Ideal vs. real: a systematic review on handling covariates in randomized controlled trials

BMC Medical Research Methodology

  ^{1    2    2    3    4} 

[1] 0000 0001 2299 3507, grid.16753.36, Department of Preventive Medicine, Biostatistics Collaboration Center, Feinberg School of Medicine, Northwestern University, 680 N Lake Shore Drive, Suite 1400, 60611-4402, Chicago, IL, USA;0000 0004 0572 4227, grid.431072.3, AbbVie Inc, North Chicago, IL, USA;0000 0004 1936 8753, grid.137628.9, Department of Population Health, New York University Langone Health, New York, NY, USA;AY analytics, Chicago, IL, USA;

关键词: Randomization;    Allocation;    Stratification;    Minimization;    CONSORT;   

DOI  :  10.1186/s12874-019-0787-8

来源: publisher

【 摘 要 】

BackgroundIn theory, efficient design of randomized controlled trials (RCTs) involves randomization algorithms that control baseline variable imbalance efficiently, and corresponding analysis involves pre-specified adjustment for baseline covariates. This review sought to explore techniques for handling potentially influential baseline variables in both the design and analysis phase of RCTs.MethodsWe searched PubMed for articles indexed “randomized controlled trial”, published in the NEJM, JAMA, BMJ, or Lancet for two time periods: 2009 and 2014 (before and after updated CONSORT guidelines). Upon screening (343), 298 articles underwent full review and data abstraction.ResultsTypical articles reported on superiority (86%), multicenter (92%), two-armed (79%) trials; 81% of trials involved covariates in the allocation and 84% presented adjusted analysis results. The majority reported a stratified block method (69%) of allocation, and of the trials reporting adjusted analyses, 91% were pre-specified. Trials published in 2014 were more likely to report adjusted analyses (87% vs. 79%, p = 0.0100) and more likely to pre-specify adjustment in analyses (95% vs. 85%, p = 0.0045). Studies initiated in later years (2010 or later) were less likely to use an adaptive method of randomization (p = 0.0066; 7% of those beginning in 2010 or later vs. 31% of those starting before 2000) but more likely to report a pre-specified adjusted analysis (p = 0.0029; 97% for those initiated in 2010 or later vs. 69% of those started before 2000).ConclusionWhile optimal reporting procedures and pre-specification of adjusted analyses for RCTs tend to be progressively more prevalent over time, we see the opposite effect on reported use of covariate-adaptive randomization methods.

【 授权许可】

CC BY