title: Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies.
abstract: BACKGROUND
  Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions.
  
  
  METHODS
  We targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies.
  
  
  RESULTS
  Eligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did.
  
  
  CONCLUSIONS
  Nonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies.
authors.affiliation: Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Panagiotis N
authors.initials: PN
authors.lastname: Papanikolaou
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Christidi
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D015982:Bias; D064420:Drug-Related Side Effects and Adverse Reactions; D016021:Epidemiologic Studies; D019317:Evidence-Based Medicine; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012306:Risk; D013514:Surgical Procedures, Operative / Q000009:adverse effects; D014612:Vaccines / Q000009:adverse effects; D014815:Vitamins / Q000009:adverse effects
chemical_list: D014612:Vaccines; D014815:Vitamins