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

考虑到虚弱和多重疾病，监测新上市糖尿病药物对老年人的安全性和有效性的新方法

• 批准号: 10066296
• 负责人: Elisabetta Patorno
• 金额: $ 16.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066296
• 关键词: Acute; Address; Adverse event; Aging; Antidiabetic Drugs; Area; Cardiovascular system; Caring; Clinical; Clinical Investigator; Computerized Medical Record; Data; Decision Making; Development; Diabetes Mellitus; Drug Monitoring; Effectiveness; Elderly; Environment; Epidemic; Event; Exposure to; FDA approved; Geriatrics; Glucose; Health Services Research; Health Status; Healthcare; Hospitals; Hypoglycemia; Individual; Infrastructure; Institution; Institutionalization; International; Investigation; K-Series Research Career Programs; Knowledge; Link; Marketing; Mediator of activation protein; Medicare; Medicare claim; Medicine; Mentors; Methods; Mission; Modeling; Monitor; National Institute on Aging; Older Population; Outcome; Patients; Pattern; Periodicals; Pharmaceutical Preparations; Pharmacoepidemiology; Physicians; Polypharmacy; Population; Preventive Medicine; Production; Registries; Research; Research Personnel; Residual state; Risk; Safety; Scanning; Scientist; Signal Transduction; Solid; Surveys; System; Techniques; Test Result; Time; Training; Trees; Universities; Woman; Work; base; beneficiary; career; career development; cohort; comorbidity; comparative effectiveness; comparative safety; data mining; design; evidence base; experience; falls; follow-up; frailty; functional status; human old age (65+); improved; macrovascular disease; medical schools; mortality risk; multiple chronic conditions; novel; novel strategies; novel therapeutics; older patient; professor; programs; prospective; randomized placebo controlled trial; randomized trial; real time monitoring; response; routine care; statistics; treatment effect

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.

本申请为指导临床科学家研究职业发展奖（K 08）提交 Elisabetta Patorno，MD，DrPH对PA-16-191的回应。Patorno博士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，以及 哈佛医学院的医学助理教授。随着美国人口的快速增长，≥ 65 年，谁使用的药物比例最大，更好地了解药物的作用， 在日常护理中使用的老年人是必要的。这种需求对于通常 进入市场的证据的基础上，从相对较小，短，往往安慰剂对照随机 随机对照试验（RCT），其中老年患者往往代表性不足或被排除在外。因此，临床医生经常 他们很难为老年患者选择最好的治疗方法，特别是那些虚弱和多发性硬化的患者。 博士Patorno致力于作为一名独立的临床研究者的职业生涯，专注于推进 研究严格监测药物在老年人中的作用，如在常规护理中治疗。 为了实现这一目标，Patorno博士提出了一个为期4年的职业发展和指导研究计划 重点是开发一个有效的系统，以及时和高质量的证据， 专门针对老年患者的特殊护理方面的药物 例如虚弱和多Morphia。这种研究背景结合了对信息的迫切需要， 在过去十年中，FDA批准了10多种新的抗糖尿病药物， 在现实世界的老年人中开发前瞻性药物监测的新方法。在高度 药物流行病学部门的生产和支持性研究环境，Patorno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 大学，具有深厚的专业知识和国家/国际声誉，在具体的实质性领域， 她提议的培训：临床老年病学和糖尿病学，前瞻性监测和数据挖掘方法， 和老年人健康服务研究。她指导研究的首要目标是 创建并实施一种新的方法，用于近实时监测比较安全性， 新的糖尿病药物在常规治疗的老年患者中的有效性。这种新的监测 一种方法将使用医疗保险索赔数据，滞后时间相对较短，与电子医疗 医疗保险当前受益人调查（Medicare Current Beneficiary Survey）拟议的工作将提供及时和可操作的 治疗老年人的临床医生的知识，定义新的抗糖尿病药物的净增量值， 老年体弱多病患者。从这项工作中获得的知识将影响数百万人 美国的老年人，并将为申请人提供坚实的背景，成为一个独立的 研究人员，并最终领导者，在药物使用和结果的研究，在老龄化人口。

项目成果

Data Mining for Adverse Drug Events With a Propensity Score-matched Tree-based Scan Statistic.

• DOI: 10.1097/ede.0000000000000907
• 发表时间: 2018-11
• 期刊: Epidemiology (Cambridge, Mass.)
• 作者: Wang SV;Maro JC;Baro E;Izem R;Dashevsky I;Rogers JR;Nguyen M;Gagne JJ;Patorno E;Huybrechts KF;Major JM;Zhou E;Reidy M;Cosgrove A;Schneeweiss S;Kulldorff M
• 通讯作者: Kulldorff M

Safety and Effectiveness of Direct Oral Anticoagulants Versus Vitamin K Antagonists: Pilot Implementation of a Near-Real-Time Monitoring Program in Italy.

• DOI: 10.1161/jaha.117.008034
• 发表时间: 2018-03-10
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Mayer F;Kirchmayer U;Coletta P;Agabiti N;Belleudi V;Cappai G;Di Martino M;Schneeweiss S;Davoli M;Patorno E
• 通讯作者: Patorno E

Bias Implications of Outcome Misclassification in Observational Studies Evaluating Association Between Treatments and All-Cause or Cardiovascular Mortality Using Administrative Claims.

• DOI: 10.1161/jaha.120.016906
• 发表时间: 2020-09
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Desai RJ;Levin R;Lin KJ;Patorno E
• 通讯作者: Patorno E

A novel data mining application to detect safety signals for newly approved medications in routine care of patients with diabetes.

• DOI: 10.1002/edm2.237
• 发表时间: 2021-07
• 期刊: Endocrinology, diabetes & metabolism
• 作者: Fralick M;Kulldorff M;Redelmeier D;Wang SV;Vine S;Schneeweiss S;Patorno E
• 通讯作者: Patorno E

Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA1c Levels.

• DOI: 10.1001/jamainternmed.2022.6664
• 发表时间: 2023-03-01
• 期刊: JAMA INTERNAL MEDICINE
• 影响因子: 39
• 作者: D'Andrea, Elvira;Wexler, Deborah J.;Kim, Seoyoung C.;Paik, Julie M.;Alt, Ethan;Patorno, Elisabetta
• 通讯作者: Patorno, Elisabetta