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

Jody D. Ciolino*, Hannah L. Palac, Amy Yang, Mireya Vaca, Hayley M. Belli

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Background: In 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. Methods: We 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. Results: Typical 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). Conclusion: While 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.

Original languageEnglish (US)
Article number136
JournalBMC Medical Research Methodology
Volume19
Issue number1
DOIs
StatePublished - Jul 3 2019

Keywords

  • Allocation
  • CONSORT
  • Minimization
  • Randomization
  • Stratification

ASJC Scopus subject areas

  • Epidemiology
  • Health Informatics

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