Clinical Implementation Resources for Pharmacogenomics (CIRP)

7.项目总结/摘要 精准医学的成功仍然取决于我们测量基因组、环境和生物学的能力。 患者的生理状态;然后选择最大化疗效和最小化不良反应的干预措施。一个关键 精准医学的一个组成部分是了解药物基因组学（PGx）-个体间的遗传影响 药物反应变异性。美国每年发生200万起药物不良反应， 每年大约有10万人死亡，花费超过300亿美元。约15%-20%的FDA批准 药物受常见的生殖系遗传变异的影响，其有效性和安全性可以通过以下方式提高： 使用基因测试来指导处方。其中许多住院和死亡是可以预防的， 医疗机构、社区和学术医疗中心投资于基因组医学的实施， 支持PGx决策支持并返回PGx结果。10多年来，CPIC为以下方面提供了关键资源： 将患者基因型转化为针对特定药物的循证处方建议。基于这些重要的 临床指南，药物基因组学临床注释工具（PharmCAT）提供了科学和临床 社区能够用标准化的PGx调用注释原始遗传测试数据（基因型，DNA序列）， 从临床指南中获得知识，并报告随后的单倍型、双倍型和表型， 通过用户友好的软件管道提供临床指导。CPIC与PharmCAT软件相结合， 在精准医学项目中实施PGx。在这份提案中，我们概述了我们的计划， 药物基因组学临床实施资源（CIRP），以加速PGx研究的临床实施 发现。我们将通过继续制定CPIC临床指南和支持 然后由PharmCAT应用于基因检测结果的证据，用于结果翻译和随后的临床 实施PGx。CPIC（2009）和PharmCAT（2017）与PharmGKB合作的跟踪记录 （2000）在服务广泛的科学和临床社区是例外。在这一建议中，我们请求支持 推进CIRP以支持基因组知情医学，并概述一项计划，以（1）开发和利用创新的 创建、扩展和更新CPIC指南的方法（2）整合CPIC、FDA和其他公开可用的指南 通过PharmCAT指南和（3）传播PGx临床实施内容和工具，以更大的科学 本地和基于云的使用社区。

7. Project Summary/Abstract The success of precision medicine continues to rest on our ability to measure the genome, the environment, and the physiological state of patients; then choose interventions that maximize efficacy and minimize adverse effects. A key component of precision medicine is to understand pharmacogenomics (PGx) — the genetic influences on interindividual drug response variability. Two million adverse drug reactions occur annually in the United States, which results in roughly 100,000 deaths and costs upwards of $30 billion dollars each year. Approximately 15%-20% of FDA-approved medications are impacted by common germline genetic variation, and their effectiveness and safety can be improved by using genetic tests to guide prescribing. Many of these hospitalizations and deaths are preventable, prompting many health care organizations, community, and academic medical centers to invest in genomic medicine implementation by supporting PGx decision support and returning PGx results. For over 10 years, CPIC has provided critical resources to translate patient genotypes into evidence-based prescribing recommendations for specific drugs. Based on these important clinical guidelines, the Pharmacogenomics Clinical Annotation Tool (PharmCAT) provides the scientific and clinical communities the ability to annotate raw genetic test data (genotypes, DNA sequence) with standardized PGx calls, knowledge from the clinical guidelines and report the subsequent haplotypes, diplotypes and phenotypes with appropriate clinical guidance via a user-friendly software pipeline. CPIC coupled with the PharmCAT software enable the global clinical implementation of PGx in precision medicine programs. In this proposal, we outline our plan to develop the Clinical Implementation Resources for Pharmacogenomics (CIRP) to accelerate clinical implementation of PGx research discoveries. We will accomplish this plan by continuing the development of CPIC clinical guidelines and supporting evidence which are then applied to genetic test results by PharmCAT for result translation and the subsequent clinical implementation of PGx. The track record of CPIC (2009) and PharmCAT (2017) in collaboration with the PharmGKB (2000) in serving the broad scientific and clinical community is exceptional. In this proposal, we request support to advance the CIRP in support of genome-informed medicine and outline a plan to (1) develop and utilize innovative approaches to create, expand, and update CPIC guidelines (2) integrate CPIC, FDA, and other publicly available guidelines through PharmCAT and (3) disseminate PGx clinical implementation content and tools to the greater scientific community for local and cloud-based usage.