Journal allows readers to comment on the reviews, pointing out new data or inaccuracies.
There are several gene mutation databases currently in use by genomics researchers and healthcare providers, such as the Pharmacogenomics Knowledge Base, which collects published data on genetic variations linked to drug response; and the Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff, which provides data on more than 72,000 gene alterations linked to human disease.
However, GAPPNet appears to be the first effort to embrace an open platform through which researchers, doctors, and the public can collaborate on gathering evidence and communicate about the available data about genomic technologies. Also, unlike these existing data repositories on gene mutations, GAPPNet's database will "focus on clinical validity and utility and health impact and not only on basic or early translational research," Khoury explained.
Furthermore, GAPPNet may eventually be linked to a genetic testing registry under development by the National Institutes of Health. At a meeting this week of the HHS Secretary's Advisory Committee on Genetics, Health, and Society, Kathy Hudson, chief of staff at NIH's Office of the Director, requested input from the committee and the public on the data elements to include in the voluntary online agency that are reasonable and not overly burdensome for companies.
Hudson informed SACGHS that the NIH would not double-check the accuracy of information submitted by companies to the registry, operating on good faith that industry players would not deliberately submit false data to try to "mislead the government."
Following, Hudson's presentation, Khoury noted that GAPPNet's new genomic technologies database would "go hand-in-hand" with NIH's genetic test registry. The GAPPNet website "already links to the [NIH registry] website under construction, and we are actively talking to the NIH," Khoury told Pharmacogenomics Reporter this week.
In a recent request for information, NIH suggested that the genetic test registry will likely invite the participation of direct-to-consumer genomics firms ─ such as Pathway Genomics, 23andMe, Navigenics, and others ─ which have recently fallen under regulatory and congressional scrutiny (PGx Reporter 06/11/10). Khoury similarly said that GAPPNet will also review and list clinical validity and utility data of tests offered by DTC genomics firms.
In Khoury's view, GAPPNet's emphasis on open discussion about available and missing evidence will be the driving force helping to close the translational gap between discovery research and useful, validated, marketed products benefiting public health.
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"By uncovering on an ongoing basis what we know and what we don't know … providers and consumers can be informed, as well as researchers," Khoury said. "In addition, GAPP KB has a database of ongoing translational research in genomics"
GAPP KB is currently in beta testing mode. According to Khoury, since September 2009 GAPPNet has been curating evidence on genomic technologies and GAPP KB currently features information on approximately 180 genomic tests.
In an effort to provide an example of this new resource to readers, Pharmacogenomics Reporter searched for the term "warfarin" in both GAPP Finder and Evidence Aggregator.
The term searched under GAPP Finder yields one result, which informs the visitor that CYP4F2 rs 2108622 (V433M) and CYP2C9*5 genotyping may be conducted in patients with thrombophilia prior to their treatment with warfarin. Upon clicking on that result, one learns that Osmetech's eSensor XT-8 Warfarin Sensitivity Plus Test gauges the CYP4F2 allele in combination with variations in CYP2C9 and VKORC1 genes.
According to the information available through GAPP KB, the visitor learns that although the CDC's Evaluation of Genomic Applications in Practice and Prevention initiative has reviewed the utility of CYP450 polymormphisms in non-psychotic depression patients treated with selective serotonin reuptake inhibitors, the group has not yet reviewed the utility of these SNPs in dosing warfarin for thrombophilia patients.
But upon searching for the term "warfarin" using the Evidence Aggregator function, the visitor is taken to a review of the available evidence on genetic testing to guide warfarin dosing written by Daurice Grossniklaus of the Office of Public Health Genomics.
The entry, last updated on April 29, includes a description of CYP2C9 and VKORC1 testing, the public health importance of such testing, and published recommendations regarding the intervention from the American College of Medical Genetics and the Centers for Medicare & Medicaid Services. The review then summarizes the available evidence on the analytical and clinical validity, as well as the clinical utility, of genomically guided warfarin sensitivity testing.
A search for the anti-platelet drug Plavix (clopidogrel), yielded a different scenario in terms of available evidence and applications.
According to available information on GAPP Finder, genetic testing may be conducted in patients with coronary artery disease "unlikely to respond to typical doses" of Plavix, or "to assess risk for subsequent death, myocardial infarction, stent thrombosis, and stroke because of insufficient clopidogrel-induced platelet inhibition." However, a search for the term "Plavix" yields no results in Evidence Aggregator.
What Do You Knol?
GAPPNet describes the Evidence for Genomic Applications Journal as an "open access online journal that will publish evidence reviews and summary articles on the validity and utility of genetic tests and other applications of genomic technologies."
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The journal's content is published via Knol, a Google Beta platform for sharing knowledge in collaborative projects such as GAPPNet. The platform allows readers to comment on the published evidence reviews.
"We need independent evaluation of genomic applications and not only what is submitted as part of a registry," Khoury said. "This is especially crucial for clinical utility."
It seems anyone can submit an evidence review, but the submission will be vetted by a panel of genomics experts.
The chief moderators of the journal are Khoury, Marta Gwinn, Dave Dotson, and Ralph Coates of CDC's Office of Public Health Genomics. Additionally there are more than 40 expert moderators listed on the site from universities, other federal agencies, payors groups, and hospitals. Anja Wulf of the Centers for Disease Control and Prevention is the technical editor of the journal.
Currently, the main page of the journal highlights four evidence reviews on VKORC1 and CYP2C9 testing for warfarin sensitivity by Grossniklaus; CYP2D6 testing to predict tamoxifen response by Issa Dahabreh, Teruhiko Terasawa, Thomas Trikalinos, and Peter Castaldi; tumor gene expression in breast cancer patients by Cecelia Bellcross and Dotson; and Oncotype DX gene expression profiling in stage II colon cancer by Elizabeth Webber, Jennifer Lin, and Evelyn Whitlock.
Contributors to the journal are instructed to set up a Google account to utilize the Knol features. Currently, the journal is only accepting brief evidence summaries focusing on the analytic validity, clinical validity, and clinical utility of genetic applications. Summaries submitted to the journal can be based on longer evidence reviews that have been previously published or are intended for publication in other journals.
Of the currently featured evidence reviews, the Oncotype DX test for colon cancer is the only one for which reviewers provide information on test "limitations," and an overall "conclusion" about the utility of the test based on currently available evidence. This is likely due to the fact that no professional societies have reviewed the test with regard to its clinical and analytical validity, or clinical utility.
According to the reviewers, the majority of evidence on this test has been presented as initial validation studies and much of the data is presented in abstract form and not as complete publications. As a result, they conclude that there is currently not enough evidence for a full evaluation of this assay.
"Although Genomic Health launched the Oncotype Dx colon cancer assay worldwide in January 2010, additional research is clearly needed before the value of this assay for clinical practice can be determined," the reviewers wrote.
Using available features on Knol, visitors can comment on the review currently posted in the Evidence for Genomic Applications Journal.
"Readers who are aware of updated information on a topic can add it to the Comments section following the summary, where it will be published after approval by the editors," GAPPNet informs potential contributors to the journal. "When sufficient new data become available, a new summary can be submitted for publication, either by the original author or by new authors."