By Turna Ray
Since the American Recovery and Reinvestment Act was passed in February, the NIH has awarded approximately 80 grants totaling roughly $45 million to help pay for genomically guided personalized medicine projects, according to analyses conducted by GenomeWeb.
Since Oct. 6, the total number of ARRA grants in the NIH database was 12,789 and the total amount awarded was more $4.4 million, excluding funding for contracts.
The top 10 ARRA grant recipients in the PGx arena since the beginning of the program were for projects involving electronic health records, genomic disease risk in cancer, comparative effectiveness studies on genomic medicine, and PGx research into heart disease.
Below are details of the top 10, which were collected from a rough analysis of NIH ARRA awards based on a survey of project names and other key words.
The Vanderbilt Electronic Systems for Pharmacogenomic Assessment, or VESPA, project received the most ARRA funds, more than $5 million, to use de-identified data from electronic health records and genetic information from Vanderbilt University's DNA repository to investigate the genetic underpinnings for drug response.
The project, led by VU's Daniel Masys and Dan Roden, will also assess how useful EHRs in identifying genotypes and heterogeneously documented clinical phenotypes.
Another ARRA-backed EHR project is under way at the University of Virginia and led by William Knaus and Wendy Cohn, who received just under $2 million to create a Genome Enabled Medical Record. GenE EMR aims to "enable real-time clinical decision support for clinicians and their patients in user-friendly formats."
According to the project abstract, the system under development is designed to help collect and share family history and personal disease-risk information from genetic tests, and connect this information to clinical information, treatment records and patient outcomes.
The system will also display recommendations -- on the analytic and clinical validity, clinical utility, as well as ethical, legal, and societal implications -- for genomic and personalized medicine products designed to help treat and prevent cancer.
[ pagebreak ]
The ARRA package also doled out incentives to hospitals and physicians for the "meaningful" implementation of EHRs and includes penalties for those who do not move to such systems by 2015. This will likely urge many healthcare providers to invest in EHRs, which some industry observers believe are critical components of aligning comparative-effectiveness research and personalized medicine principles [see PGx Reporter 10-29-2009].
ARRA also enabled the US Congress to allocate $1.1 billion in grants for comparative-effectiveness research: $400 million to the NIH, $300 million to Agency for Healthcare Research & Quality, and $400 million to the Office of the HHS Secretary to create the Federal Coordinating Council for Comparative Effectiveness Research.
For instance, earlier this month the National Cancer Institute awarded $4 million to the Fred Hutchinson Cancer Research Center to help it develop Comparative Effectiveness Research in Cancer Genomics, or CancerGen, which will focus on assessing the predictive and prognostic value of genomic tools in treating cancer.
CancerGen's first study will investigate the predictive ability of Genomic Health's Oncotype DX test to determine which node-positive breast cancer patients will benefit from a tamoxifen-based chemotherapy regimen [see PGx Reporter 10-21-2009].
The NIH has also awarded around $2 million to researchers at the Kaiser Foundation Research Institute to study comparative effectiveness in genomic and personalized medicine in colon cancer, and nearly $2 million to the University of Pennsylvania for comparative effectiveness studies in genomic medicine.
Katrina Goddard, Lawrence Kushi, and Evelyn Whitlock of the Kaiser Foundation Research Institute will use the ARRA cash to evaluate several genetic tests related to colon cancer that could help physicians detect colon cancer sooner and help them make treatment decisions. The researchers plan to study how the genetic test results affect patients''treatment strategy, and whether they have different health outcomes when they get tested.
The researchers will then compare their own findings with published data and analyze the pharmacoeconomics of the colon cancer tests themselves.
Another ARRA grant recipient is Katrina Armstrong of the University of Pennsylvania, who will use $2 million in stimulus funding to develop a multidisciplinary center, called the Center for Comparative Effectiveness in Genomic Medicine, which will try to generate and synthesize evidence for introducing genomic tests into clinical cancer care.
The CCEGM will conduct observational and experimental comparative-effectiveness studies of genomic test that are ""clinically available or nearly clinically available."" As part of the project abstract, Armstrong noted pilot comparative effectiveness studies looking at the pharmacogenomics of nicotine addiction treatment; breast cancer SNP panels in risk screening and prevention; personalized treatment for non small-cell lung cancer; and CDKN2A/p16 testing and adherence to melanoma prevention behaviors.
Armstrong proposed reviewing published studies on the clinical validity of EGFR and KRAS mutations in predicting treatment response, a decision model of the use of SNP panels in breast cancer screening, and a cost- effectiveness model of nicotine metabolism markers in the treatment of nicotine addiction.
At Rockefeller University, Sohail Tavazoie will use his $2.5 million ARRA grant to perform discovery research into microRNAs that predict response to chemotherapeutics; Geoffrey Ginsburg of Duke University will use his $2 million grant to investigate the clinical effectiveness of cancer pharmacogenomics; and Stephen Skapek and Timothy Triche of Children's Hospital in Los Angeles will spend their $1.6 billion award to translate predictive cancer biomarkers into clinical practice.
Pharmacogenomics research into heart disease also received NIH ARRA funds.
Gerald Dorn of Washington University received more than $900,000 to research the genetic underpinnings of heart disease. Dorn and his team have formed a consortium comprising researchers from Washington University, the Mid America Heart Institute at the University of Missouri in Kansas City, and the University of Pennsylvania to "directly examine genetic risks, genetic modifiers, and pharmacogenomic interactions" of heart disease.
The researchers collectively have 7,700 study subjects who have or will undergo microarray analyses to identify candidate gene-disease associations. Then, the researchers will compare whether genetic factors improve outcomes over using just clinical profiling by validating gene associations through deep resequencing and conduct a prospective study of validated markers.
Furthermore, within the research consortium, Dorn and his team plan to synthesize existing research databases, establish centralized biomarker and genetics labs, create a web-based data-coordinating center, and create a data-safety monitoring board.
"The promise of large-scale genomics studies is that unsuspected gene-disease associations will identify markers of disease risk, and will provide novel insight into disease pathogenesis leading to innovative treatment strategies," the researchers said in the grant abstract. They are betting that genetic data will lead physicians to prescribe existing therapeutics to new diseases, thus "fast-tracking" the time from discovery to new therapeutics."
Also, Rima Kaddurah-Daouk of Duke University received approximately $2.5 million to study the links between genomics and metabolomics in response to certain cardiovascular drugs. The researchers in this project are inking a partnership between the Metabolomics Network for Drug Response Phenotype and two centers of excellence within the Pharmacogenomics Research Network to investigate the genomic mechanisms contributing to variations in response to cardiovascular drugs, particularly antihypertensives such as atenolol and hydrochlorothiazide and antiplatelet therapies such as Plavix and Aspirin.
The "union" between MNDRP and the PRN "will accelerate advances in our understanding of mechanisms of drug action and individual variation in the drug response phenotype making it possible to move toward a goal of truly 'personalized'or 'individualized'drug therapy," the researchers said in the grant abstract. Furthermore, within the project, the researchers plan to "hire and train researchers in metabolomics, a new field that has been earmarked as important to develop under the NIH roadmap initiative," as well as develop "standards for metabolomics, a national metabolomics database, and metabolic pathway database that couples information about human metabolic pathways with the human genome."