Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study.
Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study.
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DOI：
10.1136/bmj.f457
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发表时间：
2013-01-29
期刊：
影响因子：
--
通讯作者：
Taylor RS
中科院分区：
文献类型：
--
作者：
Ciani O;Buyse M;Garside R;Pavey T;Stein K;Sterne JA;Taylor RS
目的量化并比较报告生物标志物或中间结局（替代结局）的试验与使用最终患者相关主要结局的试验的治疗效果和偏倚风险。设计元流行病学研究。数据来源：2005年和2006年发表在六种高影响力医学期刊上的所有随机临床试验：Annals of Internal Medicine，BMJ，Journal of the American Medical Association，Lancet，新英格兰医学杂志和PLoS Medicine。研究选择两名独立的评审员选择试验。根据预定义的表格记录试验特征、偏倚风险和结局。两名评审员独立检查数据提取。比值比用于量化使用替代结局的试验与使用患者相关结局的试验之间治疗效果的差异程度，也根据试验特征进行了调整。比值比>1.0意味着具有替代结局的试验比具有患者相关结局的试验报告了更大的干预效应。结果84篇使用替代结局的试验和101篇使用患者相关结局的试验被纳入分析。除了中位样本量（371 v741）和单中心状态（23% v9%）外，使用替代结局的试验和使用患者相关结局的试验的研究特征平衡良好。他们的偏见风险没有区别。主要分析显示，报告替代终点的试验具有更大的治疗效果（比值比0.51，95%置信区间0.42 - 0.60），而不是报告患者相关结局的试验（0.76，0.70至0.82），未校正比值比为1.47（1.07至2.01），校正比值比为1.46（1.05至2.04）。该结果在敏感性和次要分析中一致。结论报告替代主要结局的试验比报告最终患者相关主要结局的试验更可能报告更大的治疗效果。这一发现不能用两组试验的偏倚风险或特征的差异来解释。
Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.
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DOI：
10.1136/bmj.e813
发表时间：
2012-02-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Bafeta A;Dechartres A;Trinquart L;Yavchitz A;Boutron I;Ravaud P
通讯作者：
Ravaud P
影响因子：
45.3
作者：
Giaccone, G;Herbst, RS;Johnson, DH
通讯作者：
Johnson, DH
影响因子：
45.3
作者：
Buyse, Marc;Burzykowski, Tomasz;Piedbois, Pascal
通讯作者：
Piedbois, Pascal
影响因子：
168.9
作者：
Chan, AW;Altman, DG
通讯作者：
Altman, DG
影响因子：
39.2
作者：
Dechartres, Agnes;Boutron, Isabelle;Ravaud, Philippe
通讯作者：
Ravaud, Philippe