A substantial and confusing variation exists in handling of baseline covariates in randomized controlled trials: a review of trials published in leading medical journals.

OBJECTIVE

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.

STUDY DESIGN AND SETTING

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.

RESULTS

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.

CONCLUSIONS

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.