Table 2 Analytical methods Statistical analysis We followed the

Table 2. Analytical methods Statistical analysis We followed the definitions and procedures outlined in International Standardization Organization (ISO) documents (ISO 5725-1, ISO 5725-2, and ISO 5725-4) except SB203580 p38 MAPK inhibitor as indicated below. The first and last of these documents define trueness to describe the closeness of agreement between the arithmetic mean of a large number of test results and the true or accepted reference values (our targets for the pools in Table 1). Precision refers to the closeness of agreement between test results. An estimate of bias from an assessing laboratory is the difference between the mean of the pool target concentration and its accepted target reference value. To assess the significance of the bias estimates, we constructed 95% CIs around this difference, using equations from section 4.

7.2 in ISO 5725-4:1994(E). No significant bias was declared if the interval covered the value 0. Other concepts in the context of laboratory testing include repeatability, which characterizes variability among replicates obtained in the same laboratory on the same material (target concentration), and the between-laboratory variance, which refers to variability among laboratories using the same method. We used the approach outlined in ISO 5725-2:1994(E) to assess these characteristics (equations 7.4.5.1 and 7.4.5.2, respectively). The sum of these two quantities is called the reproducibility variance (equation 7.4.5.5). We also examined the functional relationship between precision values and the mean level for each of the target level samples, using ISO 5725-2:1994(E) following section 7.

5. It is not unusual for the repeatability (Sr) and reproducibility (SR) variances to follow a linear relationship with the mean values, often through the origin. We tested whether an intercept other than the origin was needed, and we excluded the intercept in the model if it was deemed nonsignificant. In examining precision according to ISO 5725-2:1994(E), we first obtained an overview of the data, using Mandel��s h and k charts before more detailed analyses. The statistic h is calculated for each participant laboratory and pool combination by a standardization of the mean of the replicate measurements for each laboratory/pool. The average of the replicates for all laboratories reporting on the pool is subtracted and the difference is divided by the standard deviation, again calculated over all participants for the given pool.

Note that h is either positive or negative when the laboratory obtains, on the average, a value higher (or lower) than the average of all laboratories for the given pool. A plot was made for all the h values for all pools, arranged by laboratories. The statistic k measures the relative variability between the GSK-3 replicate measurements of any laboratory for a given pool.

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