Risk-Benefit Framework for Genetic Tests

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DESCRIPTION (provided by applicant): The tremendous technological advances in genetic analysis over the past decade present a significant, yet challenging, opportunity to improving the public's health through genomics. Most often the clinical utility of a genetic test is not well known or understood at the time of its availability to patients, and the paucity of data will be an ongoing issue. Perhaps as challenging, the evidence criteria for genetic tests and the approaches for evaluating their clinical utility are unclear, complicating the translational pathway for genomic technologies. Recently, there has been significant interest in the use of formal risk-benefit analysis in regulatory decision making for drugs and biologics. One such approach uses disease-based health outcomes modeling to project the effect of an intervention on the incidence of clinical events, life expectancy, and quality of life, as well as a range of likely outcomes. We propose this approach will be particularly useful for assessing genetic tests intended to influence health outcomes, and communicating the potential clinical benefits, harms, and uncertainty to providers and policy makers. The overall goal of this project is to develop a formal clinical risk- benefit framework to facilitate the translational pathway for genomic technologies using three case studies; the Specific Aims are as follows: (1) Develop a quantitative risk-benefit framework for evaluating the clinical utility of genetic tests in collaboration with stakeholder groups, utilizing warfarin pharmacogenomics as a case example; (2) Assess the generalizability of the framework by applying it to two additional case studies: a) Gene expression profiling in women with early stage breast cancer, and b) Factor V Leiden testing for pregnant women with clotting or adverse pregnancy outcomes; (3) Evaluate and optimize the utility of the risk-benefit framework via a consensus development process with stakeholder groups. This translational research project will 1) develop a framework for assessing the evidence and uncertainty of genetic test utility, 2) clarify the evidence base for three currently available tests, and 3) provide a tool for educating clinicians and decision makers about the potential benefits and harms of genetic testing. This approach will help accelerate the integration, utilization, and practice-based evidence development of genetic tests that pose low risk but offer plausible benefit, while discouraging the premature use of tests that pose significant health risks. 7. Project narrative This translational research project will help improve the public's health by 1) developing a framework for assessing the evidence and uncertainty of genetic test utility, 2) clarifying the evidence base for several currently available tests, and 3) providing a tool for educating clinicians and decision makers about the potential benefits and harms of genetic testing. This approach will accelerate the integration, utilization, and practice-based evidence development of genetic tests that pose low risk but offer plausible benefit, yet discourage the premature use of tests that pose significant health risks.