title: Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.
abstract: OBJECTIVE
  To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects.
  
  
  METHODS
  An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects.
  
  
  METHODS
  Meta-analyses from the Cochrane Pregnancy and Childbirth Database.
  
  
  METHODS
  The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding.
  
  
  RESULTS
  Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%.
  
  
  CONCLUSIONS
  This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.
authors: Division of STD/HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333.
authors: K F
authors: KF
authors: Schulz
authors: I
authors: I
authors: Chalmers
authors: R J
authors: RJ
authors: Hayes
authors: D G
authors: DG
authors: Altman
mesh_terms: D015982:Bias; D002985:Clinical Protocols; D015233:Models, Statistical; D011786:Quality Control; D016032:Randomized Controlled Trials as Topic / Q000592:standards* / Q000706:statistics & numerical data; D012107:Research Design