Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis
Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis
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DOI：
10.1136/bmj.e5840
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发表时间：
2012-09-14
影响因子：
105.7
通讯作者：
Morris, Tim P.
中科院分区：
文献类型：
--
作者：
Kahan, Brennan C.;Morris, Tim P.
目的评估分层随机化的使用频率，分析是否对所有平衡变量进行了调整，以及随机化方法是否得到了充分的报道，并重新分析先前报道的试验，以评估在分析中忽略平衡因素的影响。设计回顾已发表的试验和重新分析先前报道的试验。（BMJ，Journal of the American Medical Association，Lancet，and新英格兰医学杂志）和第二次多中心胸膜内脓毒症试验（MIST 2）。参与者258项试验于2010年发表在四种期刊上。排除了整群随机、交叉、非随机、单组和I期或II期试验，也排除了报告次要分析、中期分析或先前在2010年发表的结果的试验。结果对MIST 2的再分析显示，未调整的分析导致P值增大，把握度降低。对已发表试验的回顾表明，平衡随机化很常见，163项试验（63%）使用至少一个平衡变量。最常见的平衡方法是分层排列区组（n=85）和最小化（n=27）。在37%的试验中，随机化方法不清楚。大多数平衡中心或预后因素的试验没有得到充分分析;只有26%的试验在主要分析中调整了所有平衡因素。没有调整平衡因素的试验在他们的分析是不太可能显示出统计学上显着的结果（未调整57%v调整78%，P=0.02）。结论平衡中心或预后因素是常见的试验，但往往描述不佳，平衡的影响是知之甚少。试验者应调整其主要分析以平衡因素，以获得正确的P值和置信区间，并避免不必要的功效损失。
Objectives To assess how often stratified randomisation is used, whether analysis adjusted for all balancing variables, and whether the method of randomisation was adequately reported, and to reanalyse a previously reported trial to assess the impact of ignoring balancing factors in the analysis.Design Review of published trials and reanalysis of a previously reported trial.Setting Four leading general medical journals (BMJ, Journal of the American Medical Association, Lancet, and New England Journal of Medicine) and the second Multicenter Intrapleural Sepsis Trial (MIST2).Participants 258 trials published in 2010 in the four journals. Cluster randomised, crossover, non-randomised, single arm, and phase I or II trials were excluded, as were trials reporting secondary analyses, interim analyses, or results that had been previously published in 2010.Main outcome measures Whether the method of randomisation was adequately reported, how often balanced randomisation was used, and whether balancing factors were adjusted for in the analysis.Results Reanalysis of MIST2 showed that an unadjusted analysis led to larger P values and a loss of power. The review of published trials showed that balanced randomisation was common, with 163 trials (63%) using at least one balancing variable. The most common methods of balancing were stratified permuted blocks (n=85) and minimisation (n=27). The method of randomisation was unclear in 37% of trials. Most trials that balanced on centre or prognostic factors were not adequately analysed; only 26% of trials adjusted for all balancing factors in their primary analysis. Trials that did not adjust for balancing factors in their analysis were less likely to show a statistically significant result (unadjusted 57% v adjusted 78%, P=0.02).Conclusion Balancing on centre or prognostic factors is common in trials but often poorly described, and the implications of balancing are poorly understood. Trialists should adjust their primary analysis for balancing factors to obtain correct P values and confidence intervals and to avoid an unnecessary loss in power.