May 11, 2019
Performance standards are used in several ways: to gain FDA approval, to make marketing claims, and to test assays after release for sale that are in routine use.
Using glucose meters as an example…
Endocrinologists, who care for people with diabetes, would be highly suited to writing standards. They are in a position to know the magnitude of error that will cause an incorrect treatment decision.
FDA would also be suited with statisticians, biochemists, and physicians.
Companies through their regulatory affairs people know their systems better than anyone, although one can argue that their main goal is to create a standard that is as least burdensome as possible.
So in the case of glucose meters, at least for the 2003 ISO 15197 standard, regulatory affairs people ran the show.
May 8, 2019
The article, “Getting More Information From Glucose Meter Evaluations” has just been published in the Journal of Diabetes Science and Technology.
Our article makes several points. In the ISO 15197 glucose meter standard (2013 edition), one is supposed to prepare a table showing the percentage of results in system accuracy within 5, 10, and 15 mg/dL. Our recommendation is to graph these results in a mountain plot – it is a perfect example of when a mountain plot should be used.
Now I must confess that until we prepared this paper, I had not read ISO 15197 (2013). But based on some reviewer comments, it was clear that I had to bite the bullet, send money to ISO and get the standard. Reading it was an eye opener. The accuracy requirement is:
95% within ± 15 mg/dL (< 100 mg/dL) and within ± 15% (> 100 mg/dL) and
99% within the A and B zones of an error grid
I knew this. But what I didn’t know until I read the standard is user error from the intended population is excluded from this accuracy protocol. Moreover, even the healthcare professionals performing this study could exclude any result if they thought they made an error. I can imagine how this might work: That result can’t be right…
In any case, as previously mentioned in this blog, in the section when users are tested, the requirement for 99% of the results to be within the A and B zones of an error grid was dropped.
In the section where results may be excluded, failure to obtain a result is listed since if there’s no result, you can’t get a difference from reference. But there’s no requirement for the percentage of times a result can be obtained. This is ironic since section 5 is devoted to reliability. How can you have a section on reliability without a failure rate metric?
March 29, 2019
My colleague and I sang the praises of error grids as a way to specify performance – for any assay. To recall, here are some of the benefits:
- Unlike most specifications, the limits can change with concentration
- Unlike most specifications, the limits need not be symmetrical
- Most specifications have one set of limits, implying that results within limits cause no harm and results outside of limits cause harm. Error grid have multiple sets of limits – called zones – whereby harm can be none, minor, or major.
- Error grid zones account of 100% of the results – they cover the XY space of candidate assay vs reference assay. Most specifications cover 95% or 99% of results, leaving the balance unspecified.
Krouwer JS and Cembrowski GS Towards more complete specifications for acceptable analytical performance – a plea for error grid analysis. Clinical Chemistry and Laboratory Medicine, 2011;49:1127-1130.
March 23, 2019
A recent editorial disagrees with the proposed CLIA limits for HbA1c provided by CMS and CDC (The Need for Accuracy in Hemoglobin A1c Proficiency Testing: Why the Proposed CLIA Rule of 2019 Is a Step Backward) online in J Diabetes Science and Technology. The proposed CLIA limits are ± 10% – the NGSP limits are 5%, and the CAP limits 6%. Reading the Federal Register, I don’t understand the basis of the 10%.
This reminds me of another CMS decree in the early 2000s – Equivalent Quality Control. Under this program, a lab director could run quality control for 10 days as well as the automated internal quality checks and decide whether the two were equivalent. If the answer was yes, the frequency of quality control could be reduced to once a month. This made no sense!
March 1, 2019
Another article about Theranos deplores the lack of laboratory medicine input. It does review articles which doubted Theranos. But nowhere, including the above article, do I see anyone questioning that four previous AACC presidents joined the Theranos board. This is laboratory medicine input and IMHO in a bad way.