Integrated, Individualized, Intelligent Prescribing (I3P)

描述（由申请人提供）：人类基因组计划产生的一个广泛持有的愿景是使用新获得的遗传信息来指导个体患者的预防和治疗决策。检验这一概念的一个治疗领域似乎特别成熟，那就是药物基因组学，即治疗反应的可变性包括基因组成分。生殖系和体细胞肿瘤基因的共同变异是药物反应变异性的一个越来越被广泛认识的因素，因此，基因型指导治疗的建议正在被颁布。通过在多个基因组网络中的领导地位，范德比尔特一直处于药物基因组学发现和将这些知识转化为当地临床实践的最前沿。然而，很少有机构或从业者拥有将基因数据纳入常规药物处方的程序和工具。在本提案中，我们通过建立一个将基因组医学整合到不同医疗保健环境中的计划来实现这一实践。集成、个性化和智能处方（I3P）项目的目的是执行一个多站点演示，证明在电子健康记录（EHRs）中集成遗传数据可以改善医疗保健。我们将建立必要的流程和基础设施，以便在不同的医院和电子病历环境中传播临床基因检测、结果报告和决策支持。鉴于药物不良反应（adr）是发病率和死亡率的主要原因，美国食品和药物管理局（FDA）将越来越多的公认变异作为疗效和毒性的介质，以及“药物基因”中变异携带者相对缺乏耻辱感，本应用侧重于药物基因组学。该项目将建立在范德比尔特大学正在进行的两项临床基因分型工作的基础上：1)药物基因组资源用于增强护理和治疗决策（PREDICT）项目，该项目对184种高价值生殖系药物基因组变异进行前瞻性测试，包括与氯吡格雷、华法林和辛伐他汀相关的变异；2)个人癌症医学倡议组织（PCMI），定期对肺癌和黑色素瘤进行多重肿瘤基因突变检测，以指导治疗。I3P将利用范德比尔特大学现有的专业知识、信息学、实验室基础设施和资源，在“早期采用者”的三个不同医疗保健系统中实施基因组医学。这些医疗保健系统包括服务不足的少数民族人群（纳什维尔梅哈里医学院总医院）、军人人群（纳什维尔退伍军人事务医疗中心）和社区卫生系统（奥罗拉医疗中心）。

DESCRIPTION (provided by applicant): A widely-held vision arising from the Human Genome Project is use of newly available genetic information to guide preventive and therapeutic decision making in individual patients. One therapeutic area that seems particularly ripe to test this concept is pharmacogenomics, the idea that variability in therapeutic response includes a genomic component. Common variation in both germline and somatic tumor genes is an increasingly well-recognized contributor to variability in drug response, and as a result, recommendations for genotype-guided therapy are being promulgated. Through leadership in multiple genomic networks, Vanderbilt has been at the forefront of pharmacogenomic discovery and translation of this knowledge into clinical practice locally. However, few institutions or practitioners have the procedures and tools in place to incorporate genetic data into routine drug prescribing. In this proposal, we move toward this practice by establishing a program for integrating genomic medicine in diverse healthcare settings. The purpose of the Integrated, Individualized, and Intelligent Prescribing (I3P) project is to perform a multi-site demonstration that integrating genetic data within electronic health records (EHRs) can improve healthcare. We will establish the processes and infrastructure necessary to disseminate clinical genetic testing, results reporting, and decision support into diverse hospital and EHR environments. This application focuses on pharmacogenomics, given the role of adverse drug reactions (ADRs) as major causes of morbidity and mortality, the increasing number of recognized variants included in US Food and Drug Administration (FDA) labels as mediators of both efficacy and toxicity, and the relative lack of stigma attached to carriers of variants in "pharmacogenes." The project will build on two ongoing, clinical genotyping efforts at Vanderbilt: 1) the Pharmacogenomic Resource for Enhanced Decisions In Care and Treatment (PREDICT) program, which prospectively tests patients for 184 high-value germline pharmacogenomic variants including those associated with clopidogrel, warfarin and simvastatin; and 2) the Personal Cancer Medicine Initiative (PCMI), which routinely performs multiplex tumor gene mutation testing in lung cancer and melanoma to direct therapy. I3P will leverage the existing expertise, informatics, and laboratory infrastructure and resources at Vanderbilt to implement genomic medicine in three diverse healthcare systems at "early adopter" sites. These healthcare systems include underserved, minority populations (Nashville General Hospital at Meharry Medical College), military populations (Nashville Veterans Affairs Medical Center), and a community health system (Aurora Health Care).