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。

基本信息

批准号：
9929348
负责人：
Paul Dexter
金额：
$ 240.37万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
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/9929348
关键词：
Accreditation Acute Pain Adoption Adverse effects Adverse event Affect Alleles American Area 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 Genetic screening method 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 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

项目摘要

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) 招募少数族裔和服务不足的患者参加 IGNITE II 实用临床试验（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不良事件。印第安纳大学和当前的研究人员此前已经开展了研究用于有效招募来自不同临床环境的研究参与者的基础设施和协议印第安纳州。全州地理编码的电子医疗记录和社区相关数据使我们能够识别并招募少数族裔研究参与者和居住在联邦指定服务欠缺地区的人。在通过与我们的医疗机构合作伙伴协调，我们的多学科团队非常适合申请从 IGNITE I 中汲取的经验教训来实施广泛的基因组医学方案，有助于网络范围内的分析，与其他临床小组合作，并帮助影响基因组临床实践和政策。认识到阿片类药物处方的滥用已成为一场国家危机，我们提出一项 PCT 药物遗传学指导的阿片类药物选择和剂量，旨在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。印第安纳州的人均阿片类药物处方量在全国排名第九在服药过量死亡人数中排名第 17 位。印第安纳州的农村和医疗服务匮乏的地区是最缺乏的地区之一做作的。然而，尽管存在相关风险，阿片类药物对于治疗许多严重的病例仍然具有无价的价值。疼痛。最常用的阿片类药物（羟考酮、氢可酮、可待因或曲马多）被转换通过肝酶 CYP2D6 转化为具有药理活性的代谢物。然而，近 10% 的患者编码极低或极高 CYP2D6 活性的等位基因，需要改变阿片类药物剂量或选择。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疗法，只有极少数诊所实施。利用我们在阿片类药物遗传学方面的专业知识以及我们建议能够识别印第安纳州的阿片类药物处方并进行临床 CYP2D6 基因分型 OPTIMIZE 研究（阿片类药物遗传学指导的治疗实施以最大化疗效）务实的、前瞻性的、随机的临床试验，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毒性。使用聚类随机化研究设计（按诊所），研究参与者 (n=1333) 将被纳入两个研究组之一，CYP2D6- 指导阿片类药物的选择和剂量（干预）或护理标准（控制）。我们将招募以下人员 (1) 安排进行通常需要术后阿片类药物的手术，或 (2) 开具 CYP2D6- 代谢阿片类药物，有证据表明阿片类药物剂量不断增加导致慢性疼痛不受控制。基本的结果将是自我报告的疼痛控制和阿片类药物相关的不良事件。我们期望向提供者提供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。