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: 9982391
• 负责人: Carol R Horowitz
• 金额: $ 305.42万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982391
• 关键词: APOL1 gene; Address; Adult; Advocate; Affect; African; 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; 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 Groups; Variant; Vulnerable Populations; Waiting Lists; Work; behavioral outcome; care providers; clinical care; clinical decision support; clinical practice; cost effectiveness; disorder control; disorder prevention; experience; follow-up; genetic counselor; genetic testing; health disparity; health equity; high risk; implementation research; implementation science; improved; innovation; literacy; meetings; patient subsets; point of care; 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.

基因组医学的实施改变医疗保健和改善健康的承诺将不会被 直到发现与不同人群和临床医生相关并可供其使用 谁照顾他们。我们的GeNYC团队准备帮助医学基因组学成为一个创新的， 以包容性、健康和健康公平为核心的协作学科。我们有几十年的经验 让不同的利益相关者--研究人员、患者、临床医生、倡导者和企业家--参与 慢性病防治临床试验是我国大卫生体系的安全网 诊所。在我们最近的16次试验中 是说 已完成或正在进行中，80%包括初级保健或社区网站， 732名参与者/研究，69%是非洲血统（AA）或拉丁美洲人，17%拒绝，我们保留了84%。 我们选择利用这一专业知识进行基因组实施研究。在我们团队的核心 是一个基因组利益相关者委员会。我们一起进行了GUARDD，一项多中心实用临床试验（PCT） 研究将遗传风险信息纳入初级保健的影响和挑战。我们测试了戒酒会的成年人 有高血压、无糖尿病或慢性肾脏病（CKD）者为APOL 1高危变异近 仅限于AA，这会增加10倍的肾衰竭风险。我们从15个社区招募了2052名AA成年人， 在纽约市的学术初级保健实践中，培训了非专业人员，他们将APOL 1结果返回给患者，并提醒 通过电子健康记录（EHR）中的临床决策支持，临床医生可以了解结果。我们的合作伙伴 结果，3个月时收缩压（SBP）（留存率93%）下降6 mmHg， 高风险APOL 1基因型与3 mmHg，如果告诉他们是低风险（p=0.008）。 我们现在已经准备好并致力于加入IGNITE II，并在2020年进行基因组实施PCT。 不同的环境和人口。为此，我们召集了一个跨学科的团队， APO 1风险信息对AA患者更广泛表型的影响，包括CKD患者， 患肾衰竭的风险更高，而且往往得不到初级保健提供者的诊断。我们的目标是：（1） 作为IGNITE 2的增强多样性位点，促进患者的招募和保留， 实施过程控制技术;以及（2）开展GUARDD-US，这是一个将GUARDD扩展为AA的全网络PCT 非CKD患者和CKD患者，以及其他IGNITE研究中心的不同患者和提供者人群。我们将 将患者随机分配至APOL 1检测组与等待名单对照组，并评价对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，政策制定者和 付款人。如果成功的话，GeNYC可能会为未来实现基因组学的努力提供一个强大的框架。 药物在不同的临床实践中，验证高血压AA患者的APOL 1风险知情管理 肾衰竭的高风险，有助于消除种族，民族和祖先的差异， 健康，并表明弱势群体可以首先从基因组发现中受益。