Comparative Effectiveness in Genomic Medicine

描述（由申请人提供）：基因组学的进展有可能通过将干预措施针对那些将获得最大益处并经历最低不良事件风险的个体来改善医疗保健的提供。更有效地确定干预目标特别有吸引力，因为这是少数既能改善结果又能降低成本的方法之一--这是医疗保健改革毫无疑问的最佳点。然而，基因组医学在达到这个最佳点之前还有很长的路要走。一些需要的是发现基因-疾病的关联，从而导致临床基因检测的发展。但是，越来越多的需要不在于开发测试，而在于决定使用测试是否比我们目前正在做的更好-即比较有效性。该项目的总体目标是建立一个协调的多学科中心，用于生成和合成证据，以支持将基因组检测转化为癌症预防，筛查，诊断，治疗和生存的改善。该中心（名为基因组医学比较有效性中心或CCEGM）将涉及两个主要科学组成部分：（1）证据生成;（2）证据合成和建模。证据生成部分的目标是对临床可用或接近临床可用的基因组检测的比较有效性进行观察和实验研究。本提案中包括四项原则证明、试点研究：（1）尼古丁成瘾治疗的药物基因组学;（2）乳腺癌风险筛查和预防中来自乳腺癌SNP面板的增量信息;（3）非小细胞肺癌的个性化治疗;（4）CDKN 2A/p16检测和坚持黑色素瘤预防行为。证据合成部分的目标是使用统计和建模方法将现有证据汇集在一起，以提供有关临床实践的建议。包括三个相应的证据合成试点项目：EGFr和K-ras突变在预测治疗反应中的临床有效性的系统评价，在乳腺癌筛查中使用SNP面板的决策模型，尼古丁代谢标记物在尼古丁成瘾治疗中的成本效益模型。 公共卫生相关性：基因组学的进步有可能改善卫生保健的提供。 越来越需要决定使用基因组测试是否比我们目前正在做的更好-即比较有效性。该项目的总体目标是建立一个协调的多学科中心，用于生成和合成证据，以支持将基因组检测转化为癌症预防，筛查，诊断，治疗和生存的改善。

DESCRIPTION (Provided by the applicant): Advances in genomics have the potential to improve the delivery of health care by targeting interventions to individuals who will receive the greatest benefit and experience the lowest risk of adverse events. More effective targeting of interventions is particularly appealing because it is one of the few approaches that can both improve outcomes and reduce costs- the unquestioned sweet spot of health care reform. However, genomic medicine has a long way to go before it gets to that sweet spot. Some of what is needed is discovery of gene-disease associations that lead to the development of a clinical genetic test. But increasingly, the needs lie not in developing the test but in deciding whether using the test is better than doing what we are currently doing - i.e. comparative effectiveness. The overarching goal of this project is to develop a coordinated, multidisciplinary center for the generation and synthesis of evidence to support the translation of genomic tests into improvements in cancer prevention, screening, diagnosis, treatment and survivorship. The center (entitled the Center for Comparative Effectiveness in Genomic Medicine or CCEGM) will involve two primary scientific components: (1) evidence generation; and (2) evidence synthesis and modeling. The goal of the evidence generation component is to conduct observational and experimental studies of the comparative effectiveness of genomic test that are clinically available or nearly clinically available. Four proof of principle, pilot studies are included in this proposal: (1) pharmacogenomics of nicotine addiction treatment; (2) incremental information from breast cancer SNP panels in breast cancer risk screening and prevention; (3) personalized treatment for non small cell lung cancer; and (4) CDKN2A/p16 testing and adherence to melanoma prevention behaviors. The goal of the evidence synthesis component is to use statistical and modeling methods to bring together existing evidence to inform recommendations about clinical practice. Three corresponding evidence synthesis pilot projects are included: a systematic review of the clinical validity of EGFr and K-ras mutations in predicting response to treatment, a decision model of the use of SNP panels in breast cancer screening, a cost- effectiveness model of nicotine metabolism markers in treatment of nicotine addiction. PUBLIC HEALTH RELEVANCE: Advances in genomics have the potential to improve the delivery of health care. Increasingly, there is a need to decide whether the use of genomic tests is better than doing what we are currently doing - i.e. comparative effectiveness. The overarching goal of this project is to develop a coordinated, multidisciplinary center for the generation and synthesis of evidence to support the translation of genomic tests into improvements in cancer prevention, screening, diagnosis, treatment and survivorship.