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

评估多种疾病在调节老年人药物作用中的作用

• 批准号: 10586349
• 负责人: Chintan Dave
• 金额: $ 70.03万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586349
• 关键词: Address; Adult; Adverse reactions; Affect; Aging; Anticoagulants; Antidiabetic Drugs; Antiplatelet Drugs; Area; Atherosclerosis; Atrial Fibrillation; Benefits and Risks; Cardiovascular Diseases; Cardiovascular system; Caregivers; Cessation of life; Clinical; Clinical Data; Clinical Trials; Data; Databases; Dementia; Disease; Drug Prescriptions; Drug Utilization; Effectiveness; Elderly; Event; Evidence based treatment; Exclusion; Fee-for-Service Plans; Geriatrics; Glucose; Healthcare; Hemorrhage; Heterogeneity; High Prevalence; Home; Impaired cognition; Individual; Link; Longevity; Measures; Medical; Medicare; Methods; Morbidity - disease rate; New Agents; Non-Insulin-Dependent Diabetes Mellitus; Nursing Homes; Observational Study; Oral; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Physical Function; Play; Polypharmacy; Population; Prevalence; Research; Role; Safety; Sodium; Source; Surveys; Time; Warfarin; beneficiary; burden of illness; cardiometabolism; clinically relevant; clopidogrel; cognitive function; cost; electronic health database; evidence base; functional independence; functional loss; health data; indexing; inhibitor; innovation; middle age; mortality; multiple chronic conditions; novel; social deprivation; social health determinants; social vulnerability; symporter; treatment effect; uptake

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.

多重发病率被定义为两种或两种以上医疗状况同时发生，影响了三分之二的老年人 65 岁以上的个人——相当于 3600 万美国成年人，是医疗保健支出的主要驱动力， 然而，老年和多病患者通常被排除在临床之外。 试验导致缺乏关于该人群中药物的风险和益处的数据，或者 了解多发病如何改变治疗效果 为了解决这一未满足的需求，该提案将 评估多发病在调节药物效果中的作用，并确定最有效的最佳方法 我们的中心假设是（a）通过减弱药物相关性来量化其对药物结果的影响。 由于药物带来的益处和放大与药物相关的危害，多重疾病应成为治疗时的一个关键考虑因素 决策，以及 (b) 纳入疾病累积负担的方法，尤其是多重疾病负担 发病率加权指数 [MWI] – 可以更好地表征药物效果的这些变化（初步 该提案将使用来自超过 2300 万患者的 Medicare 按服务收费数据，并复制研究结果 我们将重点关注两个大型外部数据库：老年人的比例最高。 自 2010 年以来，已有 20 多种新的心脏代谢疗法获得批准， 强调研究这些药物的巨大需求，我们将确定患有以下疾病的患者：(a) 2 型糖尿病。 起始钠葡萄糖协同转运蛋白 2 抑制剂与现有抗糖尿病疗法的对比；(b) 心房颤动； 开始直接口服抗凝剂与华法林；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（例如替格瑞洛）与氯吡格雷的比较目标 1 将评估临床效果（例如认知能力）。 损伤）和非临床（例如社会剥夺）因素与多发病相互作用，影响药物治疗 目标 2 将阐明现实世界中心脏代谢疗法的作用。 通过估计来调整与现有心脏代谢药物相比的新药物的风险和益处 调整后的疾病特定益处（即减少 CVD 事件）、危害（例如大出血）和 按多种发病程度划分的普遍结果衡量标准（例如，在家工作、功能独立性丧失）。 还将验证多重发病率测量（例如 MWI、Elixhauser 指数）和框架（例如疾病二元组） 该提案的影响是重大的，因为它将建立严格且容易的方法。 研究多种疾病对老年人药物结果影响的可扩展框架。 系统评估和验证多重发病指数和药物治疗方法的首次努力 结果，开始了一个新的、令人兴奋的研究领域，该研究有可能扩展到其他人群（例如， 鉴于临床试验数据的缺乏，研究结果将作为参考。 患者、护理人员和忠诚者的主要信息来源，以基于证据进行个性化治疗 决定。