title: Reprint of "Influence of analytical bias and imprecision on the number of false positive results using Guideline-Driven Medical Decision Limits".
abstract: BACKGROUND
  Diagnostic decisions based on decision limits according to medical guidelines are different from the majority of clinical decisions due to the strict dichotomization of patients into diseased and non-diseased. Consequently, the influence of analytical performance is more critical than for other diagnostic decisions where much other information is included. The aim of this opinion paper is to investigate consequences of analytical quality and other circumstances for the outcome of "Guideline-Driven Medical Decision Limits".
  Effects of analytical bias and imprecision should be investigated separately and analytical quality specifications should be estimated accordingly.
  Use of sharp decision limits doesn't consider biological variation and effects of this variation are closely connected with the effects of analytical performance. Such relationships are investigated for the guidelines for HbA1c in diagnosis of diabetes and in risk of coronary heart disease based on serum cholesterol. The effects of a second sampling in diagnosis give dramatic reduction in the effects of analytical quality showing minimal influence of imprecision up to 3 to 5% for two independent samplings, whereas the reduction in bias is more moderate and a 2% increase in concentration doubles the percentage of false positive diagnoses, both for HbA1c and cholesterol.
  An alternative approach comes from the current application of guidelines for follow-up laboratory tests according to clinical procedure orders, e.g. frequency of parathyroid hormone requests as a function of serum calcium concentrations. Here, the specifications for bias can be evaluated from the functional increase in requests for increasing serum calcium concentrations.
  In consequence of the difficulties with biological variation and the practical utilization of concentration dependence of frequency of follow-up laboratory tests already in use, a kind of probability function for diagnosis as function of the key-analyte is proposed.
authors.affiliation: The Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Section for General Practice, Department of Public Health and Primary Health Care, Faculty of Medicine and Dentistry, University of Bergen, Norway. Electronic address: Per.Petersen@isf.uib.no.
authors.forename: Per
authors.initials: P
authors.lastname: Hyltoft Petersen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Klee
mesh_terms: D015982:Bias; D019411:Clinical Laboratory Techniques / Q000379:methods* / Q000592:standards; D005189:False Positive Reactions; D006801:Humans; D057230:Limit of Detection; D017410:Practice Guidelines as Topic; D011336:Probability; D011785:Quality Assurance, Health Care; D012016:Reference Values; D015203:Reproducibility of Results; D012107:Research Design
keywords: Analytical bias; Analytical imprecision; Analytical quality specifications; Clinical guidelines; Clinical outcome; Probability function