Evaluation of Trial Outcomes in Acute Kidney Injury by Creatinine Modeling
Evaluation of Trial Outcomes in Acute Kidney Injury by Creatinine Modeling
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DOI：
10.2215/cjn.00820209
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发表时间：
2009-11-01
影响因子：
9.8
通讯作者：
Endre, Zoltan H.
中科院分区：
文献类型：
--
作者：
Pickering, John W.;Frampton, Christopher M.;Endre, Zoltan H.
背景和目的：急性肾损伤（阿基）的临床试验使用肌酐变化作为结局指标。本研究调查了结果指标和基线肌酐如何影响试验outcome.Design，设置，参与者和测量：一个一室药代动力学模型的肌酐变化导致的GFR下降被应用到一个人口的10,000模拟虚拟住院病人。将治疗模拟为GFR降低改善特定百分比，即治疗疗效（50%）。三个分类和两个连续的结果指标进行了计算和比较。比较了测量的和估计的基线肌酸酐水平的结果，这些水平是假设GFR为100或75 ml/min而反算的。结果：连续指标、肌酸酐平均值和相对于基线的肌酸酐平均值随着治疗效果的增加而大致线性下降。分类指标显示S形下降，当GFR下降仅改善60 - 80%时，错误地提示完美治疗。使用基线肌酐的估计值增加了被归类为阿基.Conclusions的患者数量：当用于确定临床试验结果时，连续指标正确检测干预程度。在低疗效时，分类指标低估了治疗效果，而在高疗效时高估了治疗效果。当人群中包含较高比例的更严重阿基患者时，这些影响被夸大。与测量的基线值相比，估计的基线肌酐水平将高估阿基患病率。阿基的临床试验应使用连续的结局指标和测量的基线，并报告基线中位数和四分位距。Chit J Ant Soc Nephrol 4：1705-1715，2009. doi：10.2215/CJN.00820209
Background and objectives: Clinical trials of acute kidney injury (AKI) use changes in creatinine as outcome metrics. This study investigated how outcome metrics and baseline creatinine affect trial outcome.Design, setting, participants, & measurements: A one-compartment pharmacokinetic model of creatinine change resulting from a decrease in GFR was applied to a population of 10,000 simulated virtual inpatients. Treatment was simulated as an amelioration of GFR decrease by a specified percentage, the treatment efficacy, in 50%. Three categorical and two continuous outcome metrics were calculated and compared. Outcomes were compared for measured and estimated baseline creatinine levels that were back-calculated assuming a GFR of 100 or 75 ml/min.Results: The continuous metrics, the average value of creatinine and the average value of creatinine relative to baseline decreased approximately linearly with increase in treatment efficacy. The categorical metrics displayed a sigmoidal decrease and erroneously suggested perfect treatment when GFR decrease was ameliorated by only 60 to 80%. Using an estimate of baseline creatinine increased the number of patients who were classified as having AKI.Conclusions: When used to determine clinical trial outcome, continuous metrics correctly detected the extent of intervention. At low treatment efficacy, categorical metrics underestimated and at high treatment efficacy overestimated the effect of treatment. These effects were exaggerated when the population contained a high proportion of patients with more severe AKI. An estimated baseline creatinine level will overestimate AKI prevalence compared with a measured baseline value. Clinical trials of AKI should use a continuous outcome metric and a measured baseline and report baseline median and interquartile range. Chit J Ant Soc Nephrol 4: 1705-1715, 2009. doi: 10.2215/CJN.00820209