GFR Decline as an End Point for Clinical Trials in CKD: A Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration
GFR Decline as an End Point for Clinical Trials in CKD: A Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration
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DOI：
10.1053/j.ajkd.2014.07.030
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发表时间：
2014-12-01
影响因子：
13.2
通讯作者：
Coresh, Josef
中科院分区：
文献类型：
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作者：
Levey, Andrew S.;Inker, Lesley A.;Coresh, Josef
在肾脏疾病进展的临床试验中，美国食品和药物管理局目前接受将肾小球滤过率(GFR)减半(评估为血清肌酐水平加倍)作为发生肾衰竭的替代终点。在慢性肾脏疾病(CKD)中，血清肌酐水平翻倍通常是一种晚期事件；因此，考虑临床试验的替代终点以缩短持续时间、减少样本量并将其推广到CKD早期患者是非常有兴趣的。然而，肾小球滤过率较小的下降与随后发生的肾衰竭之间的关系还没有得到很好的描述。国家肾脏基金会和食品和药物管理局赞助了一次科学研讨会，以严格检查现有数据，以确定替代的基于GFR的终点是否与CKD的重要临床结果有足够强的关系，可用于临床试验。根据对队列和临床试验的一系列荟萃分析以及对试验设计和分析方法的模拟，研讨会得出结论，在某些情况下，估计的GFR下降30%在某些情况下可能是一个可接受的替代终点，但必须检查对GFR的治疗效果模式，特别是对估计的GFR的急性影响。在更大范围的基线GFR和治疗对GFR的影响模式中，估计40%的GFR下降可能比30%的下降更能被广泛接受。然而，在其他情况下，这些终点可能会导致统计能力的降低或关于干预措施的益处或危害的错误结论。我们鼓励在未来临床试验的设计中仔细考虑这些替代终点。(C)2014年，由国家肾脏基金会公司提供。
The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level generally is a late event in chronic kidney disease (CKD); thus, there is great interest in considering alternative end points for clinical trials to shorten their duration, reduce sample size, and extend their conduct to patients with earlier stages of CKD. However, the relationship between lesser declines in GFR and the subsequent development of kidney failure has not been well characterized. The National Kidney Foundation and Food and Drug Administration sponsored a scientific workshop to critically examine available data to determine whether alternative GFR-based end points have sufficiently strong relationships with important clinical outcomes of CKD to be used in clinical trials. Based on a series of meta-analyses of cohorts and clinical trials and simulations of trial designs and analytic methods, the workshop concluded that a confirmed decline in estimated GFR of 30% over 2 to 3 years may be an acceptable surrogate end point in some circumstances, but the pattern of treatment effects on GFR must be examined, specifically acute effects on estimated GFR. An estimated GFR decline of 40% may be more broadly acceptable than a 30% decline across a wider range of baseline GFRs and patterns of treatment effects on GFR. However, there are other circumstances in which these end points could lead to a reduction in statistical power or erroneous conclusions regarding benefits or harms of interventions. We encourage careful consideration of these alternative end points in the design of future clinical trials. (C) 2014 by the National Kidney Foundation, Inc.