The 1200 Patients Project: Studying Clinical Implementation of Pharmacogenomics

1200 名患者项目：研究药物基因组学的临床实施

• 批准号: 8636486
• 负责人: Peter Hugh O'Donnell
• 金额: $ 18.83万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8636486
• 关键词: Adopted; Adoption; Adult; Adverse effects; Ambulatory Care; Antineoplastic Agents; Area; Attitude; Award; Azathioprine; Behavior; Biological Models; Caring; Cause of Death; Chicago; Clinic Visits; Clinical; Clinical Pharmacology; Clinical Research; Clinical Treatment; Data; Decision Making; Direct Costs; Disease; Dose; Drug Prescriptions; Educational workshop; Effectiveness; Elements; Enrollment; Equilibrium; Event; Failure; Fellowship; Foundations; Future; Genes; Genetic; Genomics; Genotype; Goals; Grant; Habits; Health behavior; Healthcare Systems; Individual; Informal Social Control; Intervention; K-Series Research Career Programs; Knowledge; Knowledge acquisition; Laboratories; Lead; Measures; Mediating; Mediator of activation protein; Medical; Medicine; Mentors; Mentorship; Methods; Metoprolol; Modeling; Observational Study; Omeprazole; Outcome; Patients; Perception; Pharmaceutical Preparations; Pharmacogenomics; Physicians; Population; Portal System; Process; Provider; Public Health; Randomized; Reaction; Research; Research Project Grants; Resources; Risk; Role; Scientist; Shapes; Simvastatin; Social Sciences; System; Technology; Test Result; Testing; Time; Toxic effect; Training; Translations; United States; Universities; Variant; Visit; Work; Writing; base; behavior change; burden of illness; career; career development; clinical practice; clopidogrel; design; experience; genetic variant; genome wide association study; health care model; high risk; implementation research; improved; innovative technologies; interest; knowledge translation; medical specialties; novel; patient oriented research; planetary Atmosphere; programs; prospective; public health relevance; research study; response; satisfaction; theories; tool; wasting

DESCRIPTION (provided by applicant): My prior training and my immediate and long-term aspirations make this Translational Scholar Award in Pharmacogenomics and Personalized Medicine (K23) an ideal opportunity to further shape my career. Within the past three years I completed a fellowship in Clinical Pharmacology and Pharmacogenomics at the University of Chicago. My fellowship research focused on studying the pharmacogenomics of anticancer drugs. This training allowed me to develop an advanced understanding of pharmacogenomic approaches, and provided me with significant experience in designing and analyzing genome-wide association studies in pharmacogenomics. I developed and initiated two different prospective clinical observational studies with pharmacogenomic primary endpoints. These projects solidified my interest in patient-oriented research, particularly in the field of translaton of pharmacogenomics. The study of pharmacogenomics has allowed the discovery of genetic variants impacting response or toxicity for hundreds of drugs, but the information has infrequently been utilized in prescribing decisions. Implementation has been hampered by skepticism regarding the clinical utility of associations, poor physician knowledge about drug-gene relationships, limited avenues for testing, and delays in the receipt of pharmacogenomic results. I became especially interested in pursuing a clinical research project to assess whether the growing number of emerging pharmacogenomic discoveries could be used in clinical practice if common barriers to implementation could be identified and overcome. It is likely that the efficacious clinical translation of genomic discovery will be mediated by both systems/technology changes and changes in behaviors. This was the genesis for my interest in designing "The 1200 Patients Project"-the clinical research study which is the subject of this application. The study aims to determine whether and how preemptive pharmacogenomic test information might be incorporated into routine clinical treatment decisions by examining 1200 physician-patient pairs. The hypothesis is that a preemptive 'medical system model' for personalized care that makes relevant pharmacogenomic information instantaneously accessible at the time of prescribing will alter knowledge and attitudes about pharmacogenomics in ways that will improve prescribing behaviors. By providing an individualized health care model of preemptive pharmacogenomic testing, I will study how pharmacogenomic information is accessed and utilized by physicians when timely, relevant results are available; its impact on physician prescribing habits and patient and physician satisfaction with care; and the effect of physician knowledge and attitudes/perceptions about pharmacogenomics as mediators of prescribing behavior change. The proposed project is prospectively enrolling and preemptively genotyping (using a panel of variants selected for their pharmacogenomic role) 1200 adults receiving outpatient care. Patient-specific results are available to study physicians through a created research portal, or genomic prescribing system (GPS), which provides instantaneous pharmacogenomic guidance. Encounter-level data will be collected for thousands of visits to assess the aims. It is hypothesized that inappropriate or high risk medications will be less likely to be prescribed to genetically at-risk patients if pharmacogenomic results are preemptively known. In the research plan, I describe the specific methods which will be used to measure the mediators and moderators of prescribing behavior in the context of immediate availability of pharmacogenomic results. I have developed, with input from my mentors, a conceptual framework that combines elements of a dissemination and implementation model, and the self-regulation theory of health behavior. The aims are written around this model. Successful demonstration of feasibility, and refinement of the model through this study, would then justify application more widely-in diverse practice settings-in future dissemination and implementation projects. The effectiveness, future efficacy, and impact on public health will result not just from the innovative technology we employ to make pharmacogenomic information available, but from our understanding of provider-patient pair decision-making processes involved in promoting and adopting risk-reductive behavior. To be successful in this type of translational work in clinical pharmacogenomics, I need to gain specific training and experience in the areas of knowledge translation/adoption, and behavior change. I have identified new mentors with expertise in these areas to guide my Training Plan. With their direction, I have proposed a comprehensive and customized program of courses and workshops for advanced training in the social sciences and in implementation research. The University of Chicago offers a rich atmosphere of resources and mentorship in which to pursue this training and career development. With such training through this K award, I will be prepared for an independent research career in clinical implementation of pharmacogenomics. Results from the project, combined with my concomitant training, would form the foundation for my first R01 proposal in which many patient-provider pairs from diverse settings could be randomized to preemptive genotyping/GPS availability versus prescribing without pharmacogenomics, to develop more definitive evidence concerning the efficacy and effectiveness of pharmacogenomic testing on adverse drug event/response outcomes and its sustainable dissemination.

描述（由申请人提供）：我先前的培训以及我的直接和长期愿望使该译本学者奖和个性化医学（K23）成为进一步塑造我职业生涯的理想机会。在过去的三年中，我在芝加哥大学完成了临床药理学和药物基因组学研究奖学金。我的研究金研究重点是研究抗癌药物的药物基因组学。这项培训使我能够对药物基因组学方法产生深入的了解，并为我在设计和分析药物基因组学方面的全基因组关联研究方面提供了丰富的经验。我通过药物基因组主要的终点开发并启动了两种不同的前瞻性临床观察研究。这些项目巩固了我对以患者为导向的研究的兴趣，特别是在药物基因组学翻译领域。对药物基因组学的研究允许发现影响数百种药物反应或毒性的遗传变异，但是这些信息很少被用于处方决策。对联想的临床实用性，医师对药物关系的知识，测试有限的途径以及收到药物基因组成果的延迟，对实施的实施受到了阻碍。我对追求临床研究项目特别感兴趣，以评估如果可以确定并克服常见的实施障碍，是否可以在临床实践中使用越来越多的新兴药物基因组发现。基因组发现的有效临床翻译很可能是由系统/技术变化和行为变化介导的。这是我对设计“ 1200名患者项目”的兴趣 - 这是该应用程序主题的临床研究。该研究旨在通过检查1200个医生患者对，确定是否以及如何将先发制化的药物基因组学测试信息纳入常规临床治疗决策中。假设是，一种针对个性化护理的先发制人“医学系统模型”，使相关的药物基因组学信息在开处方时可以立即访问，它将以改善处方行为的方式改变对药物基因组学的知识和态度。通过提供一个个性化的先发制化药物基因组学测试的医疗保健模型，我将研究及时的医生如何访问和利用药物基因组学信息，可获得相关结果；它对医生处方习惯以及患者和医师对护理的满意的影响；以及医师知识和对药物基因组学的态度/看法作为处方行为改变的介体的影响。拟议的项目正在前瞻性地招募和预先进行基因分型（使用为其药物基因组作用选择的一组变体）1200名接受门诊护理的成年人。特定于患者的结果可通过创建的研究门户或基因组开处方系统（GPS）来研究医师，该系统提供瞬时药物基因组学指导。将收集数千次访问以评估目标的遭遇级别数据。假设不合适或高 如果有先发制人的药物基因组结果，则风险药物不太可能被遗传风险患者开处方。在研究计划中，我描述了在立即可立即获得药物基因组结果的情况下，用于测量处方行为的介体和主持人的特定方法。我通过导师的意见发展了一个概念框架，结合了传播和实施模型的要素以及健康行为的自我调节理论。目的是围绕此模型编写的。成功地证明了可行性以及通过这项研究的模型的完善，将证明应用程序在未来的传播和实施项目中更广泛地在多元化的实践设置中是合理的。不仅是我们对提供药物基因组学信息可用的创新技术的有效性，未来功效和对公共卫生的影响，还会导致我们对促进和采用降级风险行为涉及的提供者对患者的决策过程的理解。要在临床药物基因组学领域的这种转化工作中取得成功，我需要获得特定的 在知识翻译/采用和行为改变领域的培训和经验。我已经确定了在这些领域具有专业知识的新导师，以指导我的培训计划。通过他们的方向，我提出了一项全面的定制课程，包括社会科学和实施研究的高级培训的课程和讲习班。芝加哥大学提供了丰富的资源和指导氛围，可以在其中进行这项培训和职业发展。通过此K奖的这种培训，我将为药物基因组学临床实施的独立研究事业做好准备。该项目的结果以及我的随之而来的培训将为我的第一个R01提案奠定基础，其中许多来自不同环境的患者提供者可以随机分配以预先性基因分型/GPS的可用性，而没有药物基因组学，而没有药物基因组学，以开发出有关在不良药物上的效率和更确定的证据。