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

 描述(申请人提供)：本申请由医学博士、公共卫生硕士、医学博士Dae Hyun Kim提交，以回应K08 Paul B.Beeson临床科学家老龄发展奖RFA-AG-15-016。金博士是布里格姆妇女医院董事会认证的老年病学家和流行病学家，也是哈佛医学院的医学讲师。金博士在老年临床医学、流行病学方法和老龄流行病学方面有扎实的背景。他之前的研究重点是使用基于人群和基于医院的队列研究对功能结果进行流行病学评估，从这些研究中，他获得了关于虚弱评估如何改善老年人护理的见解。因为脆弱是一种状态 在应激事件后，由于生理储备减少和对不利健康结果的易感性增加，虚弱的老年患者比非虚弱的老年患者在某些治疗后更有可能经历不良结果。因此，治疗选择应根据个体的脆弱程度进行个性化选择，以实现利益最大化和伤害最小化。老年人群的药物流行病学仍然是一个不发达的领域，有很大的潜力提供关于药物有效性和安全性的重要证据，以指导虚弱老年人的治疗选择。金博士建议在老年药物流行病学领域开展一项独立的研究，其长期目标是建立一种方法，在评估老年人治疗的有效性和安全性时，将脆弱这一关键但被忽视的因素纳入其中。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性研究计划。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高效和支持的研究环境中，他将与曾傑瑞·埃沃恩博士、塞巴斯蒂安·施尼韦斯博士、罗伯特·格林博士和刘易斯·利普西茨博士密切合作，他们将担任他在老龄化和药物流行病学研究方面的助手。他将获得先进方法方面的专业知识，并建立他的领导潜力，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利用医疗保健利用的大型数据集(或索赔数据)开发和验证脆弱指数，用于老年人的药物流行病学研究。这种观察性研究往往是指导虚弱老年人治疗的主要证据来源，而这些老年人在临床试验中的代表性很低。然而，在这样的数据集中缺乏关于脆弱的详细的临床信息限制了在治疗组之间平衡脆弱的能力(因脆弱而混淆)。此外，虚弱和非虚弱成人之间的治疗结果是否不同这一临床上重要的问题仍未得到回答(虚弱对疗效的影响)。开发一种可推广的算法来评估索赔数据集中的脆弱性的意义在于，我们将能够在脆弱性中实现平衡，并在基于索赔的比较有效性和安全性研究中根据脆弱性水平来评估治疗效果的潜在变化。这项拟议的研究具有创新性，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性模型(提出的累积赤字脆弱性指数)，直接量化索赔数据集中的脆弱性 Rockwood等人)。导出的脆弱指数将使衡量虚弱和非虚弱成年人之间的治疗有效性和安全性的差异成为可能，这一点无法使用现有方法进行检查。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是使用联邦医疗保险当前受益人调查数据集中的索赔推导出累积赤字脆弱指数，然后在独立的健康和退休研究-联邦医疗保险数据集中测试其有效性。工作假设是，与得分较低的人相比，基于索赔的脆弱指数得分较高的人更有可能具有虚弱、跌倒、残疾和死亡的临床特征。目的2是验证这一基于声明的脆弱指数在比较新型口服抗凝剂与华法林对患有房颤的医疗保险受益者的有效性和安全性方面的有效性。在这个真实的例子中，我们将通过使用基于索赔的脆弱性指数重现临床试验的结果来测试针对脆弱性混杂的改进调整。为了评估虚弱对潜在效果的影响，我将测试工作假设，即在减少中风、死亡和主要出血事件方面，新的口服抗凝剂与华法林相比，在虚弱个体中的总体益处大于非虚弱个体。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。这项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，这是对现有方法的补充，用于定义老年人的医疗产品有效性和安全性。此外，本研究所获得的实质性知识将指导未来针对老年房颤患者虚弱状态进行抗凝治疗的数据库研究和个体化治疗选择。最后，拟议的职业发展计划和指导性研究将使Kim博士成功角逐NIH R01奖，并成为老年药物流行病学研究的全国领导者。

 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.