A laboratory accredited through the CAP Laboratory Accreditation Program is inspected against the CAP checklists rather than against the regulation directly. The checklists carry the CLIA requirements for introducing a new method — the four or seven characteristics covered in what CLIA requires before you report a result — and then add to them.
The practical difference is not the length of the initial list. Several CAP requirements recur. A CLIA verification is finished when the method goes live. AMR verification repeats twice a year, per analyte, indefinitely. For a chemistry laboratory running a few dozen analytes that is a continuing workload. Laboratories underestimate it more often than any other part of accreditation.
One caution before the detail. Checklist requirements are revised between editions, and they differ by discipline. Treat what follows as an orientation to what the studies are and how to analyse them, then check the current checklist for your own discipline for the wording that applies to you.
The two terms are routinely used as though they were interchangeable. The confusion is understandable because the experimental procedure is often the same. They answer different questions.
Calibration verification asks whether the calibration still holds. Do materials of known concentration, run as patient samples, still recover their assigned values? It is a check on the calibration itself.
AMR verification asks whether the method still recovers correctly across the whole analytical measurement range. That is the range it can measure directly, without dilution or concentration. AMR verification is a check on the range rather than on the calibration. That is why low, mid and high materials are used instead of a single level. See analytical measurement range and reportable range for how that range is set in the first place.
The distinction matters when you come to the analysis, because they are judged differently. Calibration verification is a recovery question at each level. AMR verification is a question about the relationship across levels. That is why a linearity study is the natural analysis and why the deviation from linearity at each level is what you compare against your allowable limit.
Under the CAP chemistry and toxicology checklist, laboratories verify the AMR at least every six months, and also when changes are made to an assay without recalibration. That is the baseline expectation.
There is a useful exemption. A separate AMR verification is not required where the laboratory already calibrates, or verifies calibration, at least every six months using material spanning the low, mid and high points of the range. The calibration work has already answered the question. Laboratories that calibrate frequently can therefore avoid duplicating the study, provided the materials genuinely span the range. A calibration at two levels near the middle does not span it, whatever its frequency.
Requirements differ by discipline. Coagulation tests based on direct measurement of an analyte, those measuring activity or concentration by enzyme immunoassay, immunoturbidity or chromogenic methods, require AMR verification. Clot-based tests do not. Linearity studies are not required for the calibration and calibration verification of CBC instruments. Check the checklist for the discipline you are inspected under rather than generalising from chemistry.
The second recurring requirement catches laboratories with more than one analyser. Instruments measuring the same analyte must be checked against each other at least twice a year for comparability of results. That applies whether the analyte is measured on two instruments of the same model or by two different methods.
This is a different question from the method comparison you ran at bring-up. The acceptance criteria are different, and the analysis is easy to get wrong. Comparing instruments within one laboratory covers it in full.
As with CLIA, the checklist tells you the study is required and how often, not what result passes. The laboratory defines the acceptance criteria, and has to be able to justify them.
For AMR verification the criterion is the allowable deviation from the expected value at each level. It should come from the same place as the rest of your performance specifications: an allowable total error figure, or a specification derived from biological variation. Deriving it from what the instrument happens to achieve is circular. A drifting method will pass a criterion set by its own drift.
The material has to behave like a patient sample in the method, or the recovery you measure is a property of the material rather than of the assay. This is the commutability problem, and it applies as much to a linearity set as to a reference material. Routine quality control material is generally not suitable for verifying calibration unless the manufacturer specifically designates it for that purpose.
The levels should span the AMR rather than cluster in the middle, and should include points near each end, since the ends are where recovery fails first. Where the method is used near a clinical decision point, a level near that point is worth including even if it falls in the middle of the range.
Download the CLSI EP06-A linearity example workbook (.xlsx) — recovery across the measuring interval with deviation from linearity assessed against an allowable limit, the analysis an AMR verification rests on, ready to open in the Analyse-it trial.
The example workbook is downloading.
It opens in Excel on its own — the data and the finished results are both in it. Analyse-it is what lets you change the analysis and re-run it, try the same study on your own data, or work through it to see how the software handles it.
Every feature from all five editions for 15 days.
Treating calibration verification and AMR verification as one requirement. They answer different questions. The exemption works in one direction only: spanning calibration can satisfy AMR verification, but a single-level calibration check does not.
Materials that do not span the range. Three levels clustered near the middle verify the middle. The ends of the interval are what the study exists to check.
Using QC material for calibration verification. Unless the manufacturer designates it for that purpose, routine control material is generally unsuitable, and a non-commutable material gives a recovery that says nothing about patient samples.
Setting the limit from the instrument’s own performance. The allowable deviation has to come from a clinical or biological requirement. A criterion derived from observed scatter will be met by definition.
Forgetting the second analyser. Comparability across instruments is its own twice-yearly requirement, and running AMR verification on each instrument separately does not answer it.
Analyse-it produces the analyses a CAP AMR verification and the twice-yearly instrument check rest on, inside Excel:
Every feature from all five editions for 15 days. Linearity and method comparison are in the Method Validation and Ultimate editions, from US$ 475 a year. Validated against NIST and CLSI reference datasets. For the bring-up requirements these sit on top of, start at what CLIA requires before you report a result; for the twice-yearly check, see comparing instruments within one laboratory.