title: The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials.
abstract: OBJECTIVE
  To summarise comparisons of randomised clinical trials and non-randomised clinical trials, trials with adequately concealed random allocation versus inadequately concealed random allocation, and high quality trials versus low quality trials where the effect of randomisation could not be separated from the effects of other methodological manoeuvres.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Cohorts or meta-analyses of clinical trials that included an empirical assessment of the relation between randomisation and estimates of effect.
  
  
  METHODS
  Cochrane Review Methodology Database, Medline, SciSearch, bibliographies, hand searching of journals, personal communication with methodologists, and the reference lists of relevant articles.
  
  
  METHODS
  Relation between randomisation and estimates of effect.
  
  
  RESULTS
  Eleven studies that compared randomised controlled trials with non-randomised controlled trials (eight for evaluations of the same intervention and three across different interventions), two studies that compared trials with adequately concealed random allocation and inadequately concealed random allocation, and five studies that assessed the relation between quality scores and estimates of treatment effects, were identified. Failure to use random allocation and concealment of allocation were associated with relative increases in estimates of effects of 150% or more, relative decreases of up to 90%, inversion of the estimated effect and, in some cases, no difference. On average, failure to use randomisation or adequate concealment of allocation resulted in larger estimates of effect due to a poorer prognosis in non-randomly selected control groups compared with randomly selected control groups.
  
  
  CONCLUSIONS
  Failure to use adequately concealed random allocation can distort the apparent effects of care in either direction, causing the effects to seem either larger or smaller than they really are. The size of these distortions can be as large as or larger than the size of the effects that are to be detected.
authors.affiliation: Department of Nephrology, Charité, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kunz
authors.forename: A D
authors.initials: AD
authors.lastname: Oxman
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003625:Data Collection; D011786:Quality Control; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards; D015983:Selection Bias