A little more on the glucose standard ISO 15197 and total error

EP21 is a CLSI standard on total error, which predated the ISO glucose standard. Although I advocated the use of total error 10 years earlier, EP21 was the first standard. As the ISO glucose standard was being prepared, the authors could choose traditionally based limits or total error.

Traditional based limits specify average bias and imprecision and total error as the average bias ± twice the imprecision. This underestimates total error by neglecting random patient interferences.

EP21 simply looks at the differences between the candidate and comparative method. It will slightly overestimate total error since the imprecision of the comparative method will be included in the total error estimate. The overestimate can be minimized by using the average of replicates of the comparative method.

I was asked to attend a meeting of ISO 15197 to answer questions about total error as estimated by EP21. Hence, this is why I know a bit about the ISO glucose standard. Although I can’t say why the EP21 method of estimating total error was used, EP21 will provide wider limits than traditional based limits. Now if you are a regulatory affairs person within industry, this is good.

One thing that EP21 was clear about is reproduced here.

An additional consideration is the relationship between outliers and total analytical error (measurement error). In this document, outliers are considered values beyond predefined limits. Typically, these limits will be wider than total analytical error limits. Note that this definition means that results that are not detached from a distribution might still be considered outliers. To evaluate outliers, one estimates the rate at which they occur. To pass an outlier goal, the observed rate must be below the specified rate. Table 1 shows the possible outcomes of a study to evaluate total analytical error and outliers.

Table 1. Evaluation Results for Total analytical error and Outliers

 Case Evaluation of Total Analytical Error Evaluation of Outliers 1 Pass Pass 2 Pass Fail 3 Fail Pass 4 Fail Fail

So this is much like an error grid. The problem with ISO 15197 is they used total error from EP21 without mentioning the problem of outliers.