Novel Approaches to Monitor the Safety and Effectiveness of Newly Marketed Diabetes Medications in Older Adults Considering Frailty and Multimorbidity

本申请书为临床科学家导师研究职业发展奖(K08)，由 Elisabetta Patorno，医学博士，DrPH对PA-16-191的反应。帕托诺医生是一名预防医学医生， 布里格姆妇女医院药物流行病学部的药物流行病学家 哈佛医学院医学助理教授。随着美国人口的迅速增长，≥65 年，谁使用的药物比例最大，更好地了解药物的影响 在常规护理中使用的老年人是当务之急。这种需求对新药的需求甚至更加迫切，通常 根据相对较小、较短且通常是安慰剂对照的随机证据进入市场 试验(RCT)，在这些试验中，老年患者的代表性往往不足或被排除在外。因此，临床医生经常 努力为他们的老年患者选择最好的治疗方法，特别是那些虚弱和多发病的患者。 帕托诺博士致力于作为一名独立的临床研究员的职业生涯，专注于推动 对在常规护理中治疗的老年人的药物效果进行严格监测的研究。 为了实现这一目标，帕托诺博士提出了一个为期4年的职业发展和指导性研究计划 以开发有效的系统为中心，及时和高质量地提供新的糖尿病证据 专门针对老年患者护理的独特方面而量身定做的老年患者药物 如虚弱和多发病。这种研究环境结合了对信息的迫切需求 FDA在过去十年中批准的10多种新降糖药的效果，需要 开发在现实世界老年人中进行前瞻性药物监测的新方法。在高度发达的 药物流行病学部富有成效和支持性的研究环境，帕托诺博士将 与来自哈佛各机构的导师和合作者组成的跨学科团队合作 在以下具体实质性领域拥有深厚专业知识和国内/国际声誉的大学 她提议的培训：临床老年病学和糖尿病，前瞻性监测和数据挖掘的方法， 以及老年人口中的健康服务研究。她指导的研究的首要目标是 创建和实施一种新的方法，用于近乎实时地监测相对安全性和 新的糖尿病药物在老年患者常规护理中的有效性。这种新型的监控 该方法将使用相对较短的滞后时间可用的联邦医疗保险索赔数据，与电子医疗相关联 记录和联邦医疗保险当前受益人调查。拟议的工作将提供及时和可操作的 临床医生治疗老年人的知识，定义新抗糖尿病药物的净增量价值 年长的患者虚弱和多发病。从这项工作中获得的知识将影响数百万人 在美国的老年人，并将为申请人提供成为独立的坚实的背景 研究人员，并最终成为老龄人口用药和结果研究的领导者。

This application for a Mentored Clinical Scientist Research Career Development Award (K08) is submitted by Elisabetta Patorno, MD, DrPH in response to PA-16-191. Dr. Patorno is a preventive medicine physician and pharmacoepidemiologist in the Division of Pharmacoepidemiology at Brigham and Women's Hospital, and Assistant Professor of Medicine at Harvard Medical School. With a rapidly increasing US population ≥ 65 years, who use the largest proportion of medications, a better understanding of the effects of medications in older adults as used in routine care is imperative. This need is even more acute for new drugs that usually enter the market on the basis of evidence from relatively small, short, and often placebo-controlled randomized trials (RCTs), in which older patients are often underrepresented or excluded. As a result, clinicians often struggle choosing the best treatment for their older patients, particularly those with frailty and multimorbidity. Dr. Patorno is committed to a career as an independent clinical investigator, focused on advancing research for rigorously monitoring the effects of medications in older adults as treated in routine care. To achieve this, Dr. Patorno proposes a 4-year program of career development and mentored research centered on the development of a valid system for timely and high-quality evidence on new diabetes drugs in older patients specifically tailored to address the unique aspects of care in older patients such as frailty and multimorbidity. This setting of research combines the urgent need for information on the effects of over 10 new antidiabetic agents approved by the FDA in the last decade with the need for the development of novel methods for prospective drug monitoring in real-world older adults. Within the highly productive and supportive research environment of the Division of Pharmacoepidemiology, Dr. Patorno will work with an interdisciplinary team of mentors and collaborators drawn from across institutions at Harvard University that have deep expertise and national/international reputations in the specific substantive areas of her proposed training: clinical geriatrics and diabetology, methods for prospective monitoring and data mining, and health services research in older populations. The overarching objective of her mentored research is to create and implement a novel approach for the near-real-time monitoring of the comparative safety and effectiveness of new diabetes drugs in older patients as treated in routine care. This novel monitoring approach will use Medicare claims data available with a relatively short lag time, linked to electronic medical records and the Medicare Current Beneficiary Survey. The proposed work will provide timely and actionable knowledge for clinicians treating older adults, defining the net incremental value of new antidiabetic agents in older patients with frailty and multimorbidity. The knowledge gained from this work will impact several million older adults in the US, and will provide the applicant with a solid background to become an independent researcher, and ultimately a leader, in the study of medication use and outcomes in aging populations.