Sparking Advancements in Genomic Medicine

激发基因组医学的进步

基本信息

批准号：
9789905
负责人：
JULIE A. JOHNSON
金额：
$ 36.74万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-16 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9789905
关键词：
Acute Acute Pain Address Adult Affect American Analgesics CYP2D6 gene Cessation of life Child Health Childhood Clinical Codeine Cost Effectiveness Analysis Cytochrome P450 Data Data Collection Data Reporting Delaware Drug Interactions Drug usage Enrollment Enzymes Florida Funding Generations Genetic Diseases Genetic Polymorphism Genomic medicine Genotype Health Health Care Costs Health system Heart Diseases Hospitalization Hydrocodone Lead Leadership Legal Lung diseases Malignant Childhood Neoplasm Malignant Neoplasms Measures Medicare/Medicaid Metabolism Minority Operative Surgical Procedures Opiate Addiction Opioid Oxycodone Pain Pain intensity Pain management Patient Care Patient Outcomes Assessments Patients Perception Personal Satisfaction Pharmaceutical Preparations Pharmacogenetics Pharmacotherapy Phenotype Physicians Population Population Heterogeneity Pragmatic clinical trial Primary Health Care Proteins Randomized Recommendation Replacement Arthroplasty Resources Risk Role Schedule II opioids Societies Surveys Testing Toxic effect Tramadol United States National Institutes of Health Ursidae Family addiction base cancer pain chronic pain clinical practice community setting cost cost effective cost effectiveness experience genetic information health care service utilization improved inhibitor/antagonist loss of function medically underserved neonate non-opioid analgesic opioid epidemic opioid misuse opioid use prescription opioid public health emergency response stem tool treatment as usual

项目摘要

Abstract More Americans suffer from acute or chronic pain each year than are affected by heart disease, cancer and lung disease, and opioids represent the cornerstone of pain management. Prescriptions for opioids have tripled since 1999, paralleled by increases in opioid-related hospitalizations and deaths, and contributing importantly to the opioid epidemic. Hydrocodone, tramadol, and codeine are among the most commonly prescribed opioids, and the cytochrome P450 enzyme, CYP2D6, is central to generation of highly potent metabolites for these opioids. CYP2D6 has common genetic polymorphisms that lead to loss of function, reduced function, or increased function, conferring poor (PM), intermediate (IM), and ultrarapid (UM) metabolism phenotypes, respectively. Data suggest these three opioids should be avoided in PMs, IMs and UMs due to increased risk for poor response and toxicity, respectively. Leveraging our data from IGNITE-I, extensive stakeholder engagement, and to address the significant burden of both pain and opioid use in the U.S., we propose to test the hypothesis that CYP2D6 genotype-guided pain management leads to improved patient reported outcomes (PRO) for pain control and is cost-effective in a real-world setting. We propose a multicenter pragmatic clinical trial (PCT) of 2,100 patients with acute and chronic pain, randomized 2:1 to a genotype-guided versus usual care approach. We will enroll adults and children with cancer pain or at least 3 months of poorly controlled chronic pain and those undergoing total joint arthroplasty. Considering CYP2D6 genotype and relevant CYP2D6 inhibitor drug interactions, patients categorized as PM, IM, or UM will have a recommendation to avoid hydrocodone, tramadol and codeine. In those categorized as NM, use of tramadol will be preferred, as tramadol has lower risk of addiction than DEA Schedule II opioids. Our primary hypothesis of improved pain control with a genotype-guided strategy will be tested based on PRO of pain intensity using NIH PROMIS measures. We will utilize a multi-gene pharmacogenetic panel and also make recommendations on other drugs with established pharmacogenetic guidance. Our secondary hypothesis is that use of a pharmacogenetic panel to guide opioids and other commonly used drugs will improve patient wellbeing and reduce healthcare utilization. We will utilize validated PRO tools to assess wellbeing. Healthcare utilization and cost effectiveness analyses will be based on claims data from Medicare and Medicaid, supplemented with patient reported data on cost drivers for acute/chronic pain. We will also test physician perception of the benefit of a pharmacogenetic-guided approach to patient care. With these endpoints we can address the potential benefits of a genotype-guided approach to drug therapy that focuses on numerous stakeholders, including patients, the physicians who treat them, health systems/payers and society, relative to concerns about opioid use and addiction. To conduct this and other IGNITE-II PCTs we have assembled an outstanding team called the UF-Nemours Clinical Group, which brings to bear exceptional clinical resources.

抽象的每年的美国人每年遭受急性或慢性疼痛的痛苦比受心脏病，癌症和肺部疾病和阿片类药物代表疼痛管理的基石。阿片类药物的处方自1999年以来的两倍，与阿片类药物相关的住院和死亡的增加以及贡献重要的是阿片类药物流行。氢可酮，曲马多和可待因是最常见的处方的阿片类药物和细胞色素P450酶CYP2D6是高度有效的核心这些阿片类药物的代谢物。 CYP2D6具有常见的遗传多态性，导致功能丧失，功能降低或功能提高，赋予较差（PM），中级（IM）和超级（UM）代谢表型分别。数据表明，应在PM，IMS和 UMS由于反应不良和毒性的风险增加而引起的。利用我们的数据从ignite-i，广泛的利益相关者参与，并应对疼痛和阿片类药物使用的重大负担美国，我们建议检验以下假设：CYP2D6基因型引导的疼痛管理可改善患者报告的疼痛控制结果（PRO），在现实环境中具有成本效益。我们提出了一个 2100例急性和慢性疼痛患者的多中心务实临床试验（PCT）随机2：1 基因型引导与通常的护理方法。我们将入学癌症疼痛或至少3个慢性疼痛和经历总关节性置换术的人数数月。考虑CYP2D6 基因型和相关的CYP2D6抑制剂药物相互作用，归类为PM，IM或UM的患者将具有建议避免氢可酮，曲马多和可待因。在分类为NM的那些中，使用曲马多将是首选，因为曲马多的成瘾风险低于DEA附表II阿片类药物。我们的主要通过基因型引导的策略改善疼痛控制的假设将根据疼痛的pro进行测试使用NIH Promis度量的强度。我们将使用一个多基因药物遗传学面板，也可以使对其他具有既定药物遗传学指导的药物的建议。我们的第二个假设是使用药物遗传学面板指导阿片类药物和其他常用药物将改善患者福祉并减少医疗保健利用。我们将利用经过验证的Pro工具来评估健康。卫生保健利用和成本效益分析将基于Medicare和Medicaid的索赔数据，补充患者报告了有关急性/慢性疼痛的成本驱动因素的数据。我们还将测试医生对患者护理的药物遗传学指导方法的感知。使用这些终点，我们可以解决了基因型引导的药物治疗方法的潜在好处，该方法侧重于众多利益相关者，包括患者，对待他们的医生，卫生系统/付款人和社会，相对于对阿片类药物使用和成瘾的关注。为了进行此和其他IGNITE-II PCT，我们已经组装了杰出的团队称为UF-Nemours临床集团，这带来了出色的临床资源。