Clinical decision limits as criteria for setting analytical performance specifications for laboratory tests

The biological (CV_I), preanalytical (CV_PRE), and analytical variation (CV_A) are inherent to clinical laboratory testing and consequently, interpretation of clinical test results.

The sum of the CV_I, CV_PRE, and CV_A, called diagnostic variation (CV_D), was used to derive clinically acceptable analytical performance specifications (CAAPS) for clinical chemistry measurands. The reference change concept was applied to clinically significant differences (CD) between two measurements, with the formula CD = z*√2* CV_D. CD for six measurands were sought from international guidelines. The CAAPS were calculated by subtracting variances of CV_I and CV_PRE from CV_D. Modified formulae were applied to consider statistical power (1-β) and repeated measurements.

The obtained CAAPS were 44.9% for urine albumin, 0.6% for plasma sodium, 22.9% for plasma pancreatic amylase, and 8.0% for plasma creatinine (z = 3, α = 2.5%, 1-β = 85%). For blood HbA_1c and plasma low-density lipoprotein cholesterol, replicate measurements were necessary to reach CAAPS for patient monitoring. The derived CAAPS were compared with analytical performance specifications, APS, based on biological variation.

The CAAPS models pose a new tool for assessing APS in a clinical laboratory. Their usability depends on the relevance of CD limits, required statistical power and the feasibility of repeated measurements.