Clinical Implementation Resources for Pharmacogenomics (CIRP)

7.项目摘要/摘要 精确医学的成功仍然取决于我们测量基因组、环境和 患者的生理状态；然后选择最大限度提高疗效和最大限度减少不良反应的干预措施。一把钥匙 精确医学的组成部分是理解药物基因组学(PGx)--遗传对个体间的影响 药物反应的可变性。美国每年发生200万例药物不良反应，导致 每年约有10万人死亡，造成超过300亿美元的损失。FDA批准的约15%-20% 药物会受到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。这些住院和死亡中的许多是可以预防的，促使许多人 关怀组织、社区和学术医疗中心通过以下方式投资于基因组医学实施 支持PGx决策支持和返回PGx结果。10多年来，CPIC为 将患者的基因分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 社区能够使用标准化的PGx呼叫来注释原始基因测试数据(基因类型、DNA序列)， 从临床指南中了解并报告后续的单倍型、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，使全球 PGx在精准医学项目中的临床应用。在这项建议中，我们概述了我们的计划，以发展 药物基因组学(CIRP)的临床实施资源加速PGx研究的临床实施 发现。我们将通过继续开发CPIC临床指南和支持来完成这一计划 证据，然后由PharmCAT应用于基因测试结果，以进行结果转换和随后的临床 Pgx的实现。CPIC(2009)和PharmCAT(2017)与PharmGKB合作的跟踪记录 (2000)在为广大科学和临床社区服务方面是例外的。在这项提案中，我们请求支持 推进支持基因组信息医学的CIRP，并概述计划：(1)开发和利用创新 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 通过PharmCAT和(3)向更多的科学工作者传播PGx临床实施的内容和工具 用于本地和基于云的使用的社区。

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.