The “Top-Down” method

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

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)

Move on to the G.U.M. approach

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