The CLSI document EP19

February 6, 2015

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I had occasion recently to see a final draft of CLSI EP19 – which is a framework for using CLSI evaluation documents. I may review this when it is officially released but here are three comments.

  1. There is a cause and effect diagram in EP19 listing assay attributes (precision, interferences, and so on) and the CLSI documents that are used to evaluate these attributes. I published (1) a diagram in 1992 (attributes only) and later adapted my diagram to include the associated CLSI documents and this diagram appeared in a 2002 publication (2). In 2005, I proposed to CLSI that the diagram appear in all CLSI evaluation standards – it is in EP10, EP18, and EP21 although it is not in more recent documents. Now I know that CLSI is a consensus organization whereby documents are a collaborative effort and my diagram has been modified further but there should be a citation to my prior work and there isn’t.
  2. In the clinical performance section, there is no mention of error grids (EP27). In fact, a search of EP19 shows that EP27 is never mentioned. This is most strange. After all, error grids are used to determine if an assay is good enough which is the whole point of an evaluation! Error grids are part of the FDA CLIA waiver recommended guideline and fundamental in glucose meter evaluations. I don’t understand how in years of document development of EP19, EP27 has received zero mention. I did check the list of CLSI publications on their website to make sure that EP27 is still for sale.
  3. There is mention that assay claims should clear – that’s it! no more details are given. Sadly, there was an entire document about uniformity of claims (EP11) that was killed by CLSI management after one manufacturer threatened to quit.

References

  1. Krouwer JS Estimating Total Analytical Error and Its Sources: Techniques to Improve Method Evaluation. 1192, Arch Pathol Lab Med., 116, 726-731.
  2. Krouwer JS Setting Performance Goals and Evaluating Total Analytical Error for Diagnostic Assays. Clin. Chem., 48: 919-927 (2002).

It’s up to the lab director – not really

February 4, 2015

post flight cirrusedp copy

I have previously commented that many CLSI evaluation standards at some point ask the question “is the assay performance good enough” and answer that question with “it’s up to the lab director.”

The problem is that lab directors are not clinicians and do not treat patients. Note that most lab directors are either PhD clinical chemists or pathologists and although pathologists are MDs, they are not clinicians because they do not treat patients.

Of course, lab directors do have a great deal of knowledge about assay performance but in my experience – especially in working on CLSI standards – lab directors tend to focus on analytical errors whereas only total error is of importance to clinicians and the source of errors that contribute to total error is a combination of analytical, pre- and post-analytical error.

So how should the “is it good enough” question be answered? An example appeared recently in the literature (1) where clinicians were surveyed as to what size glucose meter errors would start to cause problems for diabetics under several scenarios. The results provided limits for a glucose meter error grid. Note that there was no attempt to identify error limit sources – the limits simply reflect the observed error, regardless of its source.

Reference

  1. Klonoff DC, Lias C, Vigersky R, et al The surveillance error grid. J Diabetes Sci Technol. 2014;8:658-672.