The Health Benefits Of Genomics

Main Category: Genetics
Also Included In: Biology / Biochemistry
Article Date: 24 Nov 2008 - 3:00 PDT

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Obsolete models of research support and regulatory guidance severely threaten the promise of genetic medicine, writes Center Director Kathy Hudson in the November issue of Health Affairs. She argues that useful clinical and public health applications of genetic research can only be achieved by replacing outdated funding and regulation models with new approaches to funding translational research, development of evidence-based clinical guidelines, and robust regulation of genetic tests.

Prior to the Human Genome Project, writes Hudson, genetics research focused on "harvest[ing] low-hanging genetic fruit" - identifying the most obvious gene mutations whose effects were so strong they were easily detected, and their clinical utility immediately evident. Today, however, the game has changed. Researchers using genome-wide association studies are working to identify the many genetic contributors to common disorders such diabetes, cardiovascular disease, and prostate cancer. Such variants generally have very weak associations with disease and thus have uncertain clinical relevance. However, they can serve to identify the sometimes surprising molecules and pathways involved in pathogenesis. This research holds great potential for identifying new targets for treatment and prevention - but the fulfillment of that promise demands greater funding for translational research.

Hudson argues that the disproportionate emphasis on discovery research has resulted in a deluge of basic research discoveries, with no way of moving these discoveries into useful clinical application. She further notes that this imbalance has allowed the propagation of costly and unproven genetic tests, which "serve only to confuse the public to the detriment of their pocketbook - and, potentially their health - and to undermine public confidence in genetic medicine."

Hudson draws attention to the absence of a cost-effective means of evaluating the usefulness of genetic tests, noting that the "gold standard" of a randomized clinical trial may be too expensive and cumbersome for genomic applications. On the other hand, she notes, foregoing such a process could lead to companies or clinicians dispensing genetic "advice" that turns out to be of questionable value, or, worse, may undermine sound medical counsel.

Hudson presents several proposals for correcting these problems. She identifies as a model the work of the Evaluation of Genomics Applications in Practice and Prevention Working Group convened by the Centers for Disease Control and Prevention, which produced evidence reviews and evidence-based guidelines for the use of variants in cytochrome P450 (CYP450) to guide treatment, drug choice, and dosage for certain antidepressants. However, she explains that such reviews need to be "accompanied by regulatory approaches that employ a risk-based paradigm that doesn't sweat the small stuff, but still keeps unsafe tests out of the marketplace and closely polices the claims made by testing companies about their wares."

Hudson also recommends the Food and Drug Administration implement a tiered review process for all laboratory-developed tests, with a special focus on "high-risk" tests that address serious disease, and yield information patients can use to guide medical decisions. She also advises adoption of a recommendation passed down by the Secretary's Advisory Committee on Genetics, Health, and Society to develop a mandatory genetic testing registry, cataloging data on genetic tests' analytical and clinical validity, which would then be available for health care providers and the public to inform their decisions about whether a test is appropriate. Finally, she implores the Federal Trade Commission to take action to stop false and misleading claims made by purveyors of genetic tests directly to consumers.

These recommendations can be implemented only under an umbrella of broader change, according to Hudson. "All of these suggestions," she writes, "presuppose a funding environment where disproportionate emphasis on discovery research is balanced by funding for translational research to establish the validity and utility of new genetic tests, development and dissemination of health professional guidelines, and effective regulation of genetic tests." - Sara Brinda

Hudson, Kathy. The health benefits of genomics: Out with the old, in with the new. Health Affairs 27: 1612-1615.

Center report - Public Health at Risk: Failures in Oversight of Genetic Testing Laboratories

Javitt, Gail. In Search of a Coherent Framework: Options for FDA Oversight of Genetic Tests. Food and Drug Law Journal 62: 617-652.

The Genetics and Public Policy Center - Johns Hopkins University
http://www.dnapolicy.org