Article

Handling of baseline covariates in randomized controlled trials: a review of trials published in leading medical journals

Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Journal of clinical epidemiology (Impact Factor: 5.48). 09/2009; 63(2):142-53. DOI: 10.1016/j.jclinepi.2009.06.002
Source: PubMed

ABSTRACT Statisticians have criticized the use of significance testing to compare the distribution of baseline covariates between treatment groups in randomized controlled trials (RCTs). Furthermore, some have advocated for the use of regression adjustment to estimate the effect of treatment after adjusting for potential imbalances in prognostically important baseline covariates between treatment groups.
We examined 114 RCTs published in the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, and the British Medical Journal between January 1, 2007 and June 30, 2007.
Significance testing was used to compare baseline characteristics between treatment arms in 38% of the studies. The practice was very rare in British journals and more common in the U.S. journals. In 29% of the studies, the primary outcome was continuous, whereas in 65% of the studies, the primary outcome was either dichotomous or time-to-event in nature. Adjustment for baseline covariates was reported when estimating the treatment effect in 34% of the studies.
Our findings suggest the need for greater editorial consistency across journals in the reporting of RCTs. Furthermore, there is a need for greater debate about the relative merits of unadjusted vs. adjusted estimates of treatment effect.

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Questions & Answers about this publication

  • Eik Vettorazzi added an answer in Systematic Reviews:
    What is the main advantage of using the "mean differences adjusted for baseline" over the commonly used "mean differences" to analyze effect size?
    My question adresses specifically continuous variables. When does the first method is indicated over the second? When is it counter-indicated? How to calculate it? Can I calculate it on RevMan?
    Eik Vettorazzi · University Medical Center Hamburg - Eppendorf
    Are both effect measures available in all studies? If so, then fortunately a lot changed since the reviews of Altman and Doré (1990)
    http://www.sciencedirect.com/science/article/pii/014067369090014V
    and Austin et al (2009) https://www.researchgate.net/publication/26776077_A_substantial_and_confusing_variation_exists_in_handling_of_baseline_covariates_in_randomized_controlled_trials_a_review_of_trials_published_in_leading_medical_journals
    Then according to Stephen Senn (see above) the adjusted estimate is unbiased and more efficient.
  • Eik Vettorazzi added an answer in Statistical Analysis:
    Is there sense in using inferential statistics to assess baseline comparability in an RCT?
    Inferential statistics are essential for estimating likely population effects from sample data. But are they useful for comparing groups for baseline comparability?
    Eik Vettorazzi · University Medical Center Hamburg - Eppendorf
    To second Leventes nice comment, Austin et al accomplished a review of the usual practice in reporting RCTs, with interesting country-specific approaches.
    https://www.researchgate.net/publication/26776077_A_substantial_and_confusing_variation_exists_in_handling_of_baseline_covariates_in_randomized_controlled_trials_a_review_of_trials_published_in_leading_medical_journals

    And I find the article from Stephen Senn also helpful.
    https://www.researchgate.net/publication/15200947_Testing_for_baseline_balance_in_clinical_trials