Imprecision Uncertainty (Uprec)
The random effects of the entire procedure over a defined period of time are termed the Imprecision Uncertainty. For top-down (Type A) analysis, IQC controls of two levels across the clinically relevant range for analysis are used. Where > 2 levels are available they are incorporated into the calculation as seen below.
Imprecision uncertainty 2 = ((SDL1)2*(nL1-1) + (SDL2)2*(nL2-1)) / (nL1 + nL2) – 2
Where n = number of IQC data points
SD = standard deviation
L1/L2 = IQC Levels 1 and 2
The result from this calculation provides the Imprecision Uncertainty which itself is reported and is also used for further calculations.
Bias of measurement and associated uncertainty
Both a determination of assay bias and the uncertainty of the reference value (when available) are combined to provide the bias uncertainty as below:
Bias uncertainty = ((Reference bias2) + (Assay bias/SEM2))1/2
Where SEM = Standard Error of the Mean.
Significant Assay Bias (>10% of the Imprecision Uncertainty) is recommended to first be removed by recalibration and if still present entered into the overall calculation of combined MU. Bias significance is determined by a one sample t-test where:
t = Bias/ bias uncertainty
Where t is compared to the 95% critical t value.
If t > critical tbias it is considered to be significant.
Although recommendations are not to include assay bias if present at <10% of the Imprecision Uncertainty, the decision has been made to include all sources of uncertainty in the final calculation and reported MU.
Combined Uncertainty = (Bias uncertainty2 + Imprecision Uncertainty2)1/2
For a full, excellent description of this process refer to:
Technical Guide 4 – A Guide on Measurement Uncertainty in Medical Testing (Feb 2013 – Singapore accreditation council)