Assessing the Validity of Surrogate Outcomes for ESRD: A Meta-Analysis
Assessing the Validity of Surrogate Outcomes for ESRD: A Meta-Analysis
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DOI：
10.1681/asn.2014040396
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发表时间：
2015-09-01
影响因子：
13.6
通讯作者：
Hemmelgarn, Brenda R.
中科院分区：
文献类型：
--
作者：
Jun, Min;Turin, Tanvir Chowdhury;Hemmelgarn, Brenda R.
在随机对照试验（RCT）中，对ESRD当前和有希望的替代结局的验证有限。我们对随机对照试验进行了系统回顾和荟萃分析，以进一步了解替代结局预测各种干预措施对终末期肾病疗效的能力。检索了MEDLINE、EMBASE和CENTRAL（从开始到2013年9月）。纳入了在1年随访期间报告ESRD事件和ESRD替代结局（蛋白尿变化或血清肌酐加倍[DSCR]）的蛋白尿、糖尿病或1-4期CKD成人或肾移植受者中的所有RCT。两名评价者独立提取试验特征和结局数据。为了评估替代结局与ESRD之间的相关性，我们确定了治疗效果比（TER），定义为对ESRD的治疗效果与对替代结局变化的影响的比值。TER接近1表明ESRD和替代品之间的一致性更高，并且这些比率在干预措施中合并。我们确定了27项试验（97，458名参与者; 4187名ESRD参与者）。7项试验报告了对蛋白尿变化的影响，并显示了对蛋白尿和ESRD的一致影响（TER，0.82; 95%置信区间，0.59至1.16），异质性最小。DSCR报告了20项试验。对DSCR的治疗效果与对ESRD的效果一致（TER，0.98; 95%置信区间，0.85 - 1.14），具有中度异质性。总之，DSCR通常是ESRD的良好替代物，而蛋白尿的数据有限。进一步评估蛋白尿的替代使用前瞻性随机对照试验是必要的。
Validation of current and promising surrogate outcomes for ESRD in randomized controlled trials (RCTs) has been limited. We conducted a systematic review and meta-analysis of RCTs to further inform the ability of surrogate outcomes for ESRD to predict the efficacy of various interventions on ESRD. MEDLINE, EMBASE, and CENTRAL (from inception through September 2013) were searched. All RCTs in adults with proteinuria, diabetes, or CKD stages 1-4 or renal transplant recipients reporting ESRD events and a surrogate outcome (change in proteinuria or doubling of serum creatinine [DSCR]) for ESRD during a year follow-up were included. Two reviewers abstracted trial characteristics and outcome data independently. To assess the correlation between the surrogate outcomes and ESRD, we determined the treatment effect ratio (TER), defined as the ratio of the treatment effects on ESRD and the effects on the change in surrogate outcomes. TERs close to 1 indicate greater agreement between ESRD and the surrogate, and these ratios were pooled across interventions. We identified 27 trials (97,458 participants; 4187 participants with ESRD). Seven trials reported the effects on change in proteinuria and showed consistent effects for proteinuria and ESRD (TER, 0.82; 95% confidence interval, 0.59 to 1.16), with minimal heterogeneity. Twenty trials reported on DSCR. Treatment effects on DSCR were consistent with the effects on ESRD (TER, 0.98; 95% confidence interval, 0.85 to 1.14), with moderate heterogeneity. In conclusion, DSCR is generally a good surrogate for ESRD, whereas data on proteinuria were limited. Further assessment of the surrogacy of proteinuria using prospective RCTs is warranted.