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: 10188586
• 负责人: Paul Dexter
• 金额: $ 79.34万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188586
• 关键词: Accreditation; Acute Pain; Adoption; Adverse effects; Adverse event; Affect; Alleles; American; Biometry; CLIA certified; CYP2D6 gene; Caring; Clinic; Clinical; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Codeine; Communities; Consult; Data; Decision Support Systems; Disease; Distress; Dose; Economics; Effectiveness; Electronic Health Record; Emergency Situation; Enrollment; Enzymes; Genes; Genetic; Genomic medicine; Genomics; Genotype; Goals; Guidelines; Health; Healthcare; Healthcare Systems; Hydrocodone; Indiana; Individual; Institutes; Intervention; Laboratories; Learning; Liver; Medical; Medically Underserved Area; Minority; Minority Recruitment; Operative Surgical Procedures; Opiate Addiction; Opioid; Opioid Analgesics; Oxycodone; Pain; Pain interference; Pain management; Participant; Patient Self-Report; Patients; Pharmacodynamics; Pharmacogenetics; Pharmacology; Phase; Policies; Policy Maker; Population; Population Heterogeneity; Positioning Attribute; Postoperative Period; Pragmatic clinical trial; Productivity; Protocols documentation; Provider; Randomized; Randomized Clinical Trials; Recommendation; Recording of previous events; Reporting; Research; Research Design; Research Infrastructure; Research Methodology; Research Personnel; Risk; Safety; Schedule; Services; Severities; Site; Testing; Toxic effect; Tramadol; Underserved Population; United States Health Resources and Services Administration; Universities; addiction; base; biomedical informatics; chronic pain; clinical practice; economic outcome; genetic association; genetic testing; genetic variant; health care availability; healthcare community; improved; improved outcome; inclusion criteria; interest; medical specialties; multidisciplinary; opioid abuse; opioid overdose; opioid therapy; opioid use; overdose death; pain reduction; pragmatic trial; prescription opioid; prescription opioid abuse; primary outcome; prospective; recruit; research study; response; rural underserved; secondary outcome; standard of care; success; two-arm study; underserved area

The goals of this project are 1) to recruit minority and underserved patients to the IGNITE II pragmatic clinical trials (PCT) network; and 2) to test the effects of genotype-guided opioid therapy on pain control and opioid- related adverse events. Indiana University and the current investigators have previously developed research infrastructure and protocols for efficiently recruiting study participants from diverse clinical settings across Indiana. State-wide geocoded electronic health care records and community-related data allow us to identify and recruit minority study participants and those who live in federally-designated underserved areas. In coordination with our healthcare institutional partners, our multi-disciplinary team is ideally positioned to apply lessons learned from IGNITE I to implement a wide range of genomic medicine protocols, contribute to network-wide analyses, collaborate with other clinical groups, and help influence genomic clinical practice and policy. Recognizing that abuse of opioid prescriptions has become a national crisis, we propose a PCT of pharmacogenetic-guided opioid selection and dosing with a goal of optimizing pain control and increasing the safety of using opioids in clinical practice. Indiana is 9th in the nation in terms of opioid prescriptions per capita and 17th in overdose deaths. Rural and medically underserved areas found in Indiana are amongst the most affected. Despite the associated risks, however, opioids are still invaluable to managing many cases of severe pain. The most commonly prescribed opioids (oxycodone, hydrocodone, codeine, or tramadol) are converted to pharmacologically active metabolites by the liver enzyme, CYP2D6. However, nearly 10% of patients have alleles encoding either extremely low or extremely high CYP2D6 activity, warranting altered opioid dosing or selection. Despite strong evidence and clinical guidelines for using CYP2D6 genetic testing to guide opioid therapy, it is implemented in very few clinics. Leveraging our expertise in opioid pharmacogenetics, as well as the ability to identify opioid prescriptions across Indiana and perform clinical CYP2D6 genotyping, we propose the OPTIMIZE study (Opioid Pharmacogenetics-guided Therapy Implementation to MaximIZe Effectiveness), a pragmatic, prospective, randomized, clinical trial designed to test the hypothesis that implementing CYP2D6 genotyping improves opioid effectiveness and reduces associated toxicities. Using a cluster randomization study design (by clinic), study participants (n=1333) will be enrolled into one of two study arms, CYP2D6- guided opioid selection and dosing (intervention) or standard of care (control). We will recruit individuals who are either (1) scheduled for surgeries typically requiring post-operative opioids, or (2) prescribed a CYP2D6- metabolized opioid with evidence of uncontrolled chronic pain based on escalating opioid dose. Primary outcomes will be self-reported pain control and opioid-related adverse events. We expect the pharmacogenetic recommendations given to the provider will improve these outcomes, and consequently reduce the risks associated with opioid treatment.

该项目的目标是1）招募少数群体和服务不足的患者到INGITE II务实的临床 试验（PCT）网络； 2）测试基因型引导的阿片类药物治疗对疼痛控制和阿片类药物的影响 相关的不良事件。印第安纳大学和现任研究人员以前已经开发了研究 用于有效招募研究参与者的基础设施和方案 印第安纳州。全州地理编码的电子医疗保健记录和与社区有关的数据使我们能够识别 并招募少数群体研究参与者以及居住在联邦指定的未服务不足的地区的参与者。在 与我们的医疗机构合作伙伴的协调，我们的多学科团队是理想的申请 从Ignite I中学到的经验教训以实施广泛的基因组医学方案，有助于 网络范围内的分析，与其他临床组合作，并有助于影响基因组临床实践和 政策。认识到滥用阿片类药物处方已成为一场国家危机，我们提出了一个PCT 药物遗传学引导的阿片类药物选择和给药，目的是优化疼痛控制并增加 在临床实践中使用阿片类药物的安全性。在人均处方方面，印第安纳州在全国排名第9 和过量死亡的第17名。在印第安纳州发现的农村和医疗服务不足的地区是最多的 做作的。尽管有相关的风险 疼痛。最常见的阿片类药物（羟考酮，氢可酮，可待因或曲马多）已转换 通过肝酶CYP2D6进行药理学活性代谢产物。但是，将近10％的患者患有 编码极低或极高的CYP2D6活性的等位基因，需要改变阿片类药物的剂量或 选择。尽管有强有力的证据和临床指南使用CYP2D6基因检测来指导阿片类药物 治疗，它是在很少的诊所中实施的。利用我们在阿片类药物遗传学方面的专业知识以及 鉴定印第安纳州各地阿片类药物处方并进行临床CYP2D6基因分型的能力，我们提出 优化研究（阿片类药物遗传学引导的治疗实施以最大化有效性） 务实，前瞻性，随机，临床试验旨在检验实施CYP2D6的假设 基因分型可提高阿片类药物的有效性并降低相关的毒性。使用群集随机化 研究设计（由诊所），研究参与者（n = 1333）将招募到两个研究组之一，CYP2D6- 指导阿片类药物的选择和给药（干预）或护理标准（对照）。我们将招募个人 要么（1）计划进行通常需要术后阿片类药物的手术，要么（2）规定了CYP2D6-- 代谢阿片类药物具有基于阿片类药物剂量不断升级的慢性疼痛的证据。基本的 结果将是自我报告的疼痛控制和与阿片类药物有关的不良事件。我们期望 提供给提供者的药物遗传学建议将改善这些结果，因此 降低与阿片类药物治疗相关的风险。