Balancing the Risks of Ischemia and Bleeding in Percutaneous Coronary Interventio

描述(由申请人提供)：这项赠款提案的总体目标是开发和评估一种系统，以加强对接受经皮冠状动脉介入治疗(PCI，或冠状动脉血管成形术和支架植入)的患者进行合理和个性化的抗血小板治疗。这份建议书描述了一项为期5年的研究和培训计划，旨在为候选人Robert Yeh提供必要的技能和经验，以发展在转化性心血管结果研究方面的独立学术研究生涯。候选人：叶博士拥有伦敦经济学院卫生政策硕士学位，哈佛医学院医学博士学位，并已完成内科(MGH)、心脏病学(UCSF)和介入心脏病学(MGH)的临床培训。他现在是马萨诸塞州综合医院的初级教员，有75%的保护时间进行临床研究。虽然叶博士成功地参与了流行病学和二级数据分析，但他将继续在决策分析领域进行额外的培训， 临床试验进行和实施研究，以及生物信息学培训，这将使他能够将结果研究成果转化为改善患者健康的新干预措施。候选人的长期目标是成为R01资助的研究人员，从事对人口健康具有广泛影响的应用成果研究。环境：候选人将由HMS医学副教授、哈佛临床研究所(HCRI)首席科学官Laura Mauri博士(主要导师)和HMS卫生保健政策教授、以患者为中心的结果研究所方法委员会副主席Sharon-Lise Normand博士(共同导师)指导。两者都是各自领域的国际公认的领导者，并提供与候选人的研究和培训相关的补充专业知识。Mauri博士在介入心脏病学领域成功领导改变实践的多中心临床试验，包括NIH/FDA/Industry赞助的双重抗血小板疗法(DAPT)研究方面拥有成熟的记录。她指导了几位心血管临床研究人员，包括那些获得K奖和R01资金的人。诺曼德博士成功地指导了一大批成功的学术研究人员，是本提案中使用的结果和比较有效性研究方法方面的国际公认的专家。几个哈佛医学院机构，包括HCRI、卫生保健政策部门和MGH心脏中心的联合资源，将通过教学培训、研讨会、每周研究会议和会议演示相结合的方式，为叶博士的职业发展提供丰富和富有成效的环境。研究：在当前冠状动脉疾病侵入性管理的时代，在接受冠状动脉介入治疗的患者中，平衡缺血事件和出血并发症之间的权衡已成为决定抗血小板治疗类型和持续时间的不可或缺的因素。在目标1中，多变量Logistic回归将被用来开发模型，该模型可以根据抗血小板策略，利用迄今进行的最大的经皮冠状动脉介入治疗临床试验--DAPT研究的数据，以及接受冠状动脉介入治疗的患者的综合纵向登记--马萨诸塞州经皮冠状动脉介入治疗注册中心的数据，建立预测经皮冠状动脉介入治疗后的出血和缺血事件的模型。将开发能够预测与特定策略相关的治疗益处或危害的模型。在目标2中，将使用决策分析方法来增强这些模型，以便能够为所有患者确定预测最大限度地使患者受益的治疗策略，并且可以评估这种确定中的相关不确定性。在目标3中，这些工具将被集成到一个新的软件应用程序中，该应用程序可以在MGH心导管实验室内的护理点执行多变量风险预测。这些工具将被用作临床决策辅助工具，并在一项前瞻性随机临床试验中进行测试，以确定此类干预措施是否可以提高临床决策能力。这项研究将展示如何将结果研究的最终产品转化为创新的干预措施，使医疗决策“个人化”，并最终改善患者护理。

DESCRIPTION (provided by applicant): The overall objective of this grant proposal is to develop and assess a system to enhance the rational and personalized application of antiplatelet therapy for patients undergoing percutaneous coronary intervention (PCI, or coronary angioplasty and stenting). This proposal describes a 5 year research and training program designed to provide the candidate, Robert Yeh, the necessary skills and experience to develop an independent academic research career in the conduct of translational cardiovascular outcomes research. Candidate: Dr. Yeh received an MSc in health policy from the London School of Economics, an MD from Harvard Medical School, and has completed clinical training in internal medicine (MGH), cardiology (UCSF) and interventional cardiology (MGH). He is now a junior faculty member at the Massachusetts General Hospital with 75% protected time to conduct clinical research. While he has successfully been involved with epidemiologic and secondary data analysis, Dr. Yeh will pursue additional training in the areas of decision analysis, clinical trial conduct and implementation research, and bioinformatics - training which will allow him to translate outcomes research findings into novel interventions which improve patient health. The candidate's long-term goal is to become an R01-funded investigator in the applied outcomes research that has a broad impact on population health. Environment: The candidate will be mentored by Dr. Laura Mauri (Primary Mentor), Associate Professor of Medicine at HMS and chief scientific officer of the Harvard Clinical Research Institute (HCRI), and Dr. Sharon- Lise Normand (Co-Mentor), Professor of Health Care Policy at HMS and Vice Chair of the Patient-Centered Outcomes Research Institute's Methods Committee. Both are internationally recognized leaders in their respective fields, and provide complementary expertise relevant to the research and training of the candidate. Dr. Mauri has an established track record of successfully leading practice-changing multicenter clinical trials in interventional cardiology, including the NIH/FDA/Industry-sponsored Dual Antiplatelet Theray (DAPT) Study. She has mentored several cardiovascular clinical investigators, including those that have received K awards and R01 funding. Dr. Normand has successfully mentored a large number of successful academic investigators, and is an internationally recognized expert in outcomes and comparative effectiveness research methods used in this proposal. The combined resources of several Harvard Medical School institutions, including HCRI, the Department of Health Care Policy, and the MGH Heart Center will support a rich and productive environment for Dr. Yeh's career development through a combination of didactic training, seminars, weekly research meetings, and conference presentations. Research: In the current era of invasive management of coronary artery disease, balancing the tradeoff between ischemic events and bleeding complications has become integral to decisions regarding the type and duration of antiplatelet therapy in patients undergoing coronary intervention. In Aim 1, multivariable logistic regression will be used to develop models that can predict bleeding and ischemic events in patients after PCI depending on antiplatelet strategy, using data from the DAPT Study, the largest PCI clinical trial conducted to date, and the Massachusetts PCI Registry, a comprehensive longitudinal registry of patients undergoing coronary intervention. Models that can predict treatment benefit or harm associated with specific strategies will be developed. In Aim 2, decision analysis methods will be employed to enhance these models such that the treatment strategy which is predicted to maximize patient benefit can be identified for all patients, and associated uncertainty in this determination can be assessed. In Aim 3, these tools will be integrated into a novel software application that can execute multivariable risk predictions at the point of care within the MGH cardiac catheterization laboratory. These tools will be used as clinical decision aids, and tested in a prospective randomized clinical trial to determine whether such interventions can enhance clinical decision making. The research will demonstrate how the end products of outcomes research can be translated into innovative interventions that can "personalize" medical decisions and ultimately improve patient care.