Risk-Benefit Framework for Genetic Tests

描述（由申请人提供）：在过去十年中，基因分析的巨大技术进步为通过基因组学改善公众健康提供了一个重要但具有挑战性的机会。大多数情况下，基因检测的临床应用在提供给患者时并不为人所熟知或理解，数据的缺乏将是一个持续的问题。也许同样具有挑战性的是，基因测试的证据标准和评估其临床效用的方法尚不清楚，使基因组技术的转化途径复杂化。最近，在药物和生物制剂的监管决策中使用正式的风险效益分析已经引起了极大的兴趣。其中一种方法使用基于疾病的健康结果建模来预测干预措施对临床事件发生率、预期寿命和生活质量以及一系列可能结果的影响。我们认为这种方法对于评估影响健康结果的基因检测，以及向提供者和决策者传达潜在的临床益处、危害和不确定性尤其有用。该项目的总体目标是通过三个案例研究，建立一个正式的临床风险-收益框架，以促进基因组技术的转化途径；具体目标如下：(1)与利益相关者团体合作，利用华法林药物基因组学作为案例，制定定量风险-收益框架，以评估基因测试的临床效用；(2)通过将其应用于另外两个案例研究来评估框架的普遍性：a)早期乳腺癌妇女的基因表达谱，b)凝血或不良妊娠结局的孕妇的因子V Leiden检测；(3)通过与利益相关者群体达成共识的发展过程，评估和优化风险-收益框架的效用。这个转化研究项目将1)建立一个评估基因检测效用的证据和不确定性的框架，2)阐明目前可用的三种检测的证据基础，3)为临床医生和决策者提供一个工具，让他们了解基因检测的潜在利弊。这一方法将有助于加快整合、利用风险低但可能带来益处的基因检测和基于实践的证据开发，同时阻止过早使用构成重大健康风险的检测。7. 这个转化研究项目将通过以下方式帮助改善公众健康：1)建立一个评估基因检测效用的证据和不确定性的框架；2)澄清几种现有检测的证据基础；3)提供一个工具，教育临床医生和决策者了解基因检测的潜在利弊。这一方法将加速整合、利用和基于实践的证据开发风险低但看似有益的基因检测，同时阻止过早使用构成重大健康风险的检测。

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.