Safety and Effectiveness Evaluations for Kidney Disease in Complex Patients

复杂患者肾脏疾病的安全性和有效性评估

• 批准号: 8015897
• 负责人: DONALD R MILLER
• 金额: $ 50万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015897
• 关键词: Safety; Effectiveness; Evaluations; Kidney; Disease

DESCRIPTION (provided by applicant): This application addresses broad needs for comparative effectiveness research and proposes to conduct and analytic epidemiologic studies of retrospective cohort design, to assess the benefits and harms of preventive or therapeutic interventions in "real world" settings for patients who have multiple chronic co morbid conditions. It proposes research on chronic kidney disease (CKD) in diabetes patients and its progression to end stage renal disease (ESRD), conditions that are devastating and increasingly prevalent, with high mortality and high direct costs of care. Although a number of treatments are widely recommended for slowing progression of CKD and reducing risks of associated cardiovascular disease (CVD), ESRD, and mortality, there is little experimental evidence to support these recommendations and there have been few trials comparing drugs within classes in terms of effectiveness and safety. Such trials are unlikely to be done in the near future and much can be learned from careful observational studies of existing patient data to identify the most safe and effective treatments. We propose to conduct such studies in the diabetes patient population served by the Veterans Health Administration (VA), the largest sample of older adults in an integrated health care system in the U.S. with comprehensive electronic medical records. These patients have high prevalence of CKD and other morbidities, and represent those who are often excluded from clinical trials. We have shown in our previous work that large, rigorous, longitudinal studies can be done in the VA and we have developed and evaluated methodologies for such research. We now propose to study complex diabetes patients with CKD and other co-morbidities in order to evaluate comparative effectiveness and safety in slowing the progression of kidney disease (decline in estimated glomerular filtration rate (eGFR), transition in CKD stage, transition to ESRD), reducing risks of other outcomes (CVD events, mortality), and having low associated risks of medication-related adverse renal outcomes (acute kidney injury, hyperkalemia) and other adverse events (hypoglycemia, angioedema, falls). Class-to class and drug-to-drug comparisons will be made within the following classes or groups of medications recommended for treating CKD: angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and HMGcoA reductase inhibitors (statins). Samples and exposure groups will be selected carefully to replicate common clinical decisions in treatment and up to 11 years of national data will be used with application of rigorous epidemiologic methods to reduce potential bias and provide valid and meaningful results. This research represents a real opportunity to better understand benefits and risks associated with treatments for CKD in complex diabetes patients and application of its findings should result in safer and more effective prescribing practices. PUBLIC HEALTH RELEVANCE: Chronic kidney disease is a common, debilitating condition in older people with diabetes that is associated with premature mortality and high costs of care. A number of medication classes have been recommended for preventing or slowing progression of the disease but there is little evidence to support these recommendations in complex diabetic patients and more information is needed on which drugs are most safe and effective. We propose to study the comparative effective and safety of these drugs in complex diabetes patients with chronic kidney disease who receive care at the Veterans Health Administration. Patients will be studied over an eleven year period in order to determine which drugs are the most beneficial and safe. This information should guide future prescribing practices and reduce the burden of this disease in our aging population.

描述(由申请人提供)：这项申请解决了比较有效性研究的广泛需求，并建议进行回顾队列设计的分析性流行病学研究，以评估预防或治疗干预措施对患有多种慢性并存疾病的患者的益处和危害。它建议对糖尿病患者的慢性肾脏疾病(CKD)及其进展为终末期肾病(ESRD)进行研究，这些疾病具有破坏性且日益流行，具有高死亡率和高直接护理成本。虽然许多治疗方法被广泛推荐用于减缓CKD的进展并降低相关心血管疾病(CVD)、终末期肾病(ESRD)和死亡率的风险，但几乎没有实验证据支持这些建议，也很少有试验比较类内药物的有效性和安全性。这样的试验不太可能在不久的将来进行，从对现有患者数据的仔细观察研究中可以学到很多东西，以确定最安全和有效的治疗方法。我们建议在退伍军人健康管理局(VA)服务的糖尿病患者群体中进行这样的研究，退伍军人健康管理局是美国综合医疗保健系统中最大的老年人样本，拥有全面的电子医疗记录。这些患者有很高的CKD和其他疾病的患病率，并代表那些经常被排除在临床试验之外的人。我们在以前的工作中已经表明，可以在退伍军人管理局进行大规模、严格的纵向研究，我们已经为此类研究开发和评估了方法。我们现在建议对合并CKD和其他并发症的复杂糖尿病患者进行研究，以评估在减缓肾脏疾病进展(估计的肾小球滤过率(EGFR)下降、CKD阶段的过渡、过渡到ESRD)、降低其他结果的风险(心血管事件、死亡率)、以及与药物相关的不良肾脏结果(急性肾损伤、高钾血症)和其他不良事件(低血糖、血管水肿、跌倒)的低相关风险方面的比较有效性和安全性。将在以下推荐用于治疗CKD的药物类别或组内进行类别对类别和药物对药物的比较：血管紧张素转换酶抑制剂、血管紧张素II受体阻滞剂和HMGcoA还原酶抑制剂(他汀类)。将仔细选择样本和暴露组，以复制治疗中的常见临床决定，并将使用长达11年的国家数据，并应用严格的流行病学方法，以减少潜在的偏见，并提供有效和有意义的结果。这项研究代表着一个真正的机会，可以更好地了解与复杂糖尿病患者CKD治疗相关的益处和风险，其结果的应用将导致更安全和更有效的处方实践。 公共卫生相关性：慢性肾脏疾病是老年糖尿病患者中一种常见的、使人虚弱的疾病，与过早死亡和高昂的护理成本有关。一些药物类别已被推荐用于预防或减缓疾病的进展，但在复杂的糖尿病患者中几乎没有证据支持这些建议，还需要更多关于哪些药物最安全和有效的信息。我们建议研究这些药物在退伍军人健康管理局接受护理的复杂糖尿病合并慢性肾脏疾病患者中的比较有效性和安全性。将对患者进行为期11年的研究，以确定哪些药物最有益、最安全。这些信息应该指导未来的处方实践，并减少这种疾病在我们老龄化人口中的负担。