Reprint of "Influence of analytical bias and imprecision on the number of false positive results using Guideline-Driven Medical Decision Limits".
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".


TERMS
Effects of analytical bias and imprecision should be investigated separately and analytical quality specifications should be estimated accordingly.


BIOLOGICAL VARIATION AND ANALYTICAL PERFORMANCE
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.


FREQUENCY OF FOLLOW-UP LABORATORY TESTS
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.


PROBABILITY FUNCTION FOR DIAGNOSES
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.
['Hyltoft Petersen|Per|P|', 'Klee|George G|GG|']
D015982:Bias D019411:Clinical Laboratory Techniques 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
Analytical bias Analytical quality specifications Probability function Analytical imprecision Clinical guidelines Clinical outcome