Evaluating the role of multimorbidity in modulation medication effects in older adults

多发病，定义为同时发生两种或多种医疗条件，影响三分之二的老年人， 65岁以上的人-相当于3600万美国成年人，是医疗保健支出的主要驱动力， 多药治疗和死亡率。然而，常规排除老年人和更多的多病患者从临床 临床试验导致关于该人群中药物的风险和益处的数据缺乏，或者 了解多药疗法如何改变治疗效果。为了满足这一未满足的需求，本提案将 评估多药治疗在调节药物作用中的作用，并确定最佳方法， 量化其对药物治疗结果的影响。我们的中心假设是，（a）通过减弱与药物有关的 药物的益处和放大与药物相关的危害，多药疗法应该是治疗时的一个关键考虑因素 （B）将疾病的累积负担-特别是多重-纳入的方法， 发病率加权指数[MWI] -可以更好地描述这些药物作用的变化（初步 分析）。该提案将使用来自超过2300万患者的医疗保险按服务收费数据，并在 两大外部数据库。我们将重点关注心脏代谢疗法，因为：老年人的心脏代谢率最高， 自2010年以来，已经批准了20多种新的心脏代谢疗法， 强调了研究这些药物的巨大需求。2型糖尿病的治疗方法 开始钠葡萄糖协同转运蛋白2抑制剂与已建立的抗糖尿病疗法;（B）心房纤颤 开始直接口服抗凝剂vs华法林;和（c）开始动脉粥样硬化性心血管疾病[CVD] 较新的抗血小板药物（如替格瑞洛）与氯吡格雷。目标1将评估临床（例如认知） 损伤）和非临床（如社会剥夺）因素与多发病相互作用，影响药物治疗 在真实的世界中开心脏代谢疗法的处方。目的2将阐明多聚体在 通过估计新药物与已确立的心脏代谢药物相比的风险和获益， 疾病特定获益（即CVD事件减少）、危害（例如大出血）和 按多功能水平的普遍结局指标（如在家时间、功能独立性丧失）。我们 还将验证多变量指标（如MWI、Elixhauser指数）和框架（如疾病二元组） 与药物治疗结果的对比这一建议的影响是重大的，因为它将建立一个严格的， 可扩展的框架，以研究多吗啡对老年人药物结果的影响。它也将代表 第一次系统地评估和验证针对药物治疗的多指标和方法 结果，开始了一个新的和令人兴奋的研究，有可能扩大到其他人群（例如， 中年人）和临床领域。鉴于临床试验数据的缺乏，研究结果将作为 患者、护理人员和临床医生进行个性化循证治疗的主要信息来源 决策

Multimorbidity, defined as the co-occurrence of two or more medical conditions, impacts two-thirds of older individuals over 65 – corresponding to 36 million U.S. adults, and is a major driver of healthcare spending, polypharmacy, and mortality. However, the routine exclusion of older and more multimorbid patients from clinical trials has resulted in the paucity of data regarding the risks and benefits of medications in this population, or an understanding of how multimorbidity alters treatment effects. To address this unmet need, this proposal will evaluate the role of multimorbidity in modulating medication effects and identify the optimal approach that best quantifies its impact on medication outcomes. Our central hypothesis is that (a) by attenuating drug-related benefits and amplifying drug-related harms, multimorbidity should be a key consideration when making treatment decisions, and that (b) approaches that incorporate the cumulative burden of illness – especially the multi- morbidity weighted index [MWI] – can better characterize these alterations in medication effects (preliminary analysis). The proposal will use Medicare fee-for-service data from >23 million patients and replicate findings in two large external databases. We will focus on cardiometabolic therapies as: older adults have the highest burden of these conditions, and since 2010, more than 20 new cardiometabolic therapies have been approved, highlighting the immense need to study these medications. We will identify patients with: (a) type 2 diabetes initiating sodium glucose co-transporter 2 inhibitors vs established antidiabetic therapies; (b) atrial fibrillation initiating direct oral anticoagulants vs warfarin; and (c) atherosclerotic cardiovascular disease [CVD] initiating newer antiplatelet drugs (e.g. ticagrelor) vs clopidogrel. Aim 1 will evaluate how clinical (e.g. cognitive impairment) and non-clinical (e.g. social deprivation) factors interact with multimorbidity to influence medication prescribing of cardiometabolic therapies in the real world. Aim 2 will elucidate the role of multimorbidity in modulating the risks and benefits for newer compared to established cardiometabolic medications by estimating the adjusted rates of disease specific benefits (i.e. reduction in CVD events), harms (e.g. major bleeding) and universal outcome measures (e.g. home-time, loss of functional independence) by levels of multimorbidity. We will also validate multimorbidity measures (e.g. MWI, Elixhauser index) and frameworks (e.g. disease dyads) against medication outcomes. The impact of this proposal is significant as it will establish a rigorous and readily scalable framework to study the effects of multimorbidity on drug outcomes in older adults. It will also represent the first effort to systematically evaluate and validate multimorbidity indices and approaches against medication outcomes, beginning a new and exciting line of research that has potential to expand to other populations (e.g. middle-aged adults) and clinical areas. Given the paucity of data from clinical trials, study findings will serve as the primary source of information for patients, caregivers, and clinicians to make individualized evidence-based decisions.