title: Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials.
abstract: Published evidence suggests that aspects of trial design lead to biased intervention effect estimates, but findings from different studies are inconsistent. This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials. Outcome measures were classified as "mortality," "other objective," "or subjective," and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity. Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear (vs. adequate) random-sequence generation (ratio of odds ratios, 0.89 [95% credible interval {CrI}, 0.82 to 0.96]) and with inadequate or unclear (vs. adequate) allocation concealment (ratio of odds ratios, 0.93 [CrI, 0.87 to 0.99]). Lack of or unclear double-blinding (vs. double-blinding) was associated with an average of 13% exaggeration of intervention effects (ratio of odds ratios, 0.87 [CrI, 0.79 to 0.96]), and between-trial heterogeneity was increased for such studies (SD increase in heterogeneity, 0.14 [CrI, 0.02 to 0.30]). For each characteristic, average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jelena
authors.initials: J
authors.lastname: Savović
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Jones
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Harris
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.forename: Julie
authors.initials: J
authors.lastname: Pildal
authors.forename: Bodil
authors.initials: B
authors.lastname: Als-Nielsen
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Balk
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Gluud
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Schulz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Beynon
authors.forename: Nicky J
authors.initials: NJ
authors.lastname: Welton
authors.forename: Lesley
authors.initials: L
authors.lastname: Wood
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Deeks
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D004311:Double-Blind Method; D006801:Humans; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design