Clinical Pharmacogenetics Implementation Consortium (CPIC)

 描述（由申请方提供）：遗传性基因组变异性是药物应答个体间变异性的主要原因之一。即使对于那些基因和药物，使用基因检测作为改善处方的一种工具， 药物遗传学测试在临床上还没有被迅速采用。临床药物遗传学实施联盟（CPIC）的目标是加速药物基因组学试验在临床中的正确使用。CPIC成立于2009年底，是PharmGKB和NIH药物基因组学研究网络（PGRN）之间的一个共享项目。CPIC解决了药物遗传学测试临床实施的主要障碍之一：缺乏免费提供的，同行评审的，可更新的和详细的基因/药物临床实践指南。 CPIC指南能够将基因实验室检测结果转化为针对特定药物的可操作处方决策，以基因或药物为中心。优先考虑基因/药物分组，其可采取行动的处方的证据是最强的。经过同行评审，CPIC指南同时在领先期刊上发表并发布到PharmGKB。CPIC指南的一个关键假设是，随着临床基因组检测的扩展，临床医生面临着如何使用基因检测结果的不确定性，即使他们没有明确要求对特定药物进行检测。因此，CPIC指南帮助临床医生了解如何使用现有的基因检测结果来指导处方，而不是关注是否进行基因检测。每个CPIC指南都遵循标准格式，包括哪些变体定义等位基因，等位基因的功能分配，双倍型转化为表型，处方建议（根据强度分级），支持处方建议的分级证据，全球等位基因频率以及用于临床决策支持的算法和示例语言。截至2014年8月，CPIC已发布了19个指南或更新，涵盖31种药物。这些准则被广泛引用、查阅和下载，并被主要的外部团体使用。展望未来，该资源将通过两个具体目标实现其目标。在目标1中，CPIC将继续其工作，为所有临床上可操作的基因/药物分组选择、创建和更新CPIC指南（7-14/年），并选择性地扩展指南，以包括与其他可操作基因相关的不可操作药物的明确临床建议。在目标2中，CPIC将通过持续系统地评估社区对CPIC指南的使用情况，以响应社区并根据需要进行改进，从而增强外部团体对指南的访问和输入，这些外部团体包括NIGMS的PGRN、NHGRI的基因组医学工作组、AHRQ的www.guidelines.gov、NIH的基因检测注册中心、PubMed、FDA、NHGRI的ClinGen、IOM的基因组医学圆桌会议和专业学会。除了提供临床药物基因组学社区所需的关键资源外，CPIC指南还提供了可能对基因组医学临床实施中的其他用例有用的原理方法和过程的证明。

 DESCRIPTION (provided by applicant): Inherited genomic variability is one of the major causes of inter-individual variability in drug response. Even for those genes and drugs for which there is clearly clinical utility to use genetic testing as one tool to improve prescribing, use of pharmacogenetic testing in the clinic has not been rapidly adopted. The goal of the Clinical Pharmacogenetics Implementation Consortium (CPIC) is to accelerate proper use of pharmacogenomic tests in the clinic. CPIC was formed in late 2009 as a shared project between PharmGKB and NIH's Pharmacogenomics Research Network (PGRN). CPIC addresses what has been one of the major barriers to clinical implementation of pharmacogenetic tests: the lack of freely available, peer-reviewed, updatable, and detailed gene/drug clinical practice guidelines. CPIC guidelines enable the translation of genetic laboratory test results into actionable prescribing decisions for specific drugs, centering on genes or drugs. Priority is given to gene/drug groupings for which the evidence for actionable prescribing is strongest. Following peer-review, CPIC guidelines are simultaneously published in a leading journal and posted to PharmGKB. A key assumption underlying CPIC guidelines is that as clinical genomic testing expands, clinicians are faced with uncertainty about how to use genetic test results, even if they have not explicitly ordered a test for a specific drug. Thus, CPIC guidelines help clinicians understand how to use available genetic test results to guide prescribing and do not focus on whether to order genetic tests. Each CPIC guideline adheres to a standard format that includes which variants define alleles, assignment of function to alleles, translation of diplotypes into phenotypes, prescribing recommendations (graded according to strength), graded evidence to support prescribing recommendations, allele frequencies world-wide, and algorithms and example language for clinical decision support. As of August 2014, CPIC has published 19 guidelines or updates, encompassing 31 drugs. The guidelines are widely cited, accessed, and downloaded, and are being used by leading external groups. Going forward, this resource will accomplish its goals via two specific aims. In Aim 1, CPIC will continue its work to select, create curate, and update CPIC guidelines (7-14/year) for all clinically actionable gene/drug groupings, and selectively expand the guidelines to include definitive clinical recommendations for non- actionable drugs linked to otherwise actionable genes. In Aim 2, CPIC will enhance access to and input into guidelines by external groups such as NIGMS's PGRN, NHGRI's Genomic Medicine Working group, AHRQ's www.guidelines.gov, NIH's Genetic Test Registry, PubMed, FDA, NHGRI's ClinGen, IOM's Genomic Medicine Roundtable, and professional societies by systematically evaluating community usage of CPIC guidelines on an ongoing basis to respond to the community and make enhancements as needed. Besides providing critical resources needed by the clinical pharmacogenomics community, CPIC guidelines provide proof of principle methods and processes that may be useful for other use cases in clinical implementation of genomic medicine.