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.


METHODS
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.
Austin
Peter C
PC
Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. peter.austin@ices.on.ca
Manca
Andrea
A
Zwarenstein
Merrick
M
Juurlink
David N
DN
Stanbrook
Matthew B
MB
D000704:Analysis of Variance; D003627:Data Interpretation, Statistical; D006801:Humans; D010506:Periodicals as Topic / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome