Better Outcomes for Children: Promoting Excellence in Healthcare Genomics to Inform Policy

 描述（由申请人提供）：2012年5月，辛辛那提儿童（CCHMC）与我们的波士顿儿童合作伙伴一起加入eMERGE II。从那时起，我们开发了电子健康记录（EHR）的算法，领导了儿科工作组，开发了药物基因组学，评估了父母和护理人员对推进基因组医学的偏好，并将技术进步融入了我们的EHR。eMERGE努力已成为机构倡议的基本结构，以纳入遗传学，基因组学和生物学的非凡进步。 将电子病历引入医疗保健。此外，我们还带来了一个全面的EHR（EPIC），在CCHMC的每个医疗保健提供场所运行;一个包含120万条患者记录的去识别i2 b2数据仓库;以及一个拥有150，000份同意书的生物银行，允许向38，000名患者和监护人返回结果，他们提供了58，000份DNA样本，所有这些都同意返回结果和i2 b2 EHR记录。现在，我们提出了我们加入eMERGE III网络的计划，其中包括17项拟议举措。我们的eMERGE努力旨在与我们的eMERGE III合作伙伴一起将整个机构带入医疗保健实施和发现的基因组EHR时代。我们的工作分为基因组学，目标1，我们希望帮助eMERGE III指导委员会为eMERGE III靶向基因组（eTGP）确定100个左右的基因，选择我们的2,000名CCHMC患者进行测序（我们生物库中的38,000个），审查CCHMC临床护理中的4,000个靶向基因组，以进行体细胞镶嵌和重新解释，并进一步开发和推广序列分析软件工作流程套件（CASSI）。对于表型，目标2，我们将扩展我们的工作，使用启发式和机器学习方法生成EHR表型算法，并使用来自数据驱动算法的一组全面的EHR特征来描述eTGP基因变体的表型多效性。我们将通过将eMERGE开发的EHR算法应用于这些大型电子数据仓库，与患者护理成果研究所（PCRI）和百万退伍军人计划开展工作合作。对于实施和评价，目标3，我们将开发工具来评价青少年返回结果的偏好，检查伦理和法律的义务和潜力，重新分析结果，分析他克莫司管理的肾移植的成本与不CYP 3A 5检测，开发临床决策支持表型，测试排序，并返回eTGP结果。我们在这些eMERGE III研究中的成功将通过对CCHMC生物银行，综合EHR（EPIC）和i2 b2去识别医疗记录数据仓库的持续机构投资以及数百名使基因组学或信息学成为其研究重点的教师和高级工作人员来加强。我们提出了一个全面的计划，解决了eMERGE III（HG-14-025）RFP中提出的所有突出元素，以提高我们在eMERGE网络中的协作生产力，最终通过发现，实施和基因组学和信息学的高级应用来改善我们的医疗保健系统。

 DESCRIPTION (provided by applicant): In May 2012 Cincinnati Children's (CCHMC) joined eMERGE II with our Boston Children's partner. Since then we have developed algorithms for the electronic health record (EHR), led the Pediatric Workgroup, developed pharmacogenomics, evaluated the preferences of parents and caregivers to advance genomic medicine and assimilated technical advances into our EHR. The eMERGE effort has become the basic fabric of the institutional initiative to incorporate the extraordinary advances of genetics, genomics and the electronic medical record into healthcare. In addition, we bring a comprehensive EHR (EPIC), operating in every venue for healthcare delivery at CCHMC; a deidentified i2b2 data warehouse of 1.2 million patient records; and a Biobank with 150,000 consents that allow return of results to 38,000 patients and guardians who have provided 58,000 DNA samples, all with consent to return results and i2b2 EHR records. Now, we present our plan to join the eMERGE III network with 17 proposed initiatives. Our eMERGE effort is designed to move an entire institution with our eMERGE III partners into a genomic-EHR era of healthcare implementation and discovery. Our effort is divided into Genomics , Aim 1, where we hope to help the eMERGE III Steering Committee identify the 100 or so genes for the eMERGE III Targeted Gene Panel (eTGP), select our 2,000 CCHMC patients to be sequenced (of the 38,000 in our Biobank), review 4,000 targeted gene panels from clinical care at CCHMC for somatic mosaicism and reinterpretation, and further develop and disseminate a software workflow suite for sequence analysis (CASSI). For Phenotypes, Aim 2, we will extend our work generating EHR phenotype algorithms using heuristic and machine learning methods with a comprehensive set of EHR features derived from data driven algorithms to describe phenotypic pleiotropy of eTGP gene variants. We will develop working collaborations with Patients Care Outcomes Research Institute (PCORI) and the Million Veterans Program by applying eMERGE developed EHR algorithms to these large electronic data warehouses. For Implementation and Evaluation, Aim 3, we will develop tools to evaluate adolescent return of results preferences, examine the ethical and legal obligations and potential to reanalyze results, analyze the cost of tacrolimus management of kidney transplant with and without CYP3A5 testing, develop clinical decision support for phenotyping, test ordering, and returning eTGP results. Our success in these eMERGE III studies will be enhanced by the ongoing institutional investments made in the CCHMC BioBank, the comprehensive EHR (EPIC), and the i2b2 deidentified medical record data warehouse, and hundreds of Faculty and senior staff who make genomics or informatics an active focus of their research. We present a comprehensive program addressing all of the salient elements presented in the RFP for eMERGE III (HG-14-025) to enhance our collaborative productivity within the eMERGE Network in ways that ultimately improve our healthcare systems through discovery, implementation, and advanced applications of genomics and informatics.