Comparative Effectiveness in Genomic Medicine

描述（由申请人提供）：基因组学的进步有可能通过针对个体的干预措施来改善医疗保健的提供，这些个体将获得最大的益处，并经历最低的不良事件风险。更有效地针对干预措施具有特别的吸引力，因为它是既能改善结果又能降低成本的为数不多的方法之一——这无疑是卫生保健改革的最佳点。然而，基因组医学在达到最佳状态之前还有很长的路要走。需要做的是发现基因与疾病之间的关联，从而发展临床基因检测。但是，越来越多的需求不在于开发这种测试，而在于决定使用这种测试是否比我们目前所做的更好——即相对有效性。该项目的总体目标是建立一个协调的多学科中心，以产生和合成证据，以支持将基因组测试转化为癌症预防、筛查、诊断、治疗和生存方面的改进。该中心（名为基因组医学比较有效性中心或CCEGM）将包括两个主要的科学组成部分：(1)证据生成；(2)证据合成与建模。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性和实验性研究。本提案包括四项原理证明，试点研究：(1)尼古丁成瘾治疗的药物基因组学；(2)乳腺癌SNP面板在乳腺癌风险筛查和预防中的增量信息；(3)非小细胞肺癌的个性化治疗；(4) CDKN2A/p16检测与黑色素瘤预防行为的依从性。证据综合部分的目标是使用统计和建模方法汇集现有证据，为临床实践提供建议。三个相应的证据综合试点项目包括：EGFr和K-ras突变预测治疗反应的临床有效性的系统回顾，在乳腺癌筛查中使用SNP面板的决策模型，尼古丁代谢标志物治疗尼古丁成瘾的成本-效果模型。

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.