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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.

摘要