Safety and Effectiveness Evaluations for Kidney Disease in Complex Patients

描述（由申请人提供）：本申请针对比较有效性研究的广泛需求，并建议进行回顾性队列设计的流行病学研究和分析，以评估在“现实世界”环境中对患有多种慢性合并症的患者进行预防或治疗干预的利与弊。它建议研究糖尿病患者的慢性肾脏疾病（CKD）及其向终末期肾脏疾病（ESRD）的进展，这些疾病具有破坏性且日益普遍，具有高死亡率和高直接护理成本。尽管许多治疗方法被广泛推荐用于减缓CKD的进展和降低相关心血管疾病（CVD）、ESRD和死亡率的风险，但很少有实验证据支持这些建议，并且很少有在有效性和安全性方面比较同类药物的试验。这种试验不太可能在不久的将来进行，可以从对现有患者数据的仔细观察研究中学到很多东西，以确定最安全有效的治疗方法。我们建议在退伍军人健康管理局（VA）服务的糖尿病患者人群中进行此类研究，VA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。这些患者有较高的CKD患病率和其他发病率，并且经常被排除在临床试验之外。我们在之前的工作中表明，可以在退伍军人事务部进行大规模、严格的纵向研究，我们已经开发并评估了此类研究的方法。我们现在建议研究CKD和其他合并症的复杂糖尿病患者，以评估减缓肾脏疾病进展（估计肾小球滤过率（eGFR）下降，CKD阶段过渡，向ESRD过渡），降低其他结局（CVD事件，死亡率）的风险，以及药物相关不良肾脏结局（急性肾损伤，急性肾损伤）的低相关风险的相对有效性和安全性。高钾血症)和其他不良事件（低血糖、血管性水肿、跌倒）。将对推荐用于治疗CKD的以下类别或组的药物进行分类和药物间的比较：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（他汀类药物）。将仔细选择样本和暴露组，以重复治疗中的常见临床决策，并将采用严格的流行病学方法使用长达11年的国家数据，以减少潜在的偏倚，并提供有效和有意义的结果。这项研究为更好地了解复杂糖尿病患者CKD治疗的益处和风险提供了一个真正的机会，其研究结果的应用应该导致更安全、更有效的处方实践。

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.