Implementing genomic medicine through pragmatic trials in diverse and underserved populations across Indiana.

通过在印第安纳州不同且服务不足的人群中进行实用试验来实施基因组医学。

• 批准号: 10820224
• 负责人: Paul Dexter
• 金额: $ 57.79万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10820224
• 关键词: APOL1 gene; Acute; Address; Administrative Supplement; Adult; Affect; African American population; African ancestry; Antidepressive Agents; Behavior; Blood Pressure; Chronic Kidney Failure; Clinical; Clinical Trials; Diagnosis; Diffusion; Foundations; Funding; Genetic Risk; Genomic medicine; Genomics; Genotype; Grant; Hypertension; Indiana; Individual; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Mental Depression; Methods; Opioid; Outcome; Pain; Participant; Patient Outcomes Assessments; Patient Recruitments; Patient-Focused Outcomes; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Pilot Projects; Population; Population Heterogeneity; Postoperative Pain; Pragmatic clinical trial; Provider; Randomized; Safety; Selection for Treatments; Test Result; Testing; Underserved Population; United States; Universities; chronic pain; clinical care; cost effective; cost effectiveness; design; disease disparity; economic impact; genetic information; genetic testing; genetic variant; health care service utilization; health difference; hypertension control; improved; method development; pharmacogenetic testing; pragmatic trial; primary endpoint; recruit; secondary analysis; secondary outcome

The IGNITE (Implementing Genomics in Practice) Consortium was created to enhance the use of genomic medicine by supporting the development of methods for incorporating genomic information into clinical care and exploration of the methods for effective implementation, diffusion and sustainability in diverse clinical settings. The IGNITE II grant was designed to establish the foundation for selected pragmatic clinical trials. As part of the network funding, the Indiana University Clinical Group is recruiting participants into both the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) and GUARDD-US (Genetic Testing to Understand and Address Renal Disease Disparities across the United States) clinical trials. GUARDD-US: This trial aims to recruit African Americans with hypertension, with or without chronic kidney disease, randomized to immediate versus delayed return of APOL1 genetic testing results. In those who are APOL1 negative, we will also conduct a pilot study to test the impact of pharmacogenetic testing on systolic blood pressure. Secondary outcomes include 6-month systolic blood pressure in chronic kidney disease patients, medications ordered, renal diagnosis and testing, patient psycho-behavioral outcomes, cost effectiveness, and the effect of pharmacogenetic-guided hypertension management on systolic blood pressure. ADOPT-PGx: This randomized pragmatic genotype-guided clinical trial tests the effect of genotype-guided therapy in three scenarios of patients: acute post-surgical pain, chronic pain, and depression. For each scenario, participants are randomized to genotype-guided drug therapy versus usual approaches to drug therapy selection. Changes in patient reported outcomes representing pain and depression control using standard PROMIS scales define the primary endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact represented by differences in healthcare utilization. The Administrative Supplement supports the continuation and conclusion of GUARDD-US and ADOPT-PGx.

IGNITE（在实践中实施基因组学）联盟的成立是为了增强基因组学的使用 通过支持开发将基因组信息纳入临床护理的方法来医学 探索在不同临床中有效实施、推广和可持续的方法 设置。 IGNITE II 拨款旨在为选定的实用临床试验奠定基础。作为 作为网络资金的一部分，印第安纳大学临床小组正在招募参与者加入 ADOPT-PGx（药物遗传学中的抑郁症和阿片类药物实用试验）和 GUARDD-US（遗传学 通过测试了解和解决美国各地肾脏疾病的差异）临床试验。 GUARDD-US：该试验旨在招募患有高血压、患有或不患有慢性肾病的非裔美国人 疾病，随机分为立即返回 APOL1 基因检测结果与延迟返回 APOL1 基因检测结果。在那些 APOL1 阴性，我们还将进行一项试点研究，以测试药物遗传学检测对收缩压的影响 血压。次要结局包括慢性肾病患者的 6 个月收缩压 患者、订购的药物、肾脏诊断和检测、患者心理行为结果、费用 有效性以及药物遗传学指导的高血压管理对收缩压的影响。 ADOPT-PGx：这项随机实用基因型指导的临床试验测试了基因型指导的效果 针对三种情况的患者进行治疗：急性术后疼痛、慢性疼痛和抑郁。对于每个 在这种情况下，参与者被随机分配接受基因型引导的药物治疗与常规药物治疗 治疗选择。患者报告结果的变化代表疼痛和抑郁控制使用 标准 PROMIS 量表定义了主要终点。二次分析包括安全终点、变化 整体福祉以及以医疗保健利用差异为代表的经济影响。 行政补充文件支持 GUARDD-US 和 ADOPT-PGx 的继续和结束。

项目成果

Recommendations for Clinical Warfarin Genotyping Allele Selection: A Report of the Association for Molecular Pathology and the College of American Pathologists.

临床华法林基因分型等位基因选择的建议：分子病理学协会和美国病理学家学会的报告。

• 发表时间: 2020
• 作者: Pratt, Victoria M;Cavallari, Larisa H;Del Tredici, Andria L;Hachad, Houda;Ji, Yuan;Kalman, Lisa V;Ly, Reynold C;Moyer, Ann M;Scott, Stuart A;Whirl;Weck, Karen E
• 通讯作者: Weck, Karen E

Development of a Genomic Data Flow Framework: Results of a Survey Administered to NIH-NHGRI IGNITE and eMERGE Consortia Participants.

基因组数据流框架的开发：对 NIH-NHGRI IGNITE 和 eMERGE 联盟参与者进行的调查结果。

• 发表时间: 2019
• 作者: Dexter, Paul;Ong, Henry;Elsey, Amanda;Bell, Gillian;Walton, Nephi;Chung, Wendy;Rasmussen, Luke;Hicks, Kevin;Owusu;Scott, Stuart;Ellis, Steve;Peterson, Josh
• 通讯作者: Peterson, Josh

Characterization of Reference Materials for TPMT and NUDT15: A GeT-RM Collaborative Project.

TPMT 和 NUDT15 参考材料的表征：GeT-RM 合作项目。

• 发表时间: 2022-10
• 作者: Pratt, Victoria M;Wang, Wendy Y;Boone, Erin C;Broeckel, Ulrich;Cody, Neal;Edelmann, Lisa;Gaedigk, Andrea;Lynnes, Ty C;Medeiros, Elizabeth B;Moyer, Ann M;Mitchell, Matthew W;Scott, Stuart A;Starostik, Petr;Turner, Amy;Kalman, Lisa V
• 通讯作者: Kalman, Lisa V

Transforming primary medical research knowledge into clinical decision.

将初级医学研究知识转化为临床决策。

• 发表时间: 2020
• 作者: Dexter, Paul R;Grout, Randall W;Embi, Peter J
• 通讯作者: Embi, Peter J

CYP2C8, CYP2C9, and CYP2C19 Characterization Using Next-Generation Sequencing and Haplotype Analysis: A GeT-RM Collaborative Project.

使用下一代测序和单倍型分析进行 CYP2C8、CYP2C9 和 CYP2C19 表征：GeT-RM 合作项目。

• 发表时间: 2022-04
• 作者: Gaedigk, Andrea;Boone, Erin C;Scherer, Steven E;Lee, Seung;Numanagić, Ibrahim;Sahinalp, Cenk;Smith, Joshua D;McGee, Sean;Radhakrishnan, Aparna;Qin, Xiang;Wang, Wendy Y;Farrow, Emily G;Gonzaludo, Nina;Halpern, Aaron L;Nickerson, Deborah
• 通讯作者: Nickerson, Deborah