GeNYC: Genomic Implementation Research in the Diverse Settings and Populations of New York City

GeNYC：纽约市不同环境和人群的基因组实施研究

• 批准号: 10456789
• 负责人: Carol R Horowitz
• 金额: $ 35.83万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10456789
• 关键词: APOL1 gene; Address; Adult; Advocate; Affect; African ancestry; Attention; Blood Pressure; Caring; Chronic Disease; Chronic Kidney Failure; Clinic; Clinical Trials; Communities; Conduct Clinical Trials; Diabetes Mellitus; Diagnosis; Discipline; Disease Management; Educational Materials; Electronic Health Record; Equipoise; Ethics; Future; Genetic Risk; Genomic medicine; Genomics; Genotype; Health; Health Policy; Health system; Healthcare; Heart; Hypertension; Intervention; Kidney; Kidney Diseases; Kidney Failure; Latino; Low income; Medical; Medicine; New York City; Participant; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Phenotype; Plant Roots; Population; Population Heterogeneity; Positioning Attribute; Pragmatic clinical trial; Primary Health Care; Provider; Randomized; Research; Research Personnel; Risk; Science; Shapes; Site; Test Result; Testing; Training; Translational Research; Underrepresented Populations; Variant; Vulnerable Populations; Waiting Lists; Work; behavioral outcome; care providers; clinical care; clinical decision support; clinical practice; cost effectiveness; disease disparity; disorder control; disorder prevention; experience; follow-up; genetic counselor; genetic testing; health disparity; health equity; high risk; hypertensive; implementation research; implementation science; improved; innovation; literacy; meetings; patient subsets; point of care; pragmatic implementation; primary outcome; racial and ethnic; randomized trial; recruit; retention rate; risk variant; safety net; secondary outcome; support tools

The promise of genomic medicine implementation transforming healthcare and improving health will not be realized until discoveries become relevant to and available for use by diverse populations and the clinicians who care for them. Our GeNYC team is prepared to help medical genomics become an innovative, collaborative discipline with inclusiveness, health and health equity at its core. We have decades of experience engaging diverse stakeholders- researchers, patients, clinicians, advocates and entrepreneurs- to conduct chronic disease prevention and control clinical trials in our large health system and network of safety net clinics. In our 16 trials recently mean completed or underway, 80% included primary care or community sites, with a 732 participants/study, 69% were African ancestry (AA) or Latino, 17% refused, and we retained 84%. We chose toharness this expertise to conduct genomic implementation research. At the heart of our team is a Genomics Stakeholder Board. Together, we conducted GUARDD, a multi-site pragmatic clinical trial (PCT) to study effects and challenges of incorporating genetic risk information into primary care. We tested AA adults with hypertension, without diabetes or chronic kidney disease (CKD) for APOL1 high-risk variants nearly exclusive to AAs, that increase kidney failure risk 10-fold. We recruited 2052 AA adults from 15 community and academic primary care practices in NYC, trained lay staff who returned APOL1 results to patients and alerted clinicians of results through clinical decision support in electronic health records (EHRs). Our co-primary outcome, systolic blood pressure (SBP) at 3m (retention rate 93%) reduced by 6mmHg in those told they had high-risk APOL1 genotypes vs. 3mmHg if told they were low-risk (p=0.008). We are now prepared and committed to join IGNITE II and conduct genomic implementation PCTs in diverse settings and populations. We brought a transdisciplinary team together for this purpose, and to study the impact of APO1 risk information on a broader phenotype of AA patients, including those with CKD, who have even higher risk for kidney failure and are often undiagnosed by primary care providers. We aim to: (1) Serve as an enhanced diversity site for IGNITE2, facilitating recruitment and retention of patients into genomic implementation PCTs; and (2) Conduct GUARDD-US, a network-wide PCT expanding GUARDD to AA patients without and with CKD and to other IGNITE sites with different patient and provider populations. We will randomize patients to APOL1 testing vs. waitlist control, and evaluate impact on SBP, renal diagnosis, cost effectiveness and psycho-behavioral outcomes, so results can inform decisions by clinicians, policymakers and payers. If successful, GeNYC may provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices, validate APOL1 risk-informed management of hypertensive AA patients at high risk of kidney failure, contribute to important efforts to eliminate racial, ethnic and ancestral disparities in health, and show that vulnerable populations can be the first to benefit from genomic discoveries.

基因组医学实施改变医疗保健和改善健康的希望不是 意识到，直到发现与不同人群和临床医生相关并可以使用 谁在乎他们。我们的Genyc团队准备帮助医学基因组学成为一种创新， 与包容性，保健和健康平等的合作纪律是其核心。我们有数十年的经验 吸引多样化的利益相关者 - 研究人员，患者，临床医生，倡导者和企业家 - 我们的大型卫生系统和安全网络中的慢性疾病预防和控制临床试验 诊所。在我们最近的16次试验中 意思是 完成或正在进行中，有80％包括初级保健或社区网站， 732名参与者/研究，有69％是非洲血统（AA）或拉丁裔，有17％拒绝，我们保留了84％。 我们选择了这种专业知识来进行基因组实施研究。我们团队的核心 是基因组利益相关者委员会。我们一起进行了Guardd，这是一项多站点务实的临床试验（PCT） 研究将遗传风险信息纳入初级保健的效果和挑战。我们测试了AA成人 高血压，无糖尿病或慢性肾脏疾病（CKD）几乎 AAS独有的，增加肾脏衰竭的风险10倍。我们招募了来自15个社区的2052年AA成年人， 纽约市的学术初级保健实践，经过培训的外行员工，他们将APOL1结果退还给患者并提醒 通过电子健康记录（EHRS）中的临床决策支持，结果临床医生。我们的共同主要 结果，在3M（保留率为93％）的收缩压（SBP）降低了6mmhg，其中这些人已经知道他们已经 高风险的APOL1基因型与3mmHg如果被告知它们是低风险的（P = 0.008）。 我们现在已准备好并致力于加入IGNITE II并进行基因组实施PCT 不同的环境和人口。为此，我们将一个跨学科团队聚集在一起，并学习 APO1风险信息对AA患者的更广泛表型的影响，包括患有CKD的患者 肾功能衰竭的风险甚至更高，并且经常被初级保健提供者未诊断。我们的目标是：（1） 充当Ingite2的增强多样性站点，促进招募并将患者保留到基因组中 实施PCT； （2）执行Guardd-Us，一个网络范围的PCT，将后卫扩展到AA 没有CKD的患者以及其他患者和提供者人群的点火场所。我们将 将患者随机进行APOL1测试与候补名单控制，并评估对SBP，肾脏诊断，成本的影响 有效性和心理行为结果，因此结果可以为临床医生，决策者和政策制定者的决定提供信息 付款人。如果成功，genyc可能会为将来的努力提供一个强大的框架来实施基因组 在各种临床实践中的医学，验证APOL1高血压AA患者的风险风险管理 在肾脏衰竭的高风险中，为消除种族，种族和祖先差异的重要努力做出了贡献 健康，并表明脆弱人群可能是第一个从基因组发现中受益的人。