Youden pairs

For a full validation trial a minimum of 8 laboratories is recommended, although 15 is considered ideal for establishing reproducibility. Because most methods are used over a range of concentrations, at least five or six samples of concentrations that span the expected range should be analyzed. Duplicate samples should be sent to the laboratories, with either the same concentration or slightly different concentrations ( Youden pairs ). 

The evaluation study will determine the attributes (bias, precision, specificity, limits of detection) of the immunoassay. Bias testing (systematic error) will be conducted by measuring recoveries of the analyte added to matrices of interest. Replicate analysis will be performed on blind replicates or split levels (e.g., Youden pairs). A minimum number of replicates will be performed to provide statistically meaningful results. The number of replicates will be determined by the intended purpose of the immunoassay as well as the documented method performance of the comparative method. 

The example demonstrates that all relevant information must be used ignoring the fact that the PM and HPLC measurements for / = 1. .. 5 are paired results in a loss of information. The paired data should under all circumstances be plotted (Youden plot. Fig. 2.1, and Fig. 1.23) to avoid a pitfall it must be borne in mind that the paired r-test yields insights only for the particular (addi-... 

After many years of debate and discussion, there is now an international consensus about the statistical approach and method to be employed in full collaborative trials This topic is discussed further in Section 9.5. The lUPAC protocol referred to above requires the analysis of duplicate test samples of the same material (a minimum of five materials or, exceptionally, three) in eight or more laboratories. However, there are many occasions where inter-laboratory studies are needed which, for various reasons, cannot achieve the prescribed criteria. In instances where the lUPAC criteria cannot be achieved, it is recommended that the Youden Matched Pairs procedure is used. The statistics of the method have been recently updated and a new procedure described. 

The calculations for the Youden matched pairs procedure are less complicated than those for the lUPAC protocol and do not involve outlier detection and removal. For the example, the results are shown in Table 27. 

Table 27 Basic calculations for the Youden matched pairs procedure...

Table 28 General ANOVA table for Youden matched pairs for S samples and L laboratories...

A reference method is one which after exhaustive investigation has been shown to have negligible inaccuracy in comparison with its imprecision [International Federation of Clinical Chemistry (IFCC), 1979]. With its comparison of inaccuracy and imprecision this definition clearly refers to the principles of quality control in clinical chemistry. Indeed, statistical models such as Youden plots are used to find out whether the error in a pair of results happens by chance (imprecision of the method) or is systematic (inaccuracy) (Youden, 1967). If the results are close to the true values, inaccuracy is negligible in comparison with imprecision. As demonstrated earlier, each analytical procedure has a certain degree of imprecision consequently, the total absence of systematic error can never be proved. Only as the influence of a systematic error is evident in comparison with the influence of chance or random error can the systematic error be demonstrated. 

Analysis of systematic errors in the determination of hydrocarbons in water can be achieved by use of Youden plots after transformation of the results to an overall mean of Mtotal=0 and a standard deviation of Stotal=l (Fig. 3). Almost all laboratories are distributed around the 45° line indicating that most of the variation was systematic rather than random, particularly at higher mineral oil concentrations (sample pair S2/S4, Fig. 3B). Results located within the interval Mtotal 2 Stotal indicate sufficient proficiency of the participating laboratories in performing the determination of hydrocarbons in water... 

Fig. 3 Youden plot of the results (transformed to an overall mean of Mtotal=0 and a standard deviation of Stotal=l) for sample pair S1/S3 (A) and sample pair S2/S4 (B). Satisfactory performance is represented by the displayed box (Mtotal 2 Stotal). Each dot represents the results of an individual laboratory marked by a letter code ( - laboratories involved in PLC-4)...

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