Questions

We had hundreds of participants at the Westgard Zoom on Linearity and Reportable Range. And many questions raised that couldn't be answered during the time of the call. So here are the answers we couldn't give during the zoom.

 Questions and Answers from the "Toeing the Line" Westgard Zoom

March 2022
Sten Westgard, MS

"Toeing the Line", the Westgard Zoom on the Linearity / Reportable Range study, had a great attendance and spurred many questions. We weren't able to answer them all in the time alotted, but we kept track, and we've got some answers now.

The question that was asked the most was about all the different terms that get used in the linearity and reportable range study.

Q: Reportable Range, Linearity and Analytical Measurement Range (AMR) - do they mean the same thing?

A: Mostly yes, but also a bit no. Linearity was the original term used for these studies, because most of the tests needing verification and validation in the early days of laboratory medicine were, in fact, linear and could plot linear regression lines. However, as laboratory methods have evolved, some tests have emerged that don’t actually have a linear range. The regulations, seeking to include both linear and non-linear range tests, adopted the term Reportable Range. A Reportable Range, in other words, does not necessarily have to be linear. The term Analytical Measurement Range (AMR) is of even more recent coinage, and generally refers to the actual results that the method can measure directly (without dilution or other alteration to the patient sample). AMR was made popular through the CAP accreditation guidelines. There is a further term, Clinical Reportable Range (CRR), which represents the range that can be reported when you take dilution, concentration or other pre-treatment steps of the sample into account. However, CRR is not often referenced anymore, it has fallen out of favor in CAP terminology.

Q: Is it true that if your analyte calibration has more than 3 levels, you don't have to perform a verification every 6 months?

A: This question refers to CLIA regulations, that note if you are doing a calibration verification with more than 3 levels more often than 6 months, you do not have to do another separate reportable range verification every 6 months. If your calibration verification has less than 3 levels, however, you must do a separate reportable range verification at least every 6 months.

So calibration verification can kill two birds with one study - you verify calibration and you verify the reportable range. But that assumes the calibration verification kit has at least 3 levels and that it covers the full reportable range. When you think about calibrators, they should cover the reportable range, but in some cases they may not get both the high and low ends, therefore you would still need to run a separate reportable range study. Also, please note that the reverse is not true. A reportable range verification cannot substitute for a calibration verification.

Q: If after major maintenance i run QC 5 times and there is nothing changed in the performance should I still do Repotable range verification?

A: This question tackles one of the regulatory provisions that requires laboratories to re-verify the range after a complete change of reagents - but there is an ambiguous clause that says if you can prove patients weren't affected you don't have to do it after all. So how does one prove there was no change to patients? Running QC a few times can't really tell you that. You need to do some sort of patient testing, using samples run on the previous lot and then run on the new lot, comparing the differences (of course you need to set some sort of allowable difference, which is completely unaddressed in the regulations.) In this specific case, running of 5 QCs does not fulfill the requirements of a verification of reportable range, you should do something more. Either run patient samples and "prove" there is no difference, or do a reportable range verification study.

Q: If a commercial standard exceeds the AMR of the instrument and must be diluted to a value within range, how would the recovery affect the evaluation of the reportable range?

A: You would need to reliably verify the dilution value - perform the dilution multiple times and measure it multiple times, and then you could include this as an extension of the reportable range. Note that under strict terminology, that extension is not part of the AMR but part of the reportable range or CRR.

Q: When the TEa table shows [performance specification] as +/- 3 SD, where do you get the SD value from?  Proficiency testing performance, QC, other?  And is it average SD of all levels or samples?

The reason this comes up in reportable range is the need to create acceptability standards, which inevitably derive from other quality goals, typically in the form of the allowable total error (TEa), and commonly found in PT/EQA programs. This specific question is narrower still, because it highlights the small set of tests that don't have a specific units or percentage-based specification, but instead have an SD specification. This specification of SD is not meant for an individual SD of a single laboratory, but rather the group sd found in a PT/EQA survey. When the CLIA or CAP (or other PT survey) states a goal of  +/- 3 SD, for example (this is the most common statement for goals of this type), it means that you take the group SD from the PT survey (do NOT take your own SD), and convert that - at your particular level of interest - into a unit or percentage based goal. Then you can go ahead and take a fraction of that as your allowable deviation from linearity.

Thanks again to all who attended the Westgard Zoom on Reportable Range and all those who posed questions.

Stay tuned for more zooms in the future.