title: Weak associations between prognostic biomarkers and disease in preliminary studies illustrates the breach between statistical significance and diagnostic discrimination.
abstract: BACKGROUND
  Prior to actual well-designed outcome studies, statistical significance does not imply diagnostic usefulness. Sensitivity/specificity graphs have been a mainstay in evaluating potential diagnostic usefulness. Unfortunately, many recent studies have been expressed as relative risk (RR) or odds ratios (OR) based on statistical significance that produces misleading constructs, especially when the relationship between the biomarker and disease is weak. The purpose of this review is to discuss the meaning of the diagnostic relationships when the association between a biomarker and a disease is weak such that it shows poor discrimination by sensitivity/specificity plots.
  
  
  METHODS
  Review of the literature, illustrative example and calculation of positive predictive values.
  
  
  RESULTS
  Information from the literature showing the equivalency between OR and sensitivity/specificity plots and defining weak diagnostic discrimination. Demonstration of how confounders can alter between study statistical significance when there is a weak diagnostic relationship.
  
  
  CONCLUSIONS
  RR or OR should be expressed as diagnostic sensitivity/specificity plots. Usually predictive values will identify whether or not there is potential diagnostic value that is economically reasonable. Very weak diagnostic relationships produce very low positive predictive values. Great caution should be exercised when considering weak associations for diagnostic use, especially if the biomarker is not a modifiable risk factor.
authors.affiliation: Department of Veterans Affairs Medical Center, Louisville, KY 40206, United States. levinson@louisville.edu
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Levinson
mesh_terms: D015415:Biomarkers / Q000032:analysis; D003627:Data Interpretation, Statistical; D004194:Disease; D006801:Humans; D016017:Odds Ratio; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers