title: How many patients? How many limbs? Analysis of patients or limbs in the orthopaedic literature: a systematic review.
abstract: BACKGROUND
  Clinical studies assessing orthopaedic interventions often include data from two limbs or multiple joints within single individuals. Without appropriate design or statistical approaches to address within-individual correlations, this practice may contribute to false precision and possible bias in estimates of treatment effect. We conducted a systematic review of the orthopaedic literature to determine the frequency of inappropriate inclusion of nonindependent limb or joint observations in clinical studies.
  
  
  METHODS
  We identified seven orthopaedic journals with high Science Citation Index impact factors and retrieved all clinical studies for 2003 for any intervention on any limb or joint.
  
  
  RESULTS
  We identified 288 clinical studies, 143 of which involved two limbs or multiple joint observations from single individuals. These studies included nineteen randomized clinical trials (13%) fifty-eight two-group cohort studies (41%), and sixty-six one-group cohort studies (46%). Seventy-six (53%) of the 143 studies involved statistical comparisons between patient groups with use of tests of association, and an additional sixty studies (42%) presented estimates of proportions without statistical comparisons. Only sixteen of the seventy-six studies involving statistical comparisons involved the use of any technique or methodological approach to account for multiple, nonindependent observations. A median of approximately 13% of the patients in these studies contributed more than one observation. The median proportion of nonindependent observations to total observations (the unit of analysis) was approximately 23%.
  
  
  CONCLUSIONS
  Our findings suggest that a high proportion (42%) of clinical studies in high-impact-factor orthopaedic journals involve the inappropriate use of multiple observations from single individuals, potentially biasing results. Orthopaedic researchers should attend to this issue when reporting results.
authors.affiliation: Faculty of Health Sciences, The University of Western Ontario, Elborn College Room 1438, London, ON N6G 1H1, Canada. dianne.bryant@uwo.ca
authors.forename: Dianne
authors.initials: D
authors.lastname: Bryant
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Havey
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D015982:Bias; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005121:Extremities; D006801:Humans; D007596:Joints; D009985:Orthopedics; D010361:Patients; D016032:Randomized Controlled Trials as Topic; D012107:Research Design