Uncertainty tolerance validation

In deciding on uncertainty tolerances the fitness for purpose criterion becomes crucially important. For example, when developing and validating a bioanalytical method, if the achievable accuracy and precision lead the analyst to conclude that the current method is not suitable relative to the original assay requirements, the method in its current form might be discarded altogether, used as the basis for further development of a method that does satisfy the specific criteria, and/or retained as a useful method that can be applied to studies conducted in a less demanding environment. 

The previous sections in this chapter addressed the process of validating the method and documenting the results in a final validation report. When reviewing the analytical data for the study samples the validation report and associated tables and supporting documentation must be carefully reviewed for accuracy and scientific content, to ensure that the necessary experiments have been run and that the data supports the original uncertainty tolerances (Section 9.3). In addition to the validation report, the final method must be reviewed and approved for sample analysis. Specific acceptance criteria that will be used during sample analysis should be documented in the approved method or equivalent SOP. 

Next, the applications have to be validated and placed into standardized forms. Validation should consist of two steps. First, simulated data sets of aerosol properties should be generated from pre-selected source contributions as did Watson in his simulation studies of the chemical mass balance method. These data should be perturbed with the types of uncertainties expected under field conditions. The types of sources and their contributions predicted by the receptor model application should be compared with the known source model values and the extent of perturbation tolerable should be assessed. 

Examples for reference materials useful for instrument calibration, method validation and development in the field of human materials for which certified or other kinds of concentration values are reported for the 13 trace elements considered in this book (Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V and Zn) are given in Table 3. The data are taken from the survey prepared by Cortes Toro et al. (1990) and from other sources (BCR, 1992, Trahey, 1992, Chai Chifang, 1993) which the reader should consult for further details. Most of the columns are self explanatory. Column T contains a code (C = certified, N = noncertified or information value) for the type of reference value specified by the issuing authority. The uncertainty in the concentration value is expressed as a percentage error, but the meaning of this may differ somewhat from one material to another. In most cases it expresses the 95% confidence interval of the mean, but in a few other cases a tolerance interval, or some other definition (sometimes unspecified), may have been used by the producer. 

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