Utility and Validity of Estimated GFR-Based Surrogate Time-to-Event End Points in CKD: A Simulation Study
Utility and Validity of Estimated GFR-Based Surrogate Time-to-Event End Points in CKD: A Simulation Study
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DOI：
10.1053/j.ajkd.2014.08.019
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发表时间：
2014-12-01
影响因子：
13.2
通讯作者：
Levey, Andrew S.
中科院分区：
文献类型：
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作者：
Greene, Tom;Teng, Chia-Chen;Levey, Andrew S.
背景资料：慢性肾脏疾病进展的临床试验的替代终点很有意义，因为目前确定的终点终末期肾病（ESRD）和血清肌酐水平加倍是晚期事件，需要长期随访的大型临床试验。血清肌酐水平加倍相当于估计肾小球滤过率（eGFR）下降57%。我们使用基于eGFR下降较小的替代终点评估了临床试验的1型错误和所需样本量。研究设计：模拟研究。设置和参与者：模拟评估了13项慢性肾脏病临床试验中19种治疗比较的3，060种情况。指数检验：替代终点定义为基于ESRD和eGFR下降30%或40%的复合终点。参考试验：1型错误的临床结局（ESRD）。结果：使用40%与57%eGFR下降终点一致导致样本量减少> 20%，同时在存在小的急性效应的情况下保持1型错误风险< 10%。
Background: There is interest in surrogate end points for clinical trials of chronic kidney disease progression because currently established end points-end-stage renal disease (ESRD) and doubling of serum creatinine level-are late events, requiring large clinical trials with long follow-up. Doubling of serum creatinine level is equivalent to a 57% decline in estimated glomerular filtration rate (eGFR). We evaluated type 1 error and required sample size for clinical trials using surrogate end points based on lesser eGFR declines.Study Design: Simulation study.Setting & Participants: Simulations evaluating 3,060 scenarios representative of 19 treatment comparisons in 13 chronic kidney disease clinical trials.Index Tests: Surrogate end points defined as composite end points based on ESRD and either 30% or 40% eGFR declines.Reference Test: Clinical outcome (ESRD) for type 1 error. Established end point (composite of ESRD and 57% eGFR decline) for required sample size.Results: Use of the 40% versus 57% eGFR decline end point consistently led to a reduction in sample size > 20% while maintaining risk for type 1 error < 10% in the presence of a small acute effect (