Development and Validation of a Frailty Index Using Claims Data for Pharmacoepidemiologic Studies in Older Adults

使用老年人药物流行病学研究的索赔数据开发和验证虚弱指数

• 批准号: 8966383
• 负责人: Dae Hyun Kim
• 金额: $ 21.42万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8966383
• 关键词: Address; Adult; Adverse event; Affect; Age; Aging; Algorithms; Anticoagulants; Anticoagulation; Area; Atrial Fibrillation; Award; Caring; Cessation of life; Characteristics; Clinical; Clinical Trials; Cohort Studies; Communities; Complement; Data; Data Set; Databases; Decision Making; Development; Dimensions; Drug Evaluation; Drug usage; Drug user; Effectiveness; Elderly; Environment; Epidemiologic Methods; Epidemiologist; Epidemiology; Equilibrium; Evaluation; Event; Frail Elderly; Frail Older Adults; Geriatrics; Goals; Health; Health Status; Hemorrhage; Heterogeneity; Hospital Departments; Hospitals; Individual; Intervention; Knowledge; Leadership; Measures; Medical; Medicare; Medicine; Mentors; Methods; Mission; Modeling; Modification; National Institute on Aging; Observational Study; Oral; Outcome; Patient Selection; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Phenotype; Physiological; Population; Positioning Attribute; Public Health; Publishing; Relative (related person); Research; Research Personnel; Retirement; Safety; Sampling; Scientist; Selection for Treatments; Solid; Source; Stressful Event; Stroke; Surveys; Testing; Therapeutic; Treatment Effectiveness; Treatment outcome; Tweens; Uncertainty; United States National Institutes of Health; Validation; Variant; Warfarin; Woman; Work; adverse outcome; age group; aged; base; beneficiary; career; career development; clinical care; clinical decision-making; comparative effectiveness; data sharing; disability; experience; falls; frailty; functional outcomes; health care service utilization; improved; indexing; individualized medicine; innovation; insight; instructor; medical schools; neglect; novel strategies; older patient; population based; programs; public health relevance; research and development; response; safety study; tool; treatment effect

 DESCRIPTION (provided by applicant): This application is submitted by Dae Hyun Kim, MD, MPH, ScD in response to RFA-AG-15-016, the K08 Paul B. Beeson Clinical Scientist Development Award in Aging. Dr. Kim is a board-certified geriatrician and epidemiologist at Brigham and Women's Hospital and Instructor in Medicine at Harvard Medical School. Dr. Kim has a solid background in clinical geriatric medicine, epidemiologic methods, and aging epidemiology. His prior research focused on epidemiologic evaluations of functional outcomes using population-based and hospital- based cohort studies, from which he gained insight on how the assessment of frailty could improve the care of older adults. Because frailty is a state of decreased physiologic reserve and increased vulnerability to adverse health outcomes after a stressful event, frail older patients are more likely than non-frail ones to experience adverse outcomes after certain treatments. Therefore, treatment selection should be personalized based on individuals' frailty level so as to maximize benefits and minimize harms. Pharmacoepidemiology in geriatric population remains an underdeveloped field that has great potential to provide important evidence on drug effectiveness and safety to guide treatment choices in frail older adults. Dr. Kim proposes an independent re- search career in geriatric pharmacoepidemiology with a long-term goal of establishing a method for incorporating the key but neglected dimension of frailty in assessing the effectiveness and safety of treatments in older adults. To achieve this, Dr. Kim proposes a 3-year program of career development and mentored research. Within the highly productive and supportive research environment of the Pharmacoepidemiology Division of the Brigham and Women's Hospital Department of Medicine and the larger Harvard community, he will work closely with Drs. Jerry Avorn, Sebastian Schneeweiss, Robert Glynn, and Lewis Lipsitz who will serve as his men- tors in aging and pharmacoepidemiology research. He will acquire expertise in advanced methods and build his leadership potential to become a national leader in geriatric pharmacoepidemiology. The objective of his mentored research is to develop and validate a frailty index using large datasets of health care utilization (or claims data) for pharmacoepidemiologic studies in older adults. Such observational studies are often the main sources of evidence to guide treatments in frail older adults who are poorly represented in clinical trials. How- ever, the lack of detailed clinica information on frailty in such datasets limits the ability to balance frailty be- tween treatment groups (confounding by frailty). In addition, the clinically important question of whether treatmen outcomes differ between frail and non-frail adults remains unanswered (effect modification by frailty). The significance of developing a generalizable algorithm to assess frailty in claims datasets is that we will be able to achieve balance in frailty and assess potential variation in treatment effects by frailty level in claims- based comparative effectiveness and safety research. This proposed research is innovative because it goes beyond the existing methods of confounding adjustment by directly quantifying frailty in claims datasets through application of a widely accepted frailty model in aging research (the cumulative deficit frailty index pro- posed by Rockwood et al). The derived frailty index will make it possible to measure how treatment effective- ness and safety differ between frail and non-frail adults, which cannot be examined using the existing methods. To achieve the objective, Dr. Kim will accomplish the following 2 specific aims. Aim 1 is to derive a cumulative deficit frailty index using claims in the Medicare Current Beneficiary Survey dataset, and then test its validity in an independent Health and Retirement Study-Medicare dataset. The working hypothesis is that individuals with higher claims-based frailty index scores are more likely to have clinical characteristics of frailty, fall, disability, and death than those with lower scores. Aim 2 is to validate the usefulness of this claims-based frailty index in comparative effectiveness and safety evaluation of new oral anticoagulants versus warfarin in Medicare beneficiaries with atrial fibrillation. In this real-word example, we will test the improved adjustment for confounding by frailty by reproducing the results from clinical trials by using the claims-based frailty index. To assess potential effect modification by frailty, I will test the working hypothesis that the overall benefits of new oral anticoagulants versus warfarin in reducing stroke, death, and major bleeding events are greater in frail individuals than in non-frail individuals. Ultimately, successful accomplishment of these aims is expected to have a significant impact on future research and clinical care. The proposed research will yield a novel approach to measure frailty in health care utilization datasets that complement the existing methods in defining medical product effectiveness and safety in older adults. In addition, the substantive knowledge gained from this research will guide future research on database research as well as individualized treatment choice about anticoagulation therapy by frailty status in older adults with atrial fibrillation. Finally, the proposed career development program and mentored research will position Dr. Kim to successfully compete for an NIH R01 award and become a national leader in geriatric pharmacoepidemiology research.

 描述（由申请人提供）：本申请由Dae Hyun Kim，MD，MPH，ScD提交，以响应RFA-AG-15-016，K 08 Paul B。Beeson老龄化临床科学家发展奖。金博士是布里格姆妇女医院的老年病学家和流行病学家，也是哈佛医学院的医学讲师。金博士在临床老年医学、流行病学方法和老龄流行病学方面有着坚实的背景。他之前的研究主要集中在使用基于人群和基于医院的队列研究对功能结局进行流行病学评估，从中他获得了对虚弱评估如何改善老年人护理的见解。因为脆弱是一种 由于生理储备减少和在压力事件后对不良健康结果的脆弱性增加，虚弱的老年患者比非虚弱的患者更有可能在某些治疗后经历不良结果。因此，治疗选择应根据个人的脆弱程度进行个性化，以最大限度地提高效益，减少危害。老年人群的药物流行病学仍然是一个欠发达的领域，具有很大的潜力，提供重要的证据，药物的有效性和安全性，以指导治疗选择体弱老年人。Kim博士提出在老年药物流行病学领域开展独立研究，其长期目标是建立一种方法，将关键但被忽视的虚弱维度纳入老年人治疗的有效性和安全性评估。为了实现这一目标，金博士提出了一个为期3年的职业发展和指导研究计划。在布里格姆妇女医院医学部药物流行病学部门和更大的哈佛社区的高效和支持性研究环境中，他将与Jerry Avorn、塞巴斯蒂安Schneeweiss、Robert Glynn和刘易斯Lipsitz博士密切合作，他们将担任他在衰老和药物流行病学研究方面的导师。他将获得先进方法的专业知识，并建立自己的领导潜力，成为老年药物流行病学的国家领导者。他的指导研究的目标是开发和验证一个脆弱指数使用大型数据集的医疗保健利用（或索赔数据）的药物流行病学研究在老年人。这些观察性研究通常是指导临床试验中代表性较差的虚弱老年人治疗的主要证据来源。然而，在这些数据集中缺乏关于虚弱的详细临床信息限制了在治疗组之间平衡虚弱的能力（虚弱混杂）。此外，虚弱和非虚弱成人之间的治疗结果是否不同的临床重要问题仍然没有答案（虚弱的效果修改）。开发一种可推广的算法来评估声明数据集中的脆弱性的意义在于，我们将能够在基于声明的比较有效性和安全性研究中实现脆弱性的平衡，并评估治疗效果的潜在差异。这项研究是创新的，因为它超越了现有的混杂调整方法，通过应用老龄化研究中广泛接受的脆弱模型（由 罗克伍德等人）。推导出的虚弱指数将能够衡量虚弱和非虚弱成年人之间治疗有效性和安全性的差异，这是使用现有方法无法检查的。为了实现这一目标，金博士将实现以下两个具体目标。目标1是使用Medicare Current Beneficiary Survey数据集中的索赔来推导累积赤字脆弱指数，然后在独立的Health and Retirement Study-Medicare数据集中测试其有效性。工作假设是，具有较高基于索赔的虚弱指数得分的个体比具有较低得分的个体更可能具有虚弱、跌倒、残疾和死亡的临床特征。目的2是验证这种基于索赔的虚弱指数在比较新的口服抗凝剂与华法林在患有房颤的医疗保险受益人中的有效性和安全性评价中的有用性。在这个真实的例子中，我们将通过使用基于索赔的虚弱指数重现临床试验的结果来测试虚弱混杂的改进调整。为了评估虚弱的潜在效应改变，我将检验工作假设，即新的口服抗凝剂与华法林相比，在减少中风、死亡和大出血事件方面，虚弱个体的总体获益大于非虚弱个体。最终，这些目标的成功实现预计将对未来的研究和临床护理产生重大影响。拟议的研究将产生一种新的方法来衡量医疗保健利用数据集的脆弱性，补充现有的方法来定义医疗产品在老年人中的有效性和安全性。此外，从本研究中获得的实质性知识将指导未来的数据库研究以及老年房颤患者根据虚弱状态进行抗凝治疗的个体化治疗选择。最后，拟议的职业发展计划和指导研究将使金博士成功竞争NIH R 01奖，并成为老年药物流行病学研究的全国领导者。